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BACKGROUND• Antigen-speci� c T-cell activation is regulated by a balance of co-stimulatory and co-inhibitory signals, such as
those mediated by inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) (Figure 1).1
• Binding of these receptors to their ligands results in impaired T-cell function. For these reasons, antibody blockade of PD-1 and CTLA-4 has been identi� ed as a therapeutic modality to reinvigorate or induce tumor-speci� c T-cell immunity.1
Figure 1. Overview of Pathways Affected by CTLA-4 and PD-1CTLA-4 Inhibition PD-1 Inhibition
• In clinical trials, the combined inhibition of PD-1 and CTLA-4 pathways by blocking receptor-ligand interactions has resulted in objective clinical response and increased survival in several solid tumor indications, including melanoma and non-small cell lung carcinoma. As a result, ipilimumab (anti–CTLA-4) in combination with nivolumab (anti–PD-1) has been approved as a � rst line of treatment in patients with metastatic melanoma and is currently being tested in multiple other indications.2-4
• Agenus’ proprietary antibodies, AGEN2034 (anti–PD-1 human IgG4 monoclonal antibody) and AGEN1884 (anti–CTLA-4 human IgG1 monoclonal antibody) are currently under evaluation as monotherapy in phase 1/2 studies in subjects with advanced tumors (NCT03104699 and NCT02694822, respectively).
• A phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, and biological and clinical activity of AGEN1884 in combination with AGEN2034 in patients with metastatic or locally advanced solid tumors is currently ongoing (C550-01; ACTRN12618000003279; NCT03495882).
OBJECTIVE• The objective of this study is to assess safety and tolerability of AGEN1884 in combination with AGEN2034 in
patients with advanced/refractory solid tumors, with expansion into select solid tumors.
METHODS• This is an ongoing phase 1/2, open-label, study of AGEN1884 in combination with AGEN2034 in subjects with
advanced solid tumors, including cervical cancer.
• The study consists of 2 phases: – Phase 1: Dose escalation (focus of this poster) – Phase 2: Expansion in select tumors (ongoing)
• Phase 1 consisted of a standard 3+3 dose escalation with the following escalating dose levels and schedules: – AGEN2034 1 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
– AGEN2034 3 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
• AGEN2034 was administered IV over 60 min and AGEN1884 IV over 90 mins. AGEN1884 was to be administered on the same day as AGEN2034 ≥30 min after the completion of AGEN2034 administration.
• Dose escalation will continue until AGEN2034 3 mg/kg + AGEN1884 1 mg/kg (maximum combination dose level) is shown to be safe or the maximum tolerated dose (de� ned as the combination below which ≥33% of subjects develop dose-limiting toxicities [DLTs]) is reached.
• A schematic of the phase 1 dose-escalation design is presented in Figure 2.
Figure 2. Dose-Escalation Study Flow
Starting dose
Treat 3 patients;Assess DLTs after 3 weeks
Number ofDLTs
No
Yes
≤1 of 6
0 of 3 ≥2 of 3
≥2 of 6
1 of 3
1 of 3
Treat additional 3 patients;Assess DLTs after 3 weeks
Number of DLTs
MTD/maximum CDL to be con�rmed on total
of 6 patients
Initiate phase 2 at maximum planned CDL
or MTD
Determine MTDEscalate to next CDL
Maximum CDL per protocol?
Determine MTD
CDL, combination dose level; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
• Each subject will receive the combination treatment for a maximum of 24 months or until con� rmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products occurs.
– Patients who do not complete the DLT observation period of 21 days after the � rst dose, for reasons other than a DLT, will be replaced.
– Cohorts will be back� lled to 10 subjects once they have reached DLT or MTD.
• Eligible patients include adults (aged ≥18 years) with a histologically or cytologically con� rmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• The treatment phase was divided into 6-week cycles, each beginning with the combined administration of AGEN2034 and AGEN1884 on day 1. Thereafter, AGEN2034 will be administrated q2w, completing the 6-week cycle.
– Tumor assessments are to be conducted at 6, 12, and 18 weeks from � rst dose, and every 9 weeks thereafter until disease progression is con� rmed or a new line of therapy is initiated.
• Phase 1 endpoints: – Primary: Occurrence of DLTs in patients in dose escalation during the � rst 21 days of treatment – Secondary:
Con� rmed best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as determined by the investigator
Frequency and nature of treatment-emergent adverse events (TEAEs) Pharmacokinetic pro� le and immunogenicity of AGEN1884 and AGEN2034
RESULTS • As of July 16, 2018, the study was ongoing, though total enrollment was achieved in the phase 1 portion
(ie, 10 patients in each dose cohort). Data are preliminary as it is being cleaned and/or collected at this time.
• Five patients had discontinued from the study treatment prior to data extract: – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=1; investigator decision, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=3
• There was 1 death not related to the study (66-year-old female with lung cancer treated with AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w died due to disease progression).
• Patients were Caucasian (100%) and primarily female (75%), with a median of 2.3 months from the most recent recurrence/progression to the administration of the � rst combination dose (Table 1).
• The cancer types for the 20 patients were as follows: breast cancer (triple negative, n=2; with lung metastases, n=1; with dermal lymphatics, n=1), ovarian cancer (n=2), mesothelioma (pleural, n=1; peritoneal, n=1), squamous carcinoma of head and neck (tongue; n=1), anal squamous carcinoma (n=1), pleomorphic soft tissue sarcoma (n=1), lung cancer (n=1), metastastic leiomyosarcoma (n=1), advanced gastrointestinal stromal tumor (n=1), rhabdomyosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), recurrent chordoma of the thoracic spine (n=1), chordoma (n=1), colorectal-rectal (n=1), esophageal adenocarcinoma (n=1).
Table 1. Demographics and Baseline Characteristics (Safety Set) AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Age (years)
Mean (SD) 58.4 (8.13) 47.6 (19.68) 53.0 (15.66)
Min, Max 43, 69 21, 79 21, 79
Female, n (%) 8 (80%) 7 (70%) 15 (75%)
BMI (kg/m2)
Mean (SD) 28.71 (8.227) 27.48 (7.006) 28.10 (7.464)
Min, Max 18.8, 40.9 20.9, 45.5 18.8, 45.5
ECOG performance status, n (%)
0 5 (50%) 7 (70%) 12 (60%)
1 5 (50%) 3 (30%) 8 (40%)
Time between most recent progression and � rst dose date (months)
n 6 6 12
Mean (SD) 2.26 (1.665) 2.34 (1.002) 2.30 (1.311)
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group.
• An overview of safety and tolerability is presented in Table 2.
Table 2. Overview of Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Any TEAE 10 (100%) 9 (90%) 19 (95%)
Any serious TEAE 3 (30%) 2 (20%) 5 (25%)
Any grade ≥3 TEAE 3 (30%) 2 (20%) 5 (25%)
Any immune-related TEAE 5 (50%) 4 (40%) 9 (45%)
Any treatment-related TEAE 8 (80%) 7 (70%) 15 (75%)
Any treatment-related serious TEAE 1 (10%) 2 (20%) 3 (15%)
Any treatment-related grade ≥3 TEAE 0 2 (20%) 2 (10%)
TEAE, treatment-emergent adverse event.
• As of July 16, 2018, no DLTs have been observed, and none of the TEAEs led to discontinuation or death.
• TEAEs were reported in 19 of 20 patients (95%), with the most common MedDRA version 18.1 preferred terms listed in (Table 3).
• Most TEAEs were mild to moderate in severity (grade 1 or 2); 5 patients experienced TEAEs of grade ≥3. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Vomiting, n=1; wound and cancer pain, n=1; hypotension, n=1
– AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection and pneumonia, n=1; pulmonary embolism, n=1
– Of these, the events of lower respiratory tract infection and pulmonary embolism were considered related to study treatment by the investigator.
Table 3. Most Common* Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Fatigue 5 (50%) 5 (50%) 10 (50%)
Nausea 3 (30%) 4 (40%) 7 (35%)
Pruritus 2 (20%) 3 (30%) 5 (25%)
Chills 3 (30%) 1 (10%) 4 (20%)
Vomiting 2 (20%) 2 (20%) 4 (20%)
Back pain 4 (40%) 0 4 (20%)*Occurring in ≥20% of patients.
• Serious TEAEs occurred in 5 patients: 3 receiving AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w and 2 receiving AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w
• 3 patients experienced serious TEAEs considered related to study treatment. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Diarrhea, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection, n=1; pulmonary embolism, n=1
• The summary of best overall response is listed in Table 4.
• The partial response was ongoing in one of the women with metastatic ovarian cancer. For patients with >90 days of treatment, stable disease was ongoing for 1 female with breast cancer (with lung metastases), 1 female with metastatic ovarian cancer, and 1 male with pleomorphic soft tissue sarcoma (with lung metastases).
Table 4. Summary of Best Overall Response at Time of Data Cut-off
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Complete response 0 0 0
Partial response 1 0 1
Stable disease 5 1 6
Progressive disease 3 6 9
Not evaluable 1 0 1
Pending 0 3 3Overall response determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
DISCUSSION• In the phase 1 portion, which is still ongoing, preliminary results demonstrate that AGEN1884 (1 mg/kg q6w) +
AGEN2034 (3 mg/kg q2w) is generally safe, well tolerated, and active in adults with select advanced/refractory solid tumors.
• The phase 2 portion of this study evaluating AGEN1884 in combination with AGEN2034 in adults with second-line cervical cancer and other solid tumors is ongoing.
– The phase 2 recommended dosing was determined as AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w.
References1. Topalian SL, Drake CG, Pardoll DM. Cancer Cell. 2015;27(4):450-61.2. Hodi FS, Chesney J, Pavlick AC, et al. Lancet Oncol.
2016;17(11):1558-68.
3. Antonia SJ, López-Martin JA, Bendell J, et al. Lancet Oncol. 2016;17(7):883-95.
4. Hellmann MD, Gettinger SN, Goldman JW, et al. J Clin Oncol. 2016;34(15 suppl):3001.5
Disclosures CD Dupont, AM Gonzalez, M Lim, D Savitsky, M Carini, S Hu, O Shebanova, E Dow, W Ortuzar, JS Buell, RB Stein, H Youssou� an: Agenus Inc.: current or former employment/consultancy and stock ownership.
Acknowledgments The authors thank Nicole Coolbaugh of The Medicine Group, LLC (New Hope, PA, USA) for providing medical writing and editorial support, which was funded by Agenus Inc. (Lexington, MA, USA) in accordance with Good Publication Practice guidelines. The licensed antibodies AGEN2034 and AGEN1884 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. Recepta Biopharma S.A. has exclusive rights to these antibodies in Brazil and � ve other South American countries.
Funding This study was funded by Agenus Inc. (Lexington, MA, USA).
CorrespondenceWaldo Ortuzar: [email protected]
Presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO), October 19–23, 2018, in Munich, Germany
Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors
Jermaine Coward,1 Charlotte Lemech,2 Tarek Meniawy,3 Christopher D. Dupont,4 Ana M. Gonzalez,4 Min Lim,4 David Savitsky,4 Meg Carini,4 Shuang Hu,4 Olga Shebanova,4 Ed Dow,4
Waldo Ortuzar,4 Jennifer S. Buell,4 Robert Benjamin Stein,4 Hagop Youssou� an4
1Icon Cancer Center, South Brisbane, Australia; 2Scientia Clinical Research, Sydney, Australia; 3Linear Clinical Research, Perth, Australia; 4Agenus Inc. or subsidiary thereof (current or former employee), Lexington, MA, USA
1168P
BACK
GROU
ND•
Ant
igen
-spe
ci� c
T-c
ell a
ctiv
atio
n is
regu
late
d b
y a
bal
ance
of c
o-st
imul
ator
y an
d c
o-in
hibi
tory
sig
nals
, suc
h as
th
ose
med
iate
d by
inhi
bito
ry re
cep
tors
cyt
otox
ic T
-lym
pho
cyte
–ass
ocia
ted
antig
en 4
(CTL
A-4
) and
pro
gram
med
ce
ll de
ath
pro
tein
-1 (P
D-1
) (Fi
gur
e 1)
.1
• B
indi
ng o
f the
se re
cept
ors
to th
eir
ligan
ds re
sults
in im
paire
d T
-cel
l fun
ctio
n. F
or th
ese
reas
ons,
ant
ibod
y bl
ocka
de o
f PD
-1 a
nd C
TLA
-4 h
as b
een
iden
ti� e
d a
s a
ther
apeu
tic m
odal
ity to
rein
vigo
rate
or
indu
ce
tum
or-s
pec
i� c
T-ce
ll im
mun
ity.1
Fig
ure
1. O
verv
iew
of
Pat
hway
s A
ffec
ted
by
CT
LA-4
and
PD
-1C
TLA
-4 In
hib
itio
nP
D-1
Inhi
bit
ion
• In
clin
ical
tria
ls, t
he c
omb
ined
inhi
biti
on o
f PD
-1 a
nd C
TLA
-4 p
athw
ays
by
blo
ckin
g re
cep
tor-
ligan
d
inte
ract
ions
has
res
ulte
d in
ob
ject
ive
clin
ical
res
pon
se a
nd in
crea
sed
sur
viva
l in
seve
ral s
olid
tum
or
indi
catio
ns, i
nclu
din
g m
elan
oma
and
non-
smal
l cel
l lun
g ca
rcin
oma.
As
a re
sult,
ipili
mum
ab (a
nti–
CTL
A-4
) in
com
bin
atio
n w
ith n
ivol
umab
(ant
i–P
D-1
) has
bee
n ap
pro
ved
as
a � r
st li
ne o
f tre
atm
ent
in p
atie
nts
with
m
etas
tatic
mel
anom
a an
d is
cur
rent
ly b
eing
tes
ted
in m
ultip
le o
ther
ind
icat
ions
.2-4
• A
genu
s’ p
rop
rieta
ry a
ntib
odie
s, A
GE
N20
34 (a
nti–
PD
-1 h
uman
IgG
4 m
onoc
lona
l ant
ibod
y) a
nd A
GE
N18
84
(ant
i–C
TLA
-4 h
uman
IgG
1 m
onoc
lona
l ant
ibod
y) a
re c
urre
ntly
und
er e
valu
atio
n as
mon
othe
rap
y in
pha
se 1
/2
stud
ies
in s
ubje
cts
with
ad
vanc
ed t
umor
s (N
CT0
3104
699
and
NC
T026
9482
2, r
esp
ectiv
ely)
.
• A
pha
se 1
/2, o
pen
-lab
el, m
ulti-
arm
tria
l to
inve
stig
ate
the
safe
ty, t
oler
abili
ty, p
harm
acok
inet
ics,
and
bio
logi
cal
and
clin
ical
act
ivity
of A
GE
N18
84 in
com
bin
atio
n w
ith A
GE
N20
34 in
pat
ient
s w
ith m
etas
tatic
or
loca
lly
adva
nced
sol
id t
umor
s is
cur
rent
ly o
ngoi
ng (C
550-
01; A
CTR
N12
6180
0000
3279
; NC
T034
9588
2).
OBJE
CTIV
E•
The
obje
ctiv
e of
thi
s st
udy
is t
o as
sess
saf
ety
and
tol
erab
ility
of A
GE
N18
84 in
com
bin
atio
n w
ith A
GE
N20
34 in
p
atie
nts
with
ad
vanc
ed/r
efra
ctor
y so
lid t
umor
s, w
ith e
xpan
sion
into
sel
ect
solid
tum
ors.
MET
HODS
• Th
is is
an
ongo
ing
pha
se 1
/2, o
pen
-lab
el, s
tud
y of
AG
EN
1884
in c
omb
inat
ion
with
AG
EN
2034
in s
ubje
cts
with
ad
vanc
ed s
olid
tum
ors,
incl
udin
g ce
rvic
al c
ance
r.
• Th
e st
udy
cons
ists
of 2
pha
ses:
–P
hase
1: D
ose
esca
latio
n (fo
cus
of t
his
pos
ter)
–P
hase
2: E
xpan
sion
in s
elec
t tu
mor
s (o
ngoi
ng)
• P
hase
1 c
onsi
sted
of a
sta
ndar
d 3
+3
dos
e es
cala
tion
with
the
follo
win
g es
cala
ting
dos
e le
vels
and
sch
edul
es:
–A
GE
N20
34 1
mg/
kg a
dm
inis
tere
d e
very
2 w
eeks
(q2w
) in
com
bin
atio
n w
ith A
GE
N18
84 1
mg/
kg
adm
inis
tere
d e
very
6 w
eeks
(q6w
) –A
GE
N20
34 3
mg/
kg a
dm
inis
tere
d e
very
2 w
eeks
(q2w
) in
com
bin
atio
n w
ith A
GE
N18
84 1
mg/
kg
adm
inis
tere
d e
very
6 w
eeks
(q6w
)
• A
GE
N20
34 w
as a
dm
inis
tere
d IV
ove
r 60
min
and
AG
EN
1884
IV o
ver
90 m
ins.
AG
EN
1884
was
to
be
adm
inis
tere
d o
n th
e sa
me
day
as
AG
EN
2034
≥30
min
aft
er t
he c
omp
letio
n of
AG
EN
2034
ad
min
istr
atio
n.
• D
ose
esca
latio
n w
ill c
ontin
ue u
ntil
AG
EN
2034
3 m
g/kg
+ A
GE
N18
84 1
mg/
kg (m
axim
um c
omb
inat
ion
dos
e le
vel)
is s
how
n to
be
safe
or
the
max
imum
tol
erat
ed d
ose
(de�
ned
as
the
com
bin
atio
n b
elow
whi
ch ≥
33%
of
sub
ject
s d
evel
op d
ose-
limiti
ng t
oxic
ities
[DLT
s]) i
s re
ache
d.
• A
sch
emat
ic o
f the
pha
se 1
dos
e-es
cala
tion
des
ign
is p
rese
nted
in F
igur
e 2.
Fig
ure
2. D
ose
-Esc
alat
ion
Stu
dy
Flo
w
Sta
rtin
g d
ose
Trea
t 3
pat
ient
s;A
sses
s D
LTs
afte
r 3
wee
ks
Num
ber
of
DLT
s
No
Yes
≤1 o
f 6
0 of
3≥2
of 3
≥2 o
f 6
1 of
3
1 of
3
Trea
t ad
diti
onal
3 p
atie
nts;
Ass
ess
DLT
s af
ter
3 w
eeks
Num
ber
of
DLT
s
MTD
/max
imum
CD
L to
be
con�
rmed
on
tota
l of
6 p
atie
nts
Initi
ate
phas
e 2
at
max
imum
pla
nned
CD
L or
MTD
Det
erm
ine
MTD
Esc
alat
e to
nex
t C
DL
Max
imum
CD
L p
er p
roto
col?
Det
erm
ine
MTD
CD
L, c
omb
inat
ion
dos
e le
vel;
DLT
, dos
e-lim
iting
tox
icity
; MTD
, max
imum
tol
erat
ed d
ose.
• E
ach
sub
ject
will
rec
eive
the
com
bin
atio
n tr
eatm
ent
for
a m
axim
um o
f 24
mon
ths
or u
ntil
con�
rm
ed d
isea
se
pro
gres
sion
, una
ccep
tab
le t
oxic
ity, o
r an
y cr
iterio
n fo
r w
ithd
raw
al fr
om t
he t
rial o
r th
e in
vest
igat
iona
l med
icin
al
pro
duc
ts o
ccur
s.
–P
atie
nts
who
do
not
com
ple
te t
he D
LT o
bse
rvat
ion
per
iod
of 2
1 d
ays
afte
r th
e � r
st d
ose,
for
reas
ons
othe
r th
an a
DLT
, will
be
rep
lace
d.
–C
ohor
ts w
ill b
e b
ack�
lled
to
10 s
ubje
cts
once
the
y ha
ve r
each
ed D
LT o
r M
TD.
• El
igib
le p
atie
nts
incl
ude
adul
ts (a
ged
≥18
year
s) w
ith a
his
tolo
gica
lly o
r cyt
olog
ical
ly c
on� r
med
dia
gnos
is o
f a
met
asta
tic o
r loc
ally
adv
ance
d so
lid tu
mor
for w
hich
no
stan
dard
ther
apy
is a
vaila
ble
or s
tand
ard
ther
apy
has
faile
d.
• Th
e tr
eatm
ent
pha
se w
as d
ivid
ed in
to 6
-wee
k cy
cles
, eac
h b
egin
ning
with
the
com
bin
ed a
dm
inis
trat
ion
of A
GE
N20
34 a
nd A
GE
N18
84 o
n d
ay 1
. The
reaf
ter,
AG
EN
2034
will
be
adm
inis
trat
ed q
2w, c
omp
letin
g th
e 6-
wee
k cy
cle.
–Tu
mor
ass
essm
ents
are
to
be
cond
ucte
d a
t 6,
12,
and
18
wee
ks fr
om �
rst
dos
e, a
nd e
very
9 w
eeks
th
erea
fter
unt
il d
isea
se p
rogr
essi
on is
con
� rm
ed o
r a
new
line
of t
hera
py
is in
itiat
ed.
• P
hase
1 e
ndp
oint
s: –P
rimar
y: O
ccur
renc
e of
DLT
s in
pat
ient
s in
dos
e es
cala
tion
dur
ing
the
� rst
21
day
s of
tre
atm
ent
–S
econ
dar
y:
C
on� r
med
bes
t ov
eral
l res
pon
se p
er R
esp
onse
Eva
luat
ion
Crit
eria
in S
olid
Tum
ors
(RE
CIS
T) v
1.1,
as
det
erm
ined
by
the
inve
stig
ator
Fr
eque
ncy
and
nat
ure
of t
reat
men
t-em
erge
nt a
dve
rse
even
ts (T
EA
Es)
P
harm
acok
inet
ic p
ro� l
e an
d im
mun
ogen
icity
of A
GE
N18
84 a
nd A
GE
N20
34
RESU
LTS
• A
s of
Jul
y 16
, 201
8, t
he s
tud
y w
as o
ngoi
ng, t
houg
h to
tal e
nrol
lmen
t w
as a
chie
ved
in t
he p
hase
1 p
ortio
n (ie
, 10
pat
ient
s in
eac
h d
ose
coho
rt).
Dat
a ar
e p
relim
inar
y as
it is
bei
ng c
lean
ed a
nd/o
r co
llect
ed a
t th
is t
ime.
• Fi
ve p
atie
nts
had
dis
cont
inue
d fr
om t
he s
tud
y tr
eatm
ent
prio
r to
dat
a ex
trac
t:
–A
GE
N20
34 1
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Pro
gres
sive
dis
ease
, n=
1; in
vest
igat
or d
ecis
ion,
n=
1 –A
GE
N20
34 3
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Pro
gres
sive
dis
ease
, n=
3
• Th
ere
was
1 d
eath
not
rel
ated
to
the
stud
y (6
6-ye
ar-o
ld fe
mal
e w
ith lu
ng c
ance
r tr
eate
d w
ith A
GE
N20
34
1 m
g/kg
q2w
+ A
GE
N18
84 1
mg/
kg q
6w d
ied
due
to
dis
ease
pro
gres
sion
).
• P
atie
nts
wer
e C
auca
sian
(100
%) a
nd p
rimar
ily fe
mal
e (7
5%),
with
a m
edia
n of
2.3
mon
ths
from
the
mos
t re
cent
rec
urre
nce/
pro
gres
sion
to
the
adm
inis
trat
ion
of t
he �
rst
com
bin
atio
n d
ose
(Tab
le 1
).
• Th
e ca
ncer
typ
es fo
r th
e 20
pat
ient
s w
ere
as fo
llow
s: b
reas
t ca
ncer
(trip
le n
egat
ive,
n=
2; w
ith lu
ng
met
asta
ses,
n=
1; w
ith d
erm
al ly
mp
hatic
s, n
=1)
, ova
rian
canc
er (n
=2)
, mes
othe
liom
a (p
leur
al, n
=1;
per
itone
al,
n=1)
, sq
uam
ous
carc
inom
a of
hea
d a
nd n
eck
(tong
ue; n
=1)
, ana
l sq
uam
ous
carc
inom
a (n
=1)
, ple
omor
phi
c so
ft t
issu
e sa
rcom
a (n
=1)
, lun
g ca
ncer
(n=
1), m
etas
tast
ic le
iom
yosa
rcom
a (n
=1)
, ad
vanc
ed g
astr
oint
estin
al
stro
mal
tum
or (n
=1)
, rha
bd
omyo
sarc
oma
(n=
1), a
lveo
lar
rhab
dom
yosa
rcom
a (n
=1)
, rec
urre
nt c
hord
oma
of t
he
thor
acic
sp
ine
(n=
1), c
hord
oma
(n=
1), c
olor
ecta
l-re
ctal
(n=
1), e
sop
hage
al a
den
ocar
cino
ma
(n=
1).
Tab
le 1
. Dem
og
rap
hics
and
Bas
elin
e C
hara
cter
isti
cs (S
afet
y S
et)
AG
EN
2034
1 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
AG
EN
2034
3 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
Tota
l Pat
ien
ts(N
=20
)
Ag
e (y
ears
)
Mea
n (S
D)
58.4
(8.1
3)47
.6 (1
9.68
)53
.0 (1
5.66
)
Min
, Max
43
, 69
21, 7
921
, 79
Fem
ale,
n (%
)8
(80%
)7
(70%
)15
(75%
)
BM
I (kg
/m2 )
Mea
n (S
D)
28.7
1 (8
.227
)27
.48
(7.0
06)
28.1
0 (7
.464
)
Min
, Max
18
.8, 4
0.9
20.9
, 45.
518
.8, 4
5.5
EC
OG
per
form
ance
sta
tus,
n (%
)
05
(50%
)7
(70%
)12
(60%
)
15
(50%
)3
(30%
)8
(40%
)
Tim
e b
etw
een
mo
st r
ecen
t p
rog
ress
ion
and
� rs
t d
ose
dat
e (m
onth
s)
n6
612
Mea
n (S
D)
2.26
(1.6
65)
2.34
(1.0
02)
2.30
(1.3
11)
BM
I, b
ody
mas
s in
dex
; EC
OG
, Eas
tern
Coo
per
ativ
e O
ncol
ogy
Gro
up.
• A
n ov
ervi
ew o
f saf
ety
and
tol
erab
ility
is p
rese
nted
in T
able
2.
Tab
le 2
. Ove
rvie
w o
f Tr
eatm
ent-
Em
erg
ent
Ad
vers
e E
vent
(Saf
ety
Set
)
Pat
ien
ts, n
(%)
AG
EN
2034
1 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
AG
EN
2034
3 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
Tota
l Pat
ien
ts(N
=20
)
Any
TE
AE
10 (1
00%
)9
(90%
)19
(95%
)
Any
ser
ious
TE
AE
3 (3
0%)
2 (2
0%)
5 (2
5%)
Any
gra
de
≥3 T
EA
E3
(30%
)2
(20%
)5
(25%
)
Any
imm
une-
rela
ted
TE
AE
5 (5
0%)
4 (4
0%)
9 (4
5%)
Any
tre
atm
ent-
rela
ted
TE
AE
8 (8
0%)
7 (7
0%)
15 (7
5%)
Any
tre
atm
ent-
rela
ted
ser
ious
TE
AE
1 (1
0%)
2 (2
0%)
3 (1
5%)
Any
tre
atm
ent-
rela
ted
gra
de
≥3 T
EA
E0
2 (2
0%)
2 (1
0%)
TEA
E, t
reat
men
t-em
erge
nt a
dve
rse
even
t.
• A
s of
Jul
y 16
, 201
8, n
o D
LTs
have
bee
n ob
serv
ed, a
nd n
one
of t
he T
EA
Es
led
to
dis
cont
inua
tion
or d
eath
.
• TE
AE
s w
ere
rep
orte
d in
19
of 2
0 p
atie
nts
(95%
), w
ith t
he m
ost
com
mon
Med
DR
A v
ersi
on 1
8.1
pre
ferr
ed
term
s lis
ted
in (T
able
3).
• M
ost
TEA
Es
wer
e m
ild t
o m
oder
ate
in s
ever
ity (g
rad
e 1
or 2
); 5
pat
ient
s ex
per
ienc
ed T
EA
Es
of g
rad
e ≥3
. –A
GE
N20
34 1
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Vom
iting
, n=
1; w
ound
and
can
cer
pai
n, n
=1;
hy
pot
ensi
on, n
=1
–A
GE
N20
34 3
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Low
er r
esp
irato
ry t
ract
infe
ctio
n an
d p
neum
onia
, n=
1;
pul
mon
ary
emb
olis
m, n
=1
–O
f the
se, t
he e
vent
s of
low
er r
esp
irato
ry t
ract
infe
ctio
n an
d p
ulm
onar
y em
bol
ism
wer
e co
nsid
ered
rel
ated
to
stud
y tr
eatm
ent
by
the
inve
stig
ator
.
Tab
le 3
. Mo
st C
om
mo
n* T
reat
men
t-E
mer
gen
t A
dve
rse
Eve
nt (S
afet
y S
et)
Pat
ien
ts, n
(%)
AG
EN
2034
1 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
AG
EN
2034
3 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
Tota
l Pat
ien
ts(N
=20
)
Fatig
ue5
(50%
)5
(50%
)10
(50%
)
Nau
sea
3 (3
0%)
4 (4
0%)
7 (3
5%)
Pru
ritus
2 (2
0%)
3 (3
0%)
5 (2
5%)
Chi
lls3
(30%
)1
(10%
)4
(20%
)
Vom
iting
2 (2
0%)
2 (2
0%)
4 (2
0%)
Bac
k p
ain
4 (4
0%)
04
(20%
)*O
ccur
ring
in ≥
20%
of p
atie
nts.
• S
erio
us T
EA
Es
occu
rred
in 5
pat
ient
s: 3
rec
eivi
ng A
GE
N20
34 1
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
and
2
rece
ivin
g A
GE
N20
34 3
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
• 3
pat
ient
s ex
per
ienc
ed s
erio
us T
EA
Es
cons
ider
ed r
elat
ed t
o st
udy
trea
tmen
t. –A
GE
N20
34 1
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Dia
rrhe
a, n
=1
–A
GE
N20
34 3
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
: Low
er r
esp
irato
ry t
ract
infe
ctio
n, n
=1;
pul
mon
ary
emb
olis
m, n
=1
• Th
e su
mm
ary
of b
est
over
all r
esp
onse
is li
sted
in T
able
4.
• Th
e pa
rtia
l res
pons
e w
as o
ngoi
ng in
one
of t
he w
omen
with
met
asta
tic o
varia
n ca
ncer
. For
pat
ient
s w
ith
>90
day
s of
trea
tmen
t, st
able
dis
ease
was
ong
oing
for 1
fem
ale
with
bre
ast c
ance
r (w
ith lu
ng m
etas
tase
s), 1
fem
ale
with
met
asta
tic o
varia
n ca
ncer
, and
1 m
ale
with
ple
omor
phic
sof
t tis
sue
sarc
oma
(with
lung
met
asta
ses)
.
Tab
le 4
. Sum
mar
y o
f B
est
Ove
rall
Res
po
nse
at T
ime
of
Dat
a C
ut-o
ff
Pat
ien
ts, n
(%)
AG
EN
2034
1 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
AG
EN
2034
3 m
g/k
g +
A
GE
N18
84 1
mg
/kg
(N=
10)
Tota
l Pat
ien
ts(N
=20
)
Com
ple
te r
esp
onse
00
0
Par
tial r
esp
onse
10
1
Sta
ble
dis
ease
51
6
Pro
gres
sive
dis
ease
36
9
Not
eva
luab
le1
01
Pen
din
g0
33
Ove
rall
resp
onse
det
erm
ined
by
Res
pon
se E
valu
atio
n C
riter
ia in
Sol
id T
umor
s (R
EC
IST)
v1.
1.
DISC
USSI
ON•
In t
he p
hase
1 p
ortio
n, w
hich
is s
till o
ngoi
ng, p
relim
inar
y re
sults
dem
onst
rate
tha
t A
GE
N18
84 (1
mg/
kg q
6w) +
A
GE
N20
34 (3
mg/
kg q
2w) i
s ge
nera
lly s
afe,
wel
l tol
erat
ed, a
nd a
ctiv
e in
adu
lts w
ith s
elec
t adv
ance
d/re
frac
tory
so
lid tu
mor
s.
• Th
e p
hase
2 p
ortio
n of
thi
s st
udy
eval
uatin
g A
GE
N18
84 in
com
bin
atio
n w
ith A
GE
N20
34 in
ad
ults
with
se
cond
-lin
e ce
rvic
al c
ance
r an
d o
ther
sol
id t
umor
s is
ong
oing
. –Th
e ph
ase
2 re
com
men
ded
dosi
ng w
as d
eter
min
ed a
s A
GE
N20
34 3
mg/
kg q
2w +
AG
EN
1884
1 m
g/kg
q6w
.
Ref
eren
ces
1. T
opal
ian
SL,
Dra
ke C
G, P
ardo
ll D
M. C
ance
r Cel
l. 20
15;2
7(4)
:450
-61.
2. H
odi F
S, C
hesn
ey J
, Pav
lick
AC
, et
al. L
ance
t O
ncol
. 20
16;1
7(11
):155
8-68
.
3. A
nton
ia S
J, L
ópez
-Mar
tin J
A, B
end
ell J
, et
al. L
ance
t O
ncol
. 20
16;1
7(7)
:883
-95.
4. H
ellm
ann
MD
, Get
tinge
r S
N, G
old
man
JW
, et
al. J
Clin
Onc
ol.
2016
;34(
15 s
upp
l):30
01.5
Dis
clo
sure
s C
D D
upon
t, A
M G
onza
lez,
M L
im, D
Sav
itsky
, M C
arin
i, S
Hu,
O S
heb
anov
a, E
Dow
, W O
rtuz
ar, J
S B
uell,
RB
Ste
in, H
You
ssou
� an:
Age
nus
Inc.
: cu
rren
t or
form
er e
mp
loym
ent/
cons
ulta
ncy
and
sto
ck o
wne
rshi
p.
Ack
now
led
gm
ents
Th
e au
thor
s th
ank
Nic
ole
Coo
lbau
gh o
f The
Med
icin
e G
roup
, LLC
(New
Hop
e, P
A, U
SA
) for
pro
vid
ing
med
ical
writ
ing
and
ed
itoria
l sup
por
t,
whi
ch w
as fu
nded
by
Age
nus
Inc.
(Lex
ingt
on, M
A, U
SA
) in
acco
rdan
ce w
ith G
ood
Pub
licat
ion
Pra
ctic
e gu
idel
ines
. The
lice
nsed
ant
ibod
ies
AG
EN
2034
and
AG
EN
1884
wer
e or
igin
ally
dev
elop
ed u
nder
a C
olla
bor
ativ
e R
esea
rch
and
Dev
elop
men
t A
gree
men
t b
etw
een
Lud
wig
Can
cer
Res
earc
h, 4
-Ant
ibod
y A
G (n
ow A
genu
s S
witz
erla
nd In
c.) a
nd R
ecep
ta B
iop
harm
a S
.A. R
ecep
ta B
iop
harm
a S
.A. h
as e
xclu
sive
rig
hts
to
thes
e an
tibod
ies
in B
razi
l and
� ve
oth
er S
outh
Am
eric
an c
ount
ries.
Fund
ing
Th
is s
tud
y w
as fu
nded
by
Age
nus
Inc.
(Lex
ingt
on, M
A, U
SA
).
Co
rres
po
nden
ceW
ald
o O
rtuz
ar: w
ald
o.or
tuza
r@ag
enus
bio
.com
Pre
sent
ed a
t th
e 20
18 A
nnua
l Con
gres
s of
the
Eur
opea
n S
ocie
ty fo
r M
edic
al O
ncol
ogy
(ES
MO
), O
ctob
er 1
9–23
, 201
8, in
Mun
ich,
Ger
man
y
Pha
se 1
/2 S
tud
y o
f C
TLA
-4 In
hib
ito
r A
GE
N18
84 +
PD
-1 In
hib
ito
r A
GE
N20
34 in
Pat
ient
s W
ith
Ad
vanc
ed/R
efra
cto
ry S
olid
Tum
ors
, W
ith
Exp
ansi
on
Into
Sec
ond
-Lin
e C
ervi
cal C
ance
r an
d S
olid
Tum
ors
Jerm
aine
Co
war
d,1
Cha
rlo
tte
Lem
ech,
2 Ta
rek
Men
iaw
y,3
Chr
isto
phe
r D
. Dup
ont
,4 A
na M
. Go
nzal
ez,4
Min
Lim
,4 D
avid
Sav
itsk
y,4
Meg
Car
ini,4
Shu
ang
Hu,
4 O
lga
She
ban
ova
,4 E
d D
ow
,4
Wal
do
Ort
uzar
,4 Je
nnife
r S
. Bue
ll,4
Ro
ber
t B
enja
min
Ste
in,4
Hag
op
Yo
usso
u� a
n4
1 Ico
n C
ance
r C
ente
r, S
out
h B
risb
ane,
Aus
tral
ia; 2 S
cien
tia
Clin
ical
Res
earc
h, S
ydne
y, A
ustr
alia
; 3 Lin
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BACKGROUND• Antigen-speci� c T-cell activation is regulated by a balance of co-stimulatory and co-inhibitory signals, such as
those mediated by inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) (Figure 1).1
• Binding of these receptors to their ligands results in impaired T-cell function. For these reasons, antibody blockade of PD-1 and CTLA-4 has been identi� ed as a therapeutic modality to reinvigorate or induce tumor-speci� c T-cell immunity.1
Figure 1. Overview of Pathways Affected by CTLA-4 and PD-1CTLA-4 Inhibition PD-1 Inhibition
• In clinical trials, the combined inhibition of PD-1 and CTLA-4 pathways by blocking receptor-ligand interactions has resulted in objective clinical response and increased survival in several solid tumor indications, including melanoma and non-small cell lung carcinoma. As a result, ipilimumab (anti–CTLA-4) in combination with nivolumab (anti–PD-1) has been approved as a � rst line of treatment in patients with metastatic melanoma and is currently being tested in multiple other indications.2-4
• Agenus’ proprietary antibodies, AGEN2034 (anti–PD-1 human IgG4 monoclonal antibody) and AGEN1884 (anti–CTLA-4 human IgG1 monoclonal antibody) are currently under evaluation as monotherapy in phase 1/2 studies in subjects with advanced tumors (NCT03104699 and NCT02694822, respectively).
• A phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, and biological and clinical activity of AGEN1884 in combination with AGEN2034 in patients with metastatic or locally advanced solid tumors is currently ongoing (C550-01; ACTRN12618000003279; NCT03495882).
OBJECTIVE• The objective of this study is to assess safety and tolerability of AGEN1884 in combination with AGEN2034 in
patients with advanced/refractory solid tumors, with expansion into select solid tumors.
METHODS• This is an ongoing phase 1/2, open-label, study of AGEN1884 in combination with AGEN2034 in subjects with
advanced solid tumors, including cervical cancer.
• The study consists of 2 phases: – Phase 1: Dose escalation (focus of this poster) – Phase 2: Expansion in select tumors (ongoing)
• Phase 1 consisted of a standard 3+3 dose escalation with the following escalating dose levels and schedules: – AGEN2034 1 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
– AGEN2034 3 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
• AGEN2034 was administered IV over 60 min and AGEN1884 IV over 90 mins. AGEN1884 was to be administered on the same day as AGEN2034 ≥30 min after the completion of AGEN2034 administration.
• Dose escalation will continue until AGEN2034 3 mg/kg + AGEN1884 1 mg/kg (maximum combination dose level) is shown to be safe or the maximum tolerated dose (de� ned as the combination below which ≥33% of subjects develop dose-limiting toxicities [DLTs]) is reached.
• A schematic of the phase 1 dose-escalation design is presented in Figure 2.
Figure 2. Dose-Escalation Study Flow
Starting dose
Treat 3 patients;Assess DLTs after 3 weeks
Number ofDLTs
No
Yes
≤1 of 6
0 of 3 ≥2 of 3
≥2 of 6
1 of 3
1 of 3
Treat additional 3 patients;Assess DLTs after 3 weeks
Number of DLTs
MTD/maximum CDL to be con�rmed on total
of 6 patients
Initiate phase 2 at maximum planned CDL
or MTD
Determine MTDEscalate to next CDL
Maximum CDL per protocol?
Determine MTD
CDL, combination dose level; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
• Each subject will receive the combination treatment for a maximum of 24 months or until con� rmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products occurs.
– Patients who do not complete the DLT observation period of 21 days after the � rst dose, for reasons other than a DLT, will be replaced.
– Cohorts will be back� lled to 10 subjects once they have reached DLT or MTD.
• Eligible patients include adults (aged ≥18 years) with a histologically or cytologically con� rmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• The treatment phase was divided into 6-week cycles, each beginning with the combined administration of AGEN2034 and AGEN1884 on day 1. Thereafter, AGEN2034 will be administrated q2w, completing the 6-week cycle.
– Tumor assessments are to be conducted at 6, 12, and 18 weeks from � rst dose, and every 9 weeks thereafter until disease progression is con� rmed or a new line of therapy is initiated.
• Phase 1 endpoints: – Primary: Occurrence of DLTs in patients in dose escalation during the � rst 21 days of treatment – Secondary:
Con� rmed best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as determined by the investigator
Frequency and nature of treatment-emergent adverse events (TEAEs) Pharmacokinetic pro� le and immunogenicity of AGEN1884 and AGEN2034
RESULTS • As of July 16, 2018, the study was ongoing, though total enrollment was achieved in the phase 1 portion
(ie, 10 patients in each dose cohort). Data are preliminary as it is being cleaned and/or collected at this time.
• Five patients had discontinued from the study treatment prior to data extract: – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=1; investigator decision, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=3
• There was 1 death not related to the study (66-year-old female with lung cancer treated with AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w died due to disease progression).
• Patients were Caucasian (100%) and primarily female (75%), with a median of 2.3 months from the most recent recurrence/progression to the administration of the � rst combination dose (Table 1).
• The cancer types for the 20 patients were as follows: breast cancer (triple negative, n=2; with lung metastases, n=1; with dermal lymphatics, n=1), ovarian cancer (n=2), mesothelioma (pleural, n=1; peritoneal, n=1), squamous carcinoma of head and neck (tongue; n=1), anal squamous carcinoma (n=1), pleomorphic soft tissue sarcoma (n=1), lung cancer (n=1), metastastic leiomyosarcoma (n=1), advanced gastrointestinal stromal tumor (n=1), rhabdomyosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), recurrent chordoma of the thoracic spine (n=1), chordoma (n=1), colorectal-rectal (n=1), esophageal adenocarcinoma (n=1).
Table 1. Demographics and Baseline Characteristics (Safety Set) AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Age (years)
Mean (SD) 58.4 (8.13) 47.6 (19.68) 53.0 (15.66)
Min, Max 43, 69 21, 79 21, 79
Female, n (%) 8 (80%) 7 (70%) 15 (75%)
BMI (kg/m2)
Mean (SD) 28.71 (8.227) 27.48 (7.006) 28.10 (7.464)
Min, Max 18.8, 40.9 20.9, 45.5 18.8, 45.5
ECOG performance status, n (%)
0 5 (50%) 7 (70%) 12 (60%)
1 5 (50%) 3 (30%) 8 (40%)
Time between most recent progression and � rst dose date (months)
n 6 6 12
Mean (SD) 2.26 (1.665) 2.34 (1.002) 2.30 (1.311)
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group.
• An overview of safety and tolerability is presented in Table 2.
Table 2. Overview of Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Any TEAE 10 (100%) 9 (90%) 19 (95%)
Any serious TEAE 3 (30%) 2 (20%) 5 (25%)
Any grade ≥3 TEAE 3 (30%) 2 (20%) 5 (25%)
Any immune-related TEAE 5 (50%) 4 (40%) 9 (45%)
Any treatment-related TEAE 8 (80%) 7 (70%) 15 (75%)
Any treatment-related serious TEAE 1 (10%) 2 (20%) 3 (15%)
Any treatment-related grade ≥3 TEAE 0 2 (20%) 2 (10%)
TEAE, treatment-emergent adverse event.
• As of July 16, 2018, no DLTs have been observed, and none of the TEAEs led to discontinuation or death.
• TEAEs were reported in 19 of 20 patients (95%), with the most common MedDRA version 18.1 preferred terms listed in (Table 3).
• Most TEAEs were mild to moderate in severity (grade 1 or 2); 5 patients experienced TEAEs of grade ≥3. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Vomiting, n=1; wound and cancer pain, n=1; hypotension, n=1
– AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection and pneumonia, n=1; pulmonary embolism, n=1
– Of these, the events of lower respiratory tract infection and pulmonary embolism were considered related to study treatment by the investigator.
Table 3. Most Common* Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Fatigue 5 (50%) 5 (50%) 10 (50%)
Nausea 3 (30%) 4 (40%) 7 (35%)
Pruritus 2 (20%) 3 (30%) 5 (25%)
Chills 3 (30%) 1 (10%) 4 (20%)
Vomiting 2 (20%) 2 (20%) 4 (20%)
Back pain 4 (40%) 0 4 (20%)*Occurring in ≥20% of patients.
• Serious TEAEs occurred in 5 patients: 3 receiving AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w and 2 receiving AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w
• 3 patients experienced serious TEAEs considered related to study treatment. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Diarrhea, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection, n=1; pulmonary embolism, n=1
• The summary of best overall response is listed in Table 4.
• The partial response was ongoing in one of the women with metastatic ovarian cancer. For patients with >90 days of treatment, stable disease was ongoing for 1 female with breast cancer (with lung metastases), 1 female with metastatic ovarian cancer, and 1 male with pleomorphic soft tissue sarcoma (with lung metastases).
Table 4. Summary of Best Overall Response at Time of Data Cut-off
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Complete response 0 0 0
Partial response 1 0 1
Stable disease 5 1 6
Progressive disease 3 6 9
Not evaluable 1 0 1
Pending 0 3 3Overall response determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
DISCUSSION• In the phase 1 portion, which is still ongoing, preliminary results demonstrate that AGEN1884 (1 mg/kg q6w) +
AGEN2034 (3 mg/kg q2w) is generally safe, well tolerated, and active in adults with select advanced/refractory solid tumors.
• The phase 2 portion of this study evaluating AGEN1884 in combination with AGEN2034 in adults with second-line cervical cancer and other solid tumors is ongoing.
– The phase 2 recommended dosing was determined as AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w.
References1. Topalian SL, Drake CG, Pardoll DM. Cancer Cell. 2015;27(4):450-61.2. Hodi FS, Chesney J, Pavlick AC, et al. Lancet Oncol.
2016;17(11):1558-68.
3. Antonia SJ, López-Martin JA, Bendell J, et al. Lancet Oncol. 2016;17(7):883-95.
4. Hellmann MD, Gettinger SN, Goldman JW, et al. J Clin Oncol. 2016;34(15 suppl):3001.5
Disclosures CD Dupont, AM Gonzalez, M Lim, D Savitsky, M Carini, S Hu, O Shebanova, E Dow, W Ortuzar, JS Buell, RB Stein, H Youssou� an: Agenus Inc.: current or former employment/consultancy and stock ownership.
Acknowledgments The authors thank Nicole Coolbaugh of The Medicine Group, LLC (New Hope, PA, USA) for providing medical writing and editorial support, which was funded by Agenus Inc. (Lexington, MA, USA) in accordance with Good Publication Practice guidelines. The licensed antibodies AGEN2034 and AGEN1884 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. Recepta Biopharma S.A. has exclusive rights to these antibodies in Brazil and � ve other South American countries.
Funding This study was funded by Agenus Inc. (Lexington, MA, USA).
CorrespondenceWaldo Ortuzar: [email protected]
Presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO), October 19–23, 2018, in Munich, Germany
Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors
Jermaine Coward,1 Charlotte Lemech,2 Tarek Meniawy,3 Christopher D. Dupont,4 Ana M. Gonzalez,4 Min Lim,4 David Savitsky,4 Meg Carini,4 Shuang Hu,4 Olga Shebanova,4 Ed Dow,4
Waldo Ortuzar,4 Jennifer S. Buell,4 Robert Benjamin Stein,4 Hagop Youssou� an4
1Icon Cancer Center, South Brisbane, Australia; 2Scientia Clinical Research, Sydney, Australia; 3Linear Clinical Research, Perth, Australia; 4Agenus Inc. or subsidiary thereof (current or former employee), Lexington, MA, USA
1168P
BACKGROUND• Antigen-speci� c T-cell activation is regulated by a balance of co-stimulatory and co-inhibitory signals, such as
those mediated by inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) (Figure 1).1
• Binding of these receptors to their ligands results in impaired T-cell function. For these reasons, antibody blockade of PD-1 and CTLA-4 has been identi� ed as a therapeutic modality to reinvigorate or induce tumor-speci� c T-cell immunity.1
Figure 1. Overview of Pathways Affected by CTLA-4 and PD-1CTLA-4 Inhibition PD-1 Inhibition
• In clinical trials, the combined inhibition of PD-1 and CTLA-4 pathways by blocking receptor-ligand interactions has resulted in objective clinical response and increased survival in several solid tumor indications, including melanoma and non-small cell lung carcinoma. As a result, ipilimumab (anti–CTLA-4) in combination with nivolumab (anti–PD-1) has been approved as a � rst line of treatment in patients with metastatic melanoma and is currently being tested in multiple other indications.2-4
• Agenus’ proprietary antibodies, AGEN2034 (anti–PD-1 human IgG4 monoclonal antibody) and AGEN1884 (anti–CTLA-4 human IgG1 monoclonal antibody) are currently under evaluation as monotherapy in phase 1/2 studies in subjects with advanced tumors (NCT03104699 and NCT02694822, respectively).
• A phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, and biological and clinical activity of AGEN1884 in combination with AGEN2034 in patients with metastatic or locally advanced solid tumors is currently ongoing (C550-01; ACTRN12618000003279; NCT03495882).
OBJECTIVE• The objective of this study is to assess safety and tolerability of AGEN1884 in combination with AGEN2034 in
patients with advanced/refractory solid tumors, with expansion into select solid tumors.
METHODS• This is an ongoing phase 1/2, open-label, study of AGEN1884 in combination with AGEN2034 in subjects with
advanced solid tumors, including cervical cancer.
• The study consists of 2 phases: – Phase 1: Dose escalation (focus of this poster) – Phase 2: Expansion in select tumors (ongoing)
• Phase 1 consisted of a standard 3+3 dose escalation with the following escalating dose levels and schedules: – AGEN2034 1 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
– AGEN2034 3 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
• AGEN2034 was administered IV over 60 min and AGEN1884 IV over 90 mins. AGEN1884 was to be administered on the same day as AGEN2034 ≥30 min after the completion of AGEN2034 administration.
• Dose escalation will continue until AGEN2034 3 mg/kg + AGEN1884 1 mg/kg (maximum combination dose level) is shown to be safe or the maximum tolerated dose (de� ned as the combination below which ≥33% of subjects develop dose-limiting toxicities [DLTs]) is reached.
• A schematic of the phase 1 dose-escalation design is presented in Figure 2.
Figure 2. Dose-Escalation Study Flow
Starting dose
Treat 3 patients;Assess DLTs after 3 weeks
Number ofDLTs
No
Yes
≤1 of 6
0 of 3 ≥2 of 3
≥2 of 6
1 of 3
1 of 3
Treat additional 3 patients;Assess DLTs after 3 weeks
Number of DLTs
MTD/maximum CDL to be con�rmed on total
of 6 patients
Initiate phase 2 at maximum planned CDL
or MTD
Determine MTDEscalate to next CDL
Maximum CDL per protocol?
Determine MTD
CDL, combination dose level; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
• Each subject will receive the combination treatment for a maximum of 24 months or until con� rmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products occurs.
– Patients who do not complete the DLT observation period of 21 days after the � rst dose, for reasons other than a DLT, will be replaced.
– Cohorts will be back� lled to 10 subjects once they have reached DLT or MTD.
• Eligible patients include adults (aged ≥18 years) with a histologically or cytologically con� rmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• The treatment phase was divided into 6-week cycles, each beginning with the combined administration of AGEN2034 and AGEN1884 on day 1. Thereafter, AGEN2034 will be administrated q2w, completing the 6-week cycle.
– Tumor assessments are to be conducted at 6, 12, and 18 weeks from � rst dose, and every 9 weeks thereafter until disease progression is con� rmed or a new line of therapy is initiated.
• Phase 1 endpoints: – Primary: Occurrence of DLTs in patients in dose escalation during the � rst 21 days of treatment – Secondary:
Con� rmed best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as determined by the investigator
Frequency and nature of treatment-emergent adverse events (TEAEs) Pharmacokinetic pro� le and immunogenicity of AGEN1884 and AGEN2034
RESULTS • As of July 16, 2018, the study was ongoing, though total enrollment was achieved in the phase 1 portion
(ie, 10 patients in each dose cohort). Data are preliminary as it is being cleaned and/or collected at this time.
• Five patients had discontinued from the study treatment prior to data extract: – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=1; investigator decision, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=3
• There was 1 death not related to the study (66-year-old female with lung cancer treated with AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w died due to disease progression).
• Patients were Caucasian (100%) and primarily female (75%), with a median of 2.3 months from the most recent recurrence/progression to the administration of the � rst combination dose (Table 1).
• The cancer types for the 20 patients were as follows: breast cancer (triple negative, n=2; with lung metastases, n=1; with dermal lymphatics, n=1), ovarian cancer (n=2), mesothelioma (pleural, n=1; peritoneal, n=1), squamous carcinoma of head and neck (tongue; n=1), anal squamous carcinoma (n=1), pleomorphic soft tissue sarcoma (n=1), lung cancer (n=1), metastastic leiomyosarcoma (n=1), advanced gastrointestinal stromal tumor (n=1), rhabdomyosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), recurrent chordoma of the thoracic spine (n=1), chordoma (n=1), colorectal-rectal (n=1), esophageal adenocarcinoma (n=1).
Table 1. Demographics and Baseline Characteristics (Safety Set) AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Age (years)
Mean (SD) 58.4 (8.13) 47.6 (19.68) 53.0 (15.66)
Min, Max 43, 69 21, 79 21, 79
Female, n (%) 8 (80%) 7 (70%) 15 (75%)
BMI (kg/m2)
Mean (SD) 28.71 (8.227) 27.48 (7.006) 28.10 (7.464)
Min, Max 18.8, 40.9 20.9, 45.5 18.8, 45.5
ECOG performance status, n (%)
0 5 (50%) 7 (70%) 12 (60%)
1 5 (50%) 3 (30%) 8 (40%)
Time between most recent progression and � rst dose date (months)
n 6 6 12
Mean (SD) 2.26 (1.665) 2.34 (1.002) 2.30 (1.311)
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group.
• An overview of safety and tolerability is presented in Table 2.
Table 2. Overview of Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Any TEAE 10 (100%) 9 (90%) 19 (95%)
Any serious TEAE 3 (30%) 2 (20%) 5 (25%)
Any grade ≥3 TEAE 3 (30%) 2 (20%) 5 (25%)
Any immune-related TEAE 5 (50%) 4 (40%) 9 (45%)
Any treatment-related TEAE 8 (80%) 7 (70%) 15 (75%)
Any treatment-related serious TEAE 1 (10%) 2 (20%) 3 (15%)
Any treatment-related grade ≥3 TEAE 0 2 (20%) 2 (10%)
TEAE, treatment-emergent adverse event.
• As of July 16, 2018, no DLTs have been observed, and none of the TEAEs led to discontinuation or death.
• TEAEs were reported in 19 of 20 patients (95%), with the most common MedDRA version 18.1 preferred terms listed in (Table 3).
• Most TEAEs were mild to moderate in severity (grade 1 or 2); 5 patients experienced TEAEs of grade ≥3. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Vomiting, n=1; wound and cancer pain, n=1; hypotension, n=1
– AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection and pneumonia, n=1; pulmonary embolism, n=1
– Of these, the events of lower respiratory tract infection and pulmonary embolism were considered related to study treatment by the investigator.
Table 3. Most Common* Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Fatigue 5 (50%) 5 (50%) 10 (50%)
Nausea 3 (30%) 4 (40%) 7 (35%)
Pruritus 2 (20%) 3 (30%) 5 (25%)
Chills 3 (30%) 1 (10%) 4 (20%)
Vomiting 2 (20%) 2 (20%) 4 (20%)
Back pain 4 (40%) 0 4 (20%)*Occurring in ≥20% of patients.
• Serious TEAEs occurred in 5 patients: 3 receiving AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w and 2 receiving AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w
• 3 patients experienced serious TEAEs considered related to study treatment. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Diarrhea, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection, n=1; pulmonary embolism, n=1
• The summary of best overall response is listed in Table 4.
• The partial response was ongoing in one of the women with metastatic ovarian cancer. For patients with >90 days of treatment, stable disease was ongoing for 1 female with breast cancer (with lung metastases), 1 female with metastatic ovarian cancer, and 1 male with pleomorphic soft tissue sarcoma (with lung metastases).
Table 4. Summary of Best Overall Response at Time of Data Cut-off
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Complete response 0 0 0
Partial response 1 0 1
Stable disease 5 1 6
Progressive disease 3 6 9
Not evaluable 1 0 1
Pending 0 3 3Overall response determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
DISCUSSION• In the phase 1 portion, which is still ongoing, preliminary results demonstrate that AGEN1884 (1 mg/kg q6w) +
AGEN2034 (3 mg/kg q2w) is generally safe, well tolerated, and active in adults with select advanced/refractory solid tumors.
• The phase 2 portion of this study evaluating AGEN1884 in combination with AGEN2034 in adults with second-line cervical cancer and other solid tumors is ongoing.
– The phase 2 recommended dosing was determined as AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w.
References1. Topalian SL, Drake CG, Pardoll DM. Cancer Cell. 2015;27(4):450-61.2. Hodi FS, Chesney J, Pavlick AC, et al. Lancet Oncol.
2016;17(11):1558-68.
3. Antonia SJ, López-Martin JA, Bendell J, et al. Lancet Oncol. 2016;17(7):883-95.
4. Hellmann MD, Gettinger SN, Goldman JW, et al. J Clin Oncol. 2016;34(15 suppl):3001.5
Disclosures CD Dupont, AM Gonzalez, M Lim, D Savitsky, M Carini, S Hu, O Shebanova, E Dow, W Ortuzar, JS Buell, RB Stein, H Youssou� an: Agenus Inc.: current or former employment/consultancy and stock ownership.
Acknowledgments The authors thank Nicole Coolbaugh of The Medicine Group, LLC (New Hope, PA, USA) for providing medical writing and editorial support, which was funded by Agenus Inc. (Lexington, MA, USA) in accordance with Good Publication Practice guidelines. The licensed antibodies AGEN2034 and AGEN1884 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. Recepta Biopharma S.A. has exclusive rights to these antibodies in Brazil and � ve other South American countries.
Funding This study was funded by Agenus Inc. (Lexington, MA, USA).
CorrespondenceWaldo Ortuzar: [email protected]
Presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO), October 19–23, 2018, in Munich, Germany
Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors
Jermaine Coward,1 Charlotte Lemech,2 Tarek Meniawy,3 Christopher D. Dupont,4 Ana M. Gonzalez,4 Min Lim,4 David Savitsky,4 Meg Carini,4 Shuang Hu,4 Olga Shebanova,4 Ed Dow,4
Waldo Ortuzar,4 Jennifer S. Buell,4 Robert Benjamin Stein,4 Hagop Youssou� an4
1Icon Cancer Center, South Brisbane, Australia; 2Scientia Clinical Research, Sydney, Australia; 3Linear Clinical Research, Perth, Australia; 4Agenus Inc. or subsidiary thereof (current or former employee), Lexington, MA, USA
1168P
BACKGROUND• Antigen-speci� c T-cell activation is regulated by a balance of co-stimulatory and co-inhibitory signals, such as
those mediated by inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) (Figure 1).1
• Binding of these receptors to their ligands results in impaired T-cell function. For these reasons, antibody blockade of PD-1 and CTLA-4 has been identi� ed as a therapeutic modality to reinvigorate or induce tumor-speci� c T-cell immunity.1
Figure 1. Overview of Pathways Affected by CTLA-4 and PD-1CTLA-4 Inhibition PD-1 Inhibition
• In clinical trials, the combined inhibition of PD-1 and CTLA-4 pathways by blocking receptor-ligand interactions has resulted in objective clinical response and increased survival in several solid tumor indications, including melanoma and non-small cell lung carcinoma. As a result, ipilimumab (anti–CTLA-4) in combination with nivolumab (anti–PD-1) has been approved as a � rst line of treatment in patients with metastatic melanoma and is currently being tested in multiple other indications.2-4
• Agenus’ proprietary antibodies, AGEN2034 (anti–PD-1 human IgG4 monoclonal antibody) and AGEN1884 (anti–CTLA-4 human IgG1 monoclonal antibody) are currently under evaluation as monotherapy in phase 1/2 studies in subjects with advanced tumors (NCT03104699 and NCT02694822, respectively).
• A phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, and biological and clinical activity of AGEN1884 in combination with AGEN2034 in patients with metastatic or locally advanced solid tumors is currently ongoing (C550-01; ACTRN12618000003279; NCT03495882).
OBJECTIVE• The objective of this study is to assess safety and tolerability of AGEN1884 in combination with AGEN2034 in
patients with advanced/refractory solid tumors, with expansion into select solid tumors.
METHODS• This is an ongoing phase 1/2, open-label, study of AGEN1884 in combination with AGEN2034 in subjects with
advanced solid tumors, including cervical cancer.
• The study consists of 2 phases: – Phase 1: Dose escalation (focus of this poster) – Phase 2: Expansion in select tumors (ongoing)
• Phase 1 consisted of a standard 3+3 dose escalation with the following escalating dose levels and schedules: – AGEN2034 1 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
– AGEN2034 3 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
• AGEN2034 was administered IV over 60 min and AGEN1884 IV over 90 mins. AGEN1884 was to be administered on the same day as AGEN2034 ≥30 min after the completion of AGEN2034 administration.
• Dose escalation will continue until AGEN2034 3 mg/kg + AGEN1884 1 mg/kg (maximum combination dose level) is shown to be safe or the maximum tolerated dose (de� ned as the combination below which ≥33% of subjects develop dose-limiting toxicities [DLTs]) is reached.
• A schematic of the phase 1 dose-escalation design is presented in Figure 2.
Figure 2. Dose-Escalation Study Flow
Starting dose
Treat 3 patients;Assess DLTs after 3 weeks
Number ofDLTs
No
Yes
≤1 of 6
0 of 3 ≥2 of 3
≥2 of 6
1 of 3
1 of 3
Treat additional 3 patients;Assess DLTs after 3 weeks
Number of DLTs
MTD/maximum CDL to be con�rmed on total
of 6 patients
Initiate phase 2 at maximum planned CDL
or MTD
Determine MTDEscalate to next CDL
Maximum CDL per protocol?
Determine MTD
CDL, combination dose level; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
• Each subject will receive the combination treatment for a maximum of 24 months or until con� rmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products occurs.
– Patients who do not complete the DLT observation period of 21 days after the � rst dose, for reasons other than a DLT, will be replaced.
– Cohorts will be back� lled to 10 subjects once they have reached DLT or MTD.
• Eligible patients include adults (aged ≥18 years) with a histologically or cytologically con� rmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• The treatment phase was divided into 6-week cycles, each beginning with the combined administration of AGEN2034 and AGEN1884 on day 1. Thereafter, AGEN2034 will be administrated q2w, completing the 6-week cycle.
– Tumor assessments are to be conducted at 6, 12, and 18 weeks from � rst dose, and every 9 weeks thereafter until disease progression is con� rmed or a new line of therapy is initiated.
• Phase 1 endpoints: – Primary: Occurrence of DLTs in patients in dose escalation during the � rst 21 days of treatment – Secondary:
Con� rmed best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as determined by the investigator
Frequency and nature of treatment-emergent adverse events (TEAEs) Pharmacokinetic pro� le and immunogenicity of AGEN1884 and AGEN2034
RESULTS • As of July 16, 2018, the study was ongoing, though total enrollment was achieved in the phase 1 portion
(ie, 10 patients in each dose cohort). Data are preliminary as it is being cleaned and/or collected at this time.
• Five patients had discontinued from the study treatment prior to data extract: – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=1; investigator decision, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=3
• There was 1 death not related to the study (66-year-old female with lung cancer treated with AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w died due to disease progression).
• Patients were Caucasian (100%) and primarily female (75%), with a median of 2.3 months from the most recent recurrence/progression to the administration of the � rst combination dose (Table 1).
• The cancer types for the 20 patients were as follows: breast cancer (triple negative, n=2; with lung metastases, n=1; with dermal lymphatics, n=1), ovarian cancer (n=2), mesothelioma (pleural, n=1; peritoneal, n=1), squamous carcinoma of head and neck (tongue; n=1), anal squamous carcinoma (n=1), pleomorphic soft tissue sarcoma (n=1), lung cancer (n=1), metastastic leiomyosarcoma (n=1), advanced gastrointestinal stromal tumor (n=1), rhabdomyosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), recurrent chordoma of the thoracic spine (n=1), chordoma (n=1), colorectal-rectal (n=1), esophageal adenocarcinoma (n=1).
Table 1. Demographics and Baseline Characteristics (Safety Set) AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Age (years)
Mean (SD) 58.4 (8.13) 47.6 (19.68) 53.0 (15.66)
Min, Max 43, 69 21, 79 21, 79
Female, n (%) 8 (80%) 7 (70%) 15 (75%)
BMI (kg/m2)
Mean (SD) 28.71 (8.227) 27.48 (7.006) 28.10 (7.464)
Min, Max 18.8, 40.9 20.9, 45.5 18.8, 45.5
ECOG performance status, n (%)
0 5 (50%) 7 (70%) 12 (60%)
1 5 (50%) 3 (30%) 8 (40%)
Time between most recent progression and � rst dose date (months)
n 6 6 12
Mean (SD) 2.26 (1.665) 2.34 (1.002) 2.30 (1.311)
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group.
• An overview of safety and tolerability is presented in Table 2.
Table 2. Overview of Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Any TEAE 10 (100%) 9 (90%) 19 (95%)
Any serious TEAE 3 (30%) 2 (20%) 5 (25%)
Any grade ≥3 TEAE 3 (30%) 2 (20%) 5 (25%)
Any immune-related TEAE 5 (50%) 4 (40%) 9 (45%)
Any treatment-related TEAE 8 (80%) 7 (70%) 15 (75%)
Any treatment-related serious TEAE 1 (10%) 2 (20%) 3 (15%)
Any treatment-related grade ≥3 TEAE 0 2 (20%) 2 (10%)
TEAE, treatment-emergent adverse event.
• As of July 16, 2018, no DLTs have been observed, and none of the TEAEs led to discontinuation or death.
• TEAEs were reported in 19 of 20 patients (95%), with the most common MedDRA version 18.1 preferred terms listed in (Table 3).
• Most TEAEs were mild to moderate in severity (grade 1 or 2); 5 patients experienced TEAEs of grade ≥3. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Vomiting, n=1; wound and cancer pain, n=1; hypotension, n=1
– AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection and pneumonia, n=1; pulmonary embolism, n=1
– Of these, the events of lower respiratory tract infection and pulmonary embolism were considered related to study treatment by the investigator.
Table 3. Most Common* Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Fatigue 5 (50%) 5 (50%) 10 (50%)
Nausea 3 (30%) 4 (40%) 7 (35%)
Pruritus 2 (20%) 3 (30%) 5 (25%)
Chills 3 (30%) 1 (10%) 4 (20%)
Vomiting 2 (20%) 2 (20%) 4 (20%)
Back pain 4 (40%) 0 4 (20%)*Occurring in ≥20% of patients.
• Serious TEAEs occurred in 5 patients: 3 receiving AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w and 2 receiving AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w
• 3 patients experienced serious TEAEs considered related to study treatment. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Diarrhea, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection, n=1; pulmonary embolism, n=1
• The summary of best overall response is listed in Table 4.
• The partial response was ongoing in one of the women with metastatic ovarian cancer. For patients with >90 days of treatment, stable disease was ongoing for 1 female with breast cancer (with lung metastases), 1 female with metastatic ovarian cancer, and 1 male with pleomorphic soft tissue sarcoma (with lung metastases).
Table 4. Summary of Best Overall Response at Time of Data Cut-off
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Complete response 0 0 0
Partial response 1 0 1
Stable disease 5 1 6
Progressive disease 3 6 9
Not evaluable 1 0 1
Pending 0 3 3Overall response determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
DISCUSSION• In the phase 1 portion, which is still ongoing, preliminary results demonstrate that AGEN1884 (1 mg/kg q6w) +
AGEN2034 (3 mg/kg q2w) is generally safe, well tolerated, and active in adults with select advanced/refractory solid tumors.
• The phase 2 portion of this study evaluating AGEN1884 in combination with AGEN2034 in adults with second-line cervical cancer and other solid tumors is ongoing.
– The phase 2 recommended dosing was determined as AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w.
References1. Topalian SL, Drake CG, Pardoll DM. Cancer Cell. 2015;27(4):450-61.2. Hodi FS, Chesney J, Pavlick AC, et al. Lancet Oncol.
2016;17(11):1558-68.
3. Antonia SJ, López-Martin JA, Bendell J, et al. Lancet Oncol. 2016;17(7):883-95.
4. Hellmann MD, Gettinger SN, Goldman JW, et al. J Clin Oncol. 2016;34(15 suppl):3001.5
Disclosures CD Dupont, AM Gonzalez, M Lim, D Savitsky, M Carini, S Hu, O Shebanova, E Dow, W Ortuzar, JS Buell, RB Stein, H Youssou� an: Agenus Inc.: current or former employment/consultancy and stock ownership.
Acknowledgments The authors thank Nicole Coolbaugh of The Medicine Group, LLC (New Hope, PA, USA) for providing medical writing and editorial support, which was funded by Agenus Inc. (Lexington, MA, USA) in accordance with Good Publication Practice guidelines. The licensed antibodies AGEN2034 and AGEN1884 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. Recepta Biopharma S.A. has exclusive rights to these antibodies in Brazil and � ve other South American countries.
Funding This study was funded by Agenus Inc. (Lexington, MA, USA).
CorrespondenceWaldo Ortuzar: [email protected]
Presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO), October 19–23, 2018, in Munich, Germany
Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors
Jermaine Coward,1 Charlotte Lemech,2 Tarek Meniawy,3 Christopher D. Dupont,4 Ana M. Gonzalez,4 Min Lim,4 David Savitsky,4 Meg Carini,4 Shuang Hu,4 Olga Shebanova,4 Ed Dow,4
Waldo Ortuzar,4 Jennifer S. Buell,4 Robert Benjamin Stein,4 Hagop Youssou� an4
1Icon Cancer Center, South Brisbane, Australia; 2Scientia Clinical Research, Sydney, Australia; 3Linear Clinical Research, Perth, Australia; 4Agenus Inc. or subsidiary thereof (current or former employee), Lexington, MA, USA
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BACKGROUND• Antigen-speci� c T-cell activation is regulated by a balance of co-stimulatory and co-inhibitory signals, such as
those mediated by inhibitory receptors cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) (Figure 1).1
• Binding of these receptors to their ligands results in impaired T-cell function. For these reasons, antibody blockade of PD-1 and CTLA-4 has been identi� ed as a therapeutic modality to reinvigorate or induce tumor-speci� c T-cell immunity.1
Figure 1. Overview of Pathways Affected by CTLA-4 and PD-1CTLA-4 Inhibition PD-1 Inhibition
• In clinical trials, the combined inhibition of PD-1 and CTLA-4 pathways by blocking receptor-ligand interactions has resulted in objective clinical response and increased survival in several solid tumor indications, including melanoma and non-small cell lung carcinoma. As a result, ipilimumab (anti–CTLA-4) in combination with nivolumab (anti–PD-1) has been approved as a � rst line of treatment in patients with metastatic melanoma and is currently being tested in multiple other indications.2-4
• Agenus’ proprietary antibodies, AGEN2034 (anti–PD-1 human IgG4 monoclonal antibody) and AGEN1884 (anti–CTLA-4 human IgG1 monoclonal antibody) are currently under evaluation as monotherapy in phase 1/2 studies in subjects with advanced tumors (NCT03104699 and NCT02694822, respectively).
• A phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, and biological and clinical activity of AGEN1884 in combination with AGEN2034 in patients with metastatic or locally advanced solid tumors is currently ongoing (C550-01; ACTRN12618000003279; NCT03495882).
OBJECTIVE• The objective of this study is to assess safety and tolerability of AGEN1884 in combination with AGEN2034 in
patients with advanced/refractory solid tumors, with expansion into select solid tumors.
METHODS• This is an ongoing phase 1/2, open-label, study of AGEN1884 in combination with AGEN2034 in subjects with
advanced solid tumors, including cervical cancer.
• The study consists of 2 phases: – Phase 1: Dose escalation (focus of this poster) – Phase 2: Expansion in select tumors (ongoing)
• Phase 1 consisted of a standard 3+3 dose escalation with the following escalating dose levels and schedules: – AGEN2034 1 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
– AGEN2034 3 mg/kg administered every 2 weeks (q2w) in combination with AGEN1884 1 mg/kg administered every 6 weeks (q6w)
• AGEN2034 was administered IV over 60 min and AGEN1884 IV over 90 mins. AGEN1884 was to be administered on the same day as AGEN2034 ≥30 min after the completion of AGEN2034 administration.
• Dose escalation will continue until AGEN2034 3 mg/kg + AGEN1884 1 mg/kg (maximum combination dose level) is shown to be safe or the maximum tolerated dose (de� ned as the combination below which ≥33% of subjects develop dose-limiting toxicities [DLTs]) is reached.
• A schematic of the phase 1 dose-escalation design is presented in Figure 2.
Figure 2. Dose-Escalation Study Flow
Starting dose
Treat 3 patients;Assess DLTs after 3 weeks
Number ofDLTs
No
Yes
≤1 of 6
0 of 3 ≥2 of 3
≥2 of 6
1 of 3
1 of 3
Treat additional 3 patients;Assess DLTs after 3 weeks
Number of DLTs
MTD/maximum CDL to be con�rmed on total
of 6 patients
Initiate phase 2 at maximum planned CDL
or MTD
Determine MTDEscalate to next CDL
Maximum CDL per protocol?
Determine MTD
CDL, combination dose level; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
• Each subject will receive the combination treatment for a maximum of 24 months or until con� rmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the trial or the investigational medicinal products occurs.
– Patients who do not complete the DLT observation period of 21 days after the � rst dose, for reasons other than a DLT, will be replaced.
– Cohorts will be back� lled to 10 subjects once they have reached DLT or MTD.
• Eligible patients include adults (aged ≥18 years) with a histologically or cytologically con� rmed diagnosis of a metastatic or locally advanced solid tumor for which no standard therapy is available or standard therapy has failed.
• The treatment phase was divided into 6-week cycles, each beginning with the combined administration of AGEN2034 and AGEN1884 on day 1. Thereafter, AGEN2034 will be administrated q2w, completing the 6-week cycle.
– Tumor assessments are to be conducted at 6, 12, and 18 weeks from � rst dose, and every 9 weeks thereafter until disease progression is con� rmed or a new line of therapy is initiated.
• Phase 1 endpoints: – Primary: Occurrence of DLTs in patients in dose escalation during the � rst 21 days of treatment – Secondary:
Con� rmed best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as determined by the investigator
Frequency and nature of treatment-emergent adverse events (TEAEs) Pharmacokinetic pro� le and immunogenicity of AGEN1884 and AGEN2034
RESULTS • As of July 16, 2018, the study was ongoing, though total enrollment was achieved in the phase 1 portion
(ie, 10 patients in each dose cohort). Data are preliminary as it is being cleaned and/or collected at this time.
• Five patients had discontinued from the study treatment prior to data extract: – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=1; investigator decision, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Progressive disease, n=3
• There was 1 death not related to the study (66-year-old female with lung cancer treated with AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w died due to disease progression).
• Patients were Caucasian (100%) and primarily female (75%), with a median of 2.3 months from the most recent recurrence/progression to the administration of the � rst combination dose (Table 1).
• The cancer types for the 20 patients were as follows: breast cancer (triple negative, n=2; with lung metastases, n=1; with dermal lymphatics, n=1), ovarian cancer (n=2), mesothelioma (pleural, n=1; peritoneal, n=1), squamous carcinoma of head and neck (tongue; n=1), anal squamous carcinoma (n=1), pleomorphic soft tissue sarcoma (n=1), lung cancer (n=1), metastastic leiomyosarcoma (n=1), advanced gastrointestinal stromal tumor (n=1), rhabdomyosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), recurrent chordoma of the thoracic spine (n=1), chordoma (n=1), colorectal-rectal (n=1), esophageal adenocarcinoma (n=1).
Table 1. Demographics and Baseline Characteristics (Safety Set) AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Age (years)
Mean (SD) 58.4 (8.13) 47.6 (19.68) 53.0 (15.66)
Min, Max 43, 69 21, 79 21, 79
Female, n (%) 8 (80%) 7 (70%) 15 (75%)
BMI (kg/m2)
Mean (SD) 28.71 (8.227) 27.48 (7.006) 28.10 (7.464)
Min, Max 18.8, 40.9 20.9, 45.5 18.8, 45.5
ECOG performance status, n (%)
0 5 (50%) 7 (70%) 12 (60%)
1 5 (50%) 3 (30%) 8 (40%)
Time between most recent progression and � rst dose date (months)
n 6 6 12
Mean (SD) 2.26 (1.665) 2.34 (1.002) 2.30 (1.311)
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group.
• An overview of safety and tolerability is presented in Table 2.
Table 2. Overview of Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Any TEAE 10 (100%) 9 (90%) 19 (95%)
Any serious TEAE 3 (30%) 2 (20%) 5 (25%)
Any grade ≥3 TEAE 3 (30%) 2 (20%) 5 (25%)
Any immune-related TEAE 5 (50%) 4 (40%) 9 (45%)
Any treatment-related TEAE 8 (80%) 7 (70%) 15 (75%)
Any treatment-related serious TEAE 1 (10%) 2 (20%) 3 (15%)
Any treatment-related grade ≥3 TEAE 0 2 (20%) 2 (10%)
TEAE, treatment-emergent adverse event.
• As of July 16, 2018, no DLTs have been observed, and none of the TEAEs led to discontinuation or death.
• TEAEs were reported in 19 of 20 patients (95%), with the most common MedDRA version 18.1 preferred terms listed in (Table 3).
• Most TEAEs were mild to moderate in severity (grade 1 or 2); 5 patients experienced TEAEs of grade ≥3. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Vomiting, n=1; wound and cancer pain, n=1; hypotension, n=1
– AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection and pneumonia, n=1; pulmonary embolism, n=1
– Of these, the events of lower respiratory tract infection and pulmonary embolism were considered related to study treatment by the investigator.
Table 3. Most Common* Treatment-Emergent Adverse Event (Safety Set)
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Fatigue 5 (50%) 5 (50%) 10 (50%)
Nausea 3 (30%) 4 (40%) 7 (35%)
Pruritus 2 (20%) 3 (30%) 5 (25%)
Chills 3 (30%) 1 (10%) 4 (20%)
Vomiting 2 (20%) 2 (20%) 4 (20%)
Back pain 4 (40%) 0 4 (20%)*Occurring in ≥20% of patients.
• Serious TEAEs occurred in 5 patients: 3 receiving AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w and 2 receiving AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w
• 3 patients experienced serious TEAEs considered related to study treatment. – AGEN2034 1 mg/kg q2w + AGEN1884 1 mg/kg q6w: Diarrhea, n=1 – AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w: Lower respiratory tract infection, n=1; pulmonary embolism, n=1
• The summary of best overall response is listed in Table 4.
• The partial response was ongoing in one of the women with metastatic ovarian cancer. For patients with >90 days of treatment, stable disease was ongoing for 1 female with breast cancer (with lung metastases), 1 female with metastatic ovarian cancer, and 1 male with pleomorphic soft tissue sarcoma (with lung metastases).
Table 4. Summary of Best Overall Response at Time of Data Cut-off
Patients, n (%)
AGEN2034 1 mg/kg + AGEN1884 1 mg/kg
(N=10)
AGEN2034 3 mg/kg + AGEN1884 1 mg/kg
(N=10)Total Patients
(N=20)
Complete response 0 0 0
Partial response 1 0 1
Stable disease 5 1 6
Progressive disease 3 6 9
Not evaluable 1 0 1
Pending 0 3 3Overall response determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
DISCUSSION• In the phase 1 portion, which is still ongoing, preliminary results demonstrate that AGEN1884 (1 mg/kg q6w) +
AGEN2034 (3 mg/kg q2w) is generally safe, well tolerated, and active in adults with select advanced/refractory solid tumors.
• The phase 2 portion of this study evaluating AGEN1884 in combination with AGEN2034 in adults with second-line cervical cancer and other solid tumors is ongoing.
– The phase 2 recommended dosing was determined as AGEN2034 3 mg/kg q2w + AGEN1884 1 mg/kg q6w.
References1. Topalian SL, Drake CG, Pardoll DM. Cancer Cell. 2015;27(4):450-61.2. Hodi FS, Chesney J, Pavlick AC, et al. Lancet Oncol.
2016;17(11):1558-68.
3. Antonia SJ, López-Martin JA, Bendell J, et al. Lancet Oncol. 2016;17(7):883-95.
4. Hellmann MD, Gettinger SN, Goldman JW, et al. J Clin Oncol. 2016;34(15 suppl):3001.5
Disclosures CD Dupont, AM Gonzalez, M Lim, D Savitsky, M Carini, S Hu, O Shebanova, E Dow, W Ortuzar, JS Buell, RB Stein, H Youssou� an: Agenus Inc.: current or former employment/consultancy and stock ownership.
Acknowledgments The authors thank Nicole Coolbaugh of The Medicine Group, LLC (New Hope, PA, USA) for providing medical writing and editorial support, which was funded by Agenus Inc. (Lexington, MA, USA) in accordance with Good Publication Practice guidelines. The licensed antibodies AGEN2034 and AGEN1884 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. Recepta Biopharma S.A. has exclusive rights to these antibodies in Brazil and � ve other South American countries.
Funding This study was funded by Agenus Inc. (Lexington, MA, USA).
CorrespondenceWaldo Ortuzar: [email protected]
Presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO), October 19–23, 2018, in Munich, Germany
Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors
Jermaine Coward,1 Charlotte Lemech,2 Tarek Meniawy,3 Christopher D. Dupont,4 Ana M. Gonzalez,4 Min Lim,4 David Savitsky,4 Meg Carini,4 Shuang Hu,4 Olga Shebanova,4 Ed Dow,4
Waldo Ortuzar,4 Jennifer S. Buell,4 Robert Benjamin Stein,4 Hagop Youssou� an4
1Icon Cancer Center, South Brisbane, Australia; 2Scientia Clinical Research, Sydney, Australia; 3Linear Clinical Research, Perth, Australia; 4Agenus Inc. or subsidiary thereof (current or former employee), Lexington, MA, USA
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