th world congress on gastrointestinal cancer, barcelona … · 2018. 7. 9. · safety of...
TRANSCRIPT
June 22nd, 2018Highlights of Posters on Colorectal Cancer (CRC)
Takayuki YOSHINO, M.D.Director, Department of Gastroenterology and Gastrointestinal Oncology,National Cancer Center Hospital East (NCCE), Japan
ESMO 20th World Congress on Gastrointestinal Cancer, Barcelona
Highlights No-lights as well!
Disclosure of Conflict of Interests
Research Funding: Chugai, MSD, Sanofi, Sumitomo Dainippon,
GlaxoSmithKline and Boehringer Ingelheim
Lecture Fee:Sanofi, Chugai, Eli Lilly, and Merck Serono
Colorectal Cancer (CRC) Track
• Selected Abstract (Oral): 23• Poster Discussion (PD): 15• Poster (P): 136
Presentations on ESMO-GI 2018
I would like to Highlight ONLY
PD & P!
Posters are presented today, and there are only few hours left for preparing for my presentation slide deck!!!
However, NO enough time for preparation…
Oh My God!
# Brief Title Author
PD-006 DNA CNV for CRLM M Marques
PD-007 Network analysis S Choi
PD-008 Molecular character of immune M Giordano
PD-009 Acquired resistance for EGFR blockade T Yamada
PD-010 REVERCE QoL T Yoshino
PD-011 SAPHIRE M Takahashi
PD-012 ETS and tr-Symtoms: 3 Pani studies J Taieb
PD-013 Usefulness of ICG J Park
PD-014 Brain meta: Danish population-bd A Boysen
PD-015 1L in mCRC with mucinous V Catalano
PD-016 Safety of SEMS(Stents) for GiP V P-Barcia
PD-017 Extrahepatic PD in CRLM E Ongaro
PD-018 Left vs. Right: Belgium population-bd K Janssens
PD-019 RENCA Macrobead therapy A Nazarian
PD-020 XELAVIRI RAS status and Age D Modest
Poster Discussions
“Highlights”Posters
Selection from 15 Poster Discussions
# Brief Title Author
PD-006 DNA CNV for CRLM M Marques
PD-007 Network analysis S Choi
PD-008 Molecular character of immune M Giordano
PD-009 Acquired resistance for EGFR blockade T Yamada
PD-010 REVERCE QoL T Yoshino
PD-011 SAPHIRE M Takahashi
PD-012 ETS and tr-Symtoms: 3 Pani studies J Taieb
PD-013 Usefulness of ICG J Park
PD-014 Brain meta: Danish population-bd A Boysen
PD-015 1L in mCRC with mucinous V Catalano
PD-016 Safety of SEMS(Stents) for GiP V P-Barcia
PD-017 Extrahepatic PD in CRLM E Ongaro
PD-018 Left vs. Right: Belgium population-bd K Janssens
PD-019 RENCA Macrobead therapy A Nazarian
PD-020 XELAVIRI RAS status and Age D Modest
Poster Discussions
“Highlights”Posters
Focusing on4 chemo abstracts
Selection from 15 Poster Discussions
QOL evaluation by EQ-5D
PD or
unacceptable
toxicities
1:1
• Metastatic CRC• Treatment failure with
FP, oxaliplatin, and irinotecan
• Anti-EGFR naive• KRAS exon 2 WT• Pts. with minor RAS
mutations are excluded since March 2015
Treatment 1 (Tx1) Treatment 2 (Tx2)R-C arm
C-R arm
Regorafenib 160 mg
Cetuximab(+ irinotecan)
Cetuximab(+ irinotecan)
Regorafenib160 mg
Primary endpoint: OSSecondary endpoint: TTF, PFS, ORR, DCR, toxicities, and QOL by EQ-5D (pre, at week 4, and 8 in Tx1 and 2) 0.00
0.25
0.50
0.75
1.00
Prop
ortio
n
0 6 12 18 24 30 36 42Time (months)
HR* = 0.61 (95%CI: 0.39-0.96)Stratified log rank p = 0.029
*adjusted by intent to use irinotecanMedian follow-up: 29.0 months
Event/N % Median (months)
R-C 37/51 73% 17.4 (10.5-20.7)
C-R 44/50 88% 11.6 (8.4-12.9)
QoL score by EQ5D
BeforeTx1
Tx14 weeks
Tx18 weeks
BeforeTx2
Tx24 weeks
Tx28 weeks
0.500.55
0.60
0.650.70
0.75
0.800.85
0.900.95
1.00
Mea
n EQ
-5D
inde
x
C-RR-C
Error bars represent 95% CI
Regorafenib
Cetuximab Cetuximab
Regorafenib
#PD-010 REVERCE QoLOS
-0.20 -0.15 -0.10 -0.05 0.00 0.05 0.10Estimate
Anorexia
Fatigue
HFSR
Rash
Adverse event
G1 vs G0G2 vs G0G1 vs G0G2 vs G0G1 vs G0G2 vs G0G1 vs G0G2 vs G0
Grade
0.001 (-0.052, 0.055)-0.061 (-0.121, -0.002)-0.030 (-0.067, 0.006)-0.106 (-0.173, -0.039)-0.004 (-0.040, 0.032)-0.025 (-0.071, 0.022)0.008 (-0.031, 0.047)0.011 (-0.043, 0.065)
Estimate (95% CI)
0.9580.0430.1060.0020.8320.3000.6860.695
P
N=180
PD or
unacceptable
toxicities
3 wks on, 1 wk off
3 wks on, 1 wk off
T Yoshino et al. ESMO-GI 2018 #PD-010.
QOL evaluation by EQ-5D
PD or
unacceptable
toxicities
1:1
• Metastatic CRC• Treatment failure with
FP, oxaliplatin, and irinotecan
• Anti-EGFR naive• KRAS exon 2 WT• Pts. with minor RAS
mutations are excluded since March 2015
Treatment 1 (Tx1) Treatment 2 (Tx2)R-C arm
C-R arm
Regorafenib 160 mg
Cetuximab(+ irinotecan)
Cetuximab(+ irinotecan)
Regorafenib160 mg
Primary endpoint: OSSecondary endpoint: TTF, PFS, ORR, DCR, toxicities, and QOL by EQ-5D (pre, at week 4, and 8 in Tx1 and 2) 0.00
0.25
0.50
0.75
1.00
Prop
ortio
n
0 6 12 18 24 30 36 42Time (months)
HR* = 0.61 (95%CI: 0.39-0.96)Stratified log rank p = 0.029
*adjusted by intent to use irinotecanMedian follow-up: 29.0 months
Event/N % Median (months)
R-C 37/51 73% 17.4 (10.5-20.7)
C-R 44/50 88% 11.6 (8.4-12.9)
QoL score by EQ5D
BeforeTx1
Tx14 weeks
Tx18 weeks
BeforeTx2
Tx24 weeks
Tx28 weeks
0.500.55
0.60
0.650.70
0.75
0.800.85
0.900.95
1.00
Mea
n EQ
-5D
inde
x
C-RR-C
Error bars represent 95% CI
Regorafenib
Cetuximab Cetuximab
Regorafenib
#PD-010 REVERCE QoLOS
-0.20 -0.15 -0.10 -0.05 0.00 0.05 0.10Estimate
Anorexia
Fatigue
HFSR
Rash
Adverse event
G1 vs G0G2 vs G0G1 vs G0G2 vs G0G1 vs G0G2 vs G0G1 vs G0G2 vs G0
Grade
0.001 (-0.052, 0.055)-0.061 (-0.121, -0.002)-0.030 (-0.067, 0.006)-0.106 (-0.173, -0.039)-0.004 (-0.040, 0.032)-0.025 (-0.071, 0.022)0.008 (-0.031, 0.047)0.011 (-0.043, 0.065)
Estimate (95% CI)
0.9580.0430.1060.0020.8320.3000.6860.695
P
Fatigue had the largest negative impact on QoL in patients among the four adverse events.
N=180
PD or
unacceptable
toxicities
3 wks on, 1 wk off
3 wks on, 1 wk off
T Yoshino et al. ESMO-GI 2018 #PD-010.
QoL score was comparable in two arms with lower score during regorafenib.
Group A(N=56)
Group B(N=57)
RR, %(95% Cl)
80.4(68.0-88.8)
87.7(76.4-94.2)
Group A (N=56)
Group B (N=57)
PFS rate (80% Cl), % H0: PFS rate ≤30%
46.4 (38.1-54.9) P=0.0037
47.4 (39.1-55.8) P=0.0021
Median PFSGroup A 9.1 (8.6-11.1)Group B 9.3 (6.0-13.0)
This study met primary endpoint with a PFS rate at 9 months significantly above 30% threshold.
0
20
40
60
80
100
Group A(N=56)
Group B(N=54)
*PN related AEs; Peripheral motor and sensory neuropathy
(%)
35.7%
35.7%57.4%
9.3%
66.7%71.4%
Statistical analysis• Primary endpoint: PFS rate at 9 months after
randomization• Secondary endpoints: PFS, OS, RR, TTF and safety• Sub-group: ETS, DpR, Primary tumor location
Stratification factor• Study site, age, number of metastasized organs, • response per RECIST v1.1 (CR, PR, or SD at randomization)
Key Eligibility Criteria• Aged ≥20 years, RAS wild type• Measurable lesion(s) • No previous chemotherapy• ECOG PS 0 or 1• No signs of PD within 14 daysafter the 6th cycle of treatment.
Discontinuation ofprotocol treatment
Enrollment* Randomization
1st-line mFOLFOX6 + panitumumab
6 cycles
△1
△2
△3
△4
△5
△6
△7
△△ △△ △
0 6 12 18 24Time from randomization (months) : 1 month=28 days
mFOLFOX6 + panitumumab (Group A; n=56)5-FU/LV + panitumumab (Group B; n=57)
(%)100
80
60
40
20
0
HR=0.93, 95% Cl: 0.60-1.43
0 6 18 30 36Time from randomization (months) : 1 month=28 days
12 24
*Median OS was not reached in both group.HR=1.41, 95% Cl: 0.69-2.88
mFOLFOX6 + panitumumab (Group A; n=56)5-FU/LV + panitumumab (Group B; n=57)
(%)100
80
60
40
20
0
G1≥G2
#PD-011 SAPHIRE (rP2): maintenance with FU + panitumumab
5-FU/LV plus panitumumab maintenance is better in terms of incidence of peripheral neuropathy.
M Takahashi et al. ESMO-GI 2018 #PD-011.
Group A
Group B Continue mFOLFOX6 + panitumumab
Switch to 5-FU/LV + panitumumab
Primary endpoint: PFS rate at 9months
RR
PFS OS
PN-related Aes*
• Maintenance with panitumumab alone is likely inferior than 5-FU/LV plus panitumumab in terms of PFS.
• 5-FU/LV plus panitumumab may be a preferred option.
Lessons from SAPHIRE and VALENTINO (O-016) studies
F Pietrantonio et al. ASCO 2018 #3505, ESMO-GI 2018#O-016
#PD-012 ETS and Tumor-Related Symptoms: 3 Pani Studies
Events Median months (95% CI) HR P valueETS ≥30% 205 5.0 (3.9, 7.0) 0.80 (0.66–0.97) 0.021ETS <30% 213 3.4 (2.8, 4.6)
100
80
60
40
20
00 1 2 3 4 5 6 7 8 9 10 11 12 13
Kapl
an-M
eier
est
imat
e
Time to first symptom event on study (months)
Impact of ETS on Time to New Symptomatic Event
Favours ETS ≥30% Favours ETS <30%HR
(95% CI)
ECOG PS decline
New opiate useFirst weight-loss eventNew anaemia-type eventNew asthenia-type event
Composite endpoint
10.50 1.5 2.0
AdjustedHR (95% CI) p value
0.87 (0.69–1.08)
0.71 (0.55–0.92)0.64 (0.48–0.85)0.60 (0.41–0.88)0.77 (0.60–1.00)
0.80 (0.66–0.97)
0.204
0.0090.0020.0080.049
0.021
Impact of ETS on Composite Endpoint, New Symptomatic Events and Time to ECOG Decline
Events Median months (95% CI) HR (95% CI) p valueDpR 73–100% 104 4.9 (4.1, 8.0) 0.49 (0.33, 0.73) 0.0004DpR 53–72% 104 6.0 (3.7, 7.5) 0.49 (0.33, 0.73) 0.0004DpR 31–52% 100 4.5 (3.0, 6.6) 0.55 (0.37, 0.82) 0.0037DpR 0–30% 96 2.0 (1.4, 3.2) 0.83 (0.56, 1.25) 0.3745DpR <0% 32 1.5 (0.9, 2.9)
100
80
60
40
20
00 1 2 3 4 5 6 7 8 9 10 11 12
Time to first symptom event of study (months)
Kapl
an-M
eier
est
imat
e
Impact of DpR on Time to New Symptomatic Event
3 Panitumumab Studies:PRIME + PEAK + 314
J Taieb et al. ESMO-GI 2018 #PD-012.
#PD-012 ETS and Tumor-Related Symptoms: 3 Pani Studies
Events Median months (95% CI) HR P valueETS ≥30% 205 5.0 (3.9, 7.0) 0.80 (0.66–0.97) 0.021ETS <30% 213 3.4 (2.8, 4.6)
100
80
60
40
20
00 1 2 3 4 5 6 7 8 9 10 11 12 13
Kapl
an-M
eier
est
imat
e
Time to first symptom event on study (months)
Impact of ETS on Time to New Symptomatic Event
Favours ETS ≥30% Favours ETS <30%HR
(95% CI)
ECOG PS decline
New opiate useFirst weight-loss eventNew anaemia-type eventNew asthenia-type event
Composite endpoint
10.50 1.5 2.0
AdjustedHR (95% CI) p value
0.87 (0.69–1.08)
0.71 (0.55–0.92)0.64 (0.48–0.85)0.60 (0.41–0.88)0.77 (0.60–1.00)
0.80 (0.66–0.97)
0.204
0.0090.0020.0080.049
0.021
Impact of ETS on Composite Endpoint, New Symptomatic Events and Time to ECOG Decline
Events Median months (95% CI) HR (95% CI) p valueDpR 73–100% 104 4.9 (4.1, 8.0) 0.49 (0.33, 0.73) 0.0004DpR 53–72% 104 6.0 (3.7, 7.5) 0.49 (0.33, 0.73) 0.0004DpR 31–52% 100 4.5 (3.0, 6.6) 0.55 (0.37, 0.82) 0.0037DpR 0–30% 96 2.0 (1.4, 3.2) 0.83 (0.56, 1.25) 0.3745DpR <0% 32 1.5 (0.9, 2.9)
100
80
60
40
20
00 1 2 3 4 5 6 7 8 9 10 11 12
Time to first symptom event of study (months)
Kapl
an-M
eier
est
imat
e
Impact of DpR on Time to New Symptomatic Event
3 Panitumumab Studies:PRIME + PEAK + 314
• The onset of new tumour-related symptoms was delayed in patients with RAS WT mCRC who achieved ETS ≥30% versus ETS <30%.
• Greater DpR was associated with a longer delay until the onset of new tumour-related symptoms.
• Retrospective and the symptomatic endpoints were not pre-defined; prospective trials are needed.
J Taieb et al. ESMO-GI 2018 #PD-012.
#PD-020 RAS status and Age : XELAVIRI (P3, AIO-KRK0110)
mCRCuntreated, ECOG 0-1
unresectablelesions
R1:1
StratificationLeucocytes, alkaline phosphatase, prior adjuvant therapy
FP* + Irinotecan + Bevacizumab
FP* + Irinotecan +
Bevacizumab
PDA
B
=TFS (Time to failure of strategy)
FP*+
BevacizumabN=434
<Presented as ESMO-GI 2017 #O-026/ESMO 2017#486O>
0.30 3.00
Group HR (90% CI)FAS 0.86 (0.73-1.02) NI not shown
RAS/BRAF WT 0.61 (0.46-0.82) superiority of FP+IRI+BEV
RAS MT 1.09 (0.81-1.46) NI of FP+BEVBRAF MT 1.62 (0.76-3.47) NI not shown
Cox model interaction-test for study arm *RAS status: p=0.03
Initial FP+IRI+BEV better
Initial FP+BEV better
non-inferiority
Time to failure of strategy- molecular groups
1.8 1.4
4.7
1.12.9
8.7
02468
10
All pts arm A All pts arm B
<65 yrs 65<75 yrs 75+ yrs
60-day mortality according to age
*5-FU/LV(q2w), Capecitabine(q3w)
D Modest et al. ESMO-GI 2018 #PD-020.
Group OS, monthsRAS/BRAF WT (Arm A) 25.2RAS/BRAF WT (Arm B) 32.2RAS MT (Arm A) 21.3RAS MT (Arm B) 23.2 BRAF MT (Arm A) 12.4 BRAF MT (Arm B) 7.8
Arm OS (95% CI), months
FP + BEV 21.9 (20.2-25.0)
FP+ IRI+ BEV 23.5 (20.9-27.9)
HR=0.84 (95% CI 0.66-1.06)p (log rank)=0.14
D Modest et al. ESMO-GI 2017 #O-026, ESMO 2017#486O.
0.8 1.0 3.00.3
OS
#PD-020 RAS status and Age : XELAVIRI (P3, AIO-KRK0110)
mCRCuntreated, ECOG 0-1
unresectablelesions
R1:1
StratificationLeucocytes, alkaline phosphatase, prior adjuvant therapy
FP* + Irinotecan + Bevacizumab
FP* + Irinotecan +
Bevacizumab
PDA
B
=TFS (Time to failure of strategy)
FP*+
BevacizumabN=434
<Presented as ESMO-GI 2017 #O-026/ESMO 2017#486O>
0.30 3.00
Group HR (90% CI)FAS 0.86 (0.73-1.02) NI not shown
RAS/BRAF WT 0.61 (0.46-0.82) superiority of FP+IRI+BEV
RAS MT 1.09 (0.81-1.46) NI of FP+BEVBRAF MT 1.62 (0.76-3.47) NI not shown
Cox model interaction-test for study arm *RAS status: p=0.03
Initial FP+IRI+BEV better
Initial FP+BEV better
non-inferiority
Time to failure of strategy- molecular groups
1.8 1.4
4.7
1.12.9
8.7
02468
10
All pts arm A All pts arm B
<65 yrs 65<75 yrs 75+ yrs
60-day mortality according to age
*5-FU/LV(q2w), Capecitabine(q3w)
D Modest et al. ESMO-GI 2018 #PD-020.
Group OS, monthsRAS/BRAF WT (Arm A) 25.2RAS/BRAF WT (Arm B) 32.2RAS MT (Arm A) 21.3RAS MT (Arm B) 23.2 BRAF MT (Arm A) 12.4 BRAF MT (Arm B) 7.8
Arm OS (95% CI), months
FP + BEV 21.9 (20.2-25.0)
FP+ IRI+ BEV 23.5 (20.9-27.9)
HR=0.84 (95% CI 0.66-1.06)p (log rank)=0.14
D Modest et al. ESMO-GI 2017 #O-026, ESMO 2017#486O.
0.8 1.0 3.00.3
OS• Initial FP+BEV in pts fit for intensive combination regimens cannot berecommended in pts with RAS WT mCRC.
• Intensive 1st-line chemotherapy was not associated with a substantialimprovement of outcome in pts with RAS MT mCRC.
• Overall, age subgroups did not influence TFS nor OS to a great extent (moderate prognostic impact).
• However, risk of early mortality (@60 days) appeared to rise with age.
Congratulations for your PD presentations!
Poster Discussions
“Highlights”Posters
Selection from 136 Posters
Poster Discussions Posters
“Highlights”Posters
“No-Light”Posters!?
Selection from 136 Posters
Highlights of“No-Light” posters
Poster Discussions Posters
“Highlights”Posters
Selection from 136 Posters
#P-228 VOLTAGE
#P-253 APOLLON
#P-295 DS-8201a
Radical Surgery
Without progression
Without distant
metastasis
Within 14
days
More than
14 days
Nivolumab monotherapy
Imaging/Endoscopy
Resectable
Protocol treatment
Nivolumab 2 cycles
Nivolumab 3 cycles
Postoperative adjuvant chemotherapy
(e.g., FOLFOX and XELOX)
Preoperative chemoradiotherapy (capecitabine + 50.4Gy)
Informed consentEnrollment
Imaging/Endoscopy
Imaging/Endoscopy
Imaging/Endoscopy
Diagnostic imaging
No.2post CRT, before nivolumab
• Biopsy, blood and stool collection
No.3after 3cycles of nivolumab
• Biopsy, blood and stool collection
No.1:before CRT
• Biopsy, blood and stool collection
No. 4after 5cycles of nivolumab
• Biopsy, blood and stool collection
• Surgical sample collection
Serial sample collections at 4 times
+By a local pathological assessment, *Only single cells were observed. Local pathologist diagnosed as near pCR (AJCC grade 1)
Case report: 44 year-old male (ID No. 7)From 4/Sep/2017 to 13/Oct/2017, CRT was performed (RT 50.4Gy/28Fr, Capecitabine 3000mg/day).From 24/Oct/2017 to 22/Dec/2017, 5 doses of nivolumab were administered.On 16/Jan/2018, radical surgical resection was performed.Before CRT
After CRT, before Nivo
After 3 cycles of Nivo
After 5 cycles of Nivo • Large intestine: No residual carcinoma, consistent with pCR status post-chemoradiotherapy
• lymph node: Negative for metastatic tumor(0/31)
• AJCC tumor regression: grade 0 by local pathologists.
#P-228 VOLTAGE: Nivo for LARCResectable primary rectal cancer
(cT3–4 Nany M0, Inferior margin < 12 cm from the anal verge)or
Resectable recurrent rectal cancer confined to the pelvis
ID Age/Sex
PS
Primary/Recurrent
Clinical diagnosis
MMR status
AJCC TRG pCR+ Adverse events
Nivolumab period Perioperative periodPhase Ib part
1 49/F 0 Primary T3N0M0
Stage IIpMM
RGrade
0 Yes • Pruritus: Gr1 • No AE
2 59/F 0 Primary T3N0M0
Stage IIpMM
RGrade
0 Yes • No AE • Nausea: Gr1
3 53/F 0 Primary T3N0M0
StageIIpMM
RGrade
1* No* • No AE • Gastritis: Gr2• Pain: Gr1• Extrapyramidal disorder : Gr1
Phase II part
4 48/F 0 Primary T3N1M0
Stage IIIpMM
RGrade
3 No • Pruritus: Gr1 • Back pain: Gr1
5 48/F 0 Primary T3N0M0
Stage IIpMM
RGrade
2 No• Hyperthyroidism:
Gr1• Sore throat: Gr1
• Hypothyroidism: Gr1• AST elevation: Gr2• ALT elevation: Gr3
6 59/M 0 Primary T3N0M0
Stage IIpMM
RGrade
0 Yes • Pruritus: Gr1 • No AE
7 44/M 0 Primary T3N0M0
Stage IIpMM
RGrade
0 Yes• Allergic rhinitis:
Gr1• Dry skin: Gr1• Pelvic infection: Gr3, Gastrointestinal
anastomotic leak: Gr3 →SAE• Upper respiratory infection: Gr3• Stoma site erosion: Gr2
H Bando et al. ESMO-GI 2018 #P-228.
Dosage and SchedulesPmabTAS-102
Day
Course 2
1 8 15 22 29
Course 1
6 mg/kg35 mg/m² BID
Endpoints Primary
• PFS rate at 6 monthsSecondary
• Safety: Adverse events.• Efficacy: OS, PFS, RR, DoR, DCR, TTF
Maximum % Change inTarget Lesion Size in overall
Events Median PFS 95% CI46 5.8 months 4.46-6.50
Best Overall Response RateAll, n (%) L, n (%) R, n (%)
CR 0 (0.0) 0 (0.0) 0 (0.0)PR 20 (37.0) 18(38.3) 2(28.6)SD 24 (44.4) 22(46.8) 3(28.6)PD 11 (18.5) 7(14.9) 3(42.9)RR 20 (37.0) 18(38.3) 2(28.6)DCR 44 (81.5) 40 (85.1) 4 (57.1)
At risk
L: Left-sided tumors (N=47), R: Right-sided tumors (N=7)
100
80
60
40
20
0
PFS
rate
(%)
0 3 6 9 1254 41 26 7 0
% re
duct
ion
175
125
100
75
50
150
302010
0-10-20-30-50
-75
-100
PDSDPR
PFS in over all
(N=54)
Maximum % Change inTarget Lesion Size by TL(Left, N=47; Right, N=7)
PFS by primary tumor location(Left, N=47; Right, N=7)
#P-253 APOLLON (P1/2): TAS-102 + Panitumumab
K Yamazaki et al. ESMO-GI 2018 #P-253.
DS-8201a Structure and Mechanism of Action (MoA)
12
3
45
6
7
Propriety drug-linker and payload
Conjugation chemistryThe linker is connected to the cysteine residue of the antibody
Payload (Dxd)Exatecan derivative
Cysteine residueDrug-Linker
Cys
Study Design
HER2-statuscentrally
confirmed
HER2-positive mCRC (IHC 3+ or IHC 2+/ISH+)
DS-8201a 6.4 mg/kg q3wkn=50
Cohort A
HER2-expressing mCRC(IHC 2+/ISH-)
DS-8201a 6.4 mg/kg q3wkn =20
Cohort B
HER2-expressing mCRC(IHC 1+)
DS-8201. 6.4 mg/kg q3wkn=20
Cohort C
Cohorts B and C will open for enrollment depending on therisk/benefit assessment in cohort A
Efficacy Outcomes with DS-8201a in HER2-expressing Solid Tumors in the Ongoing Phase 1 Trial (April, 2018 cutoff)5
ConfirmedORRa
Confirmed DCRa
(95% CI)aPFS Median(95% CI), mo
HER2+ breast cancerb 54.5% (54/99) 93.9% (93/99) NR
HER2+ gastric cancerb 43.2% (19/44) 79.5% (35/44) 5.6 (3.0, 8.3)
Other HER2-expressing/mutated 38.7% (12/31) 83.9% (26/31) 12.1 (2.7, 14.1)
aSubjects who had ≥2 postbaseline scans, had progressive disease, or discontinued treatment for progressive disease or any other reason prior to second postbaseline scan.bIHC 3+ or IHC2+ and ISH+.
Primary Endpoint Secondary Efficacy Endpoints
• ORR (proportion who achieved a best overall response of CR or PR) assessed by the independent radiologic facility review based on RECIST version 1.1 in Cohort A
• OS • PFS • DCR • DoR• ORR based on RECIST version
1.1 in Cohorts B and C • ORR assessed by the
investigator based on RECIST version 1.1
.
8
Doi T, et al. Lancet Oncol. 2017, Iwata H, et al ASCO 2018
-1 0 0
-8 0
-6 0
-4 0
-2 0
0
2 0
4 0
6 0
8 0
Ch
an
ge
fro
m b
ase
line
(%
)C o lo re c ta l
N S C L C
O th e r
Other Cancers
N = 37
0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0-1 0 0
-8 0
-6 0
-4 0
-2 0
0
2 0
4 0
6 0
8 0
1 0 0
W e e k s
Cha
nge
from
bas
elin
e (%
)
C o lo re c ta l
N S C L C
O th e r
Payload with a different MoA High potency of payload Payload with short systemic half-life Bystander effect Tumor-selective cleavable linker Stable linker-payload High drug-to-antibody ratio
T Yoshino et al. ESMO-GI 2018 #P-295.
#P-295 DS-8201a for mCRC Trial in progress
Thank you for your kind attention!!!