th World Congress on Gastrointestinal Cancer, Barcelona … · 2018. 7. 9. · Safety of...

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


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)


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



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


Selection from 136 Posters

Poster Discussions Posters


“No-Light”Posters!?


Highlights of“No-Light” posters

Poster Discussions 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


No.1:before CRT


No. 4after 5cycles of nivolumab


• 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


Stage IIpMM

RGrade

0 Yes • No AE • Nausea: Gr1


StageIIpMM

RGrade

1* No* • No AE • Gastritis: Gr2• Pain: Gr1• Extrapyramidal disorder : Gr1

Phase II part


Stage IIIpMM

RGrade

3 No • Pruritus: Gr1 • Back pain: Gr1


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

[email protected]

Thank you for your kind attention!!!

th World Congress on Gastrointestinal Cancer, Barcelona … · 2018. 7. 9. · Safety of...

Documents

Transcript of th World Congress on Gastrointestinal Cancer, Barcelona … · 2018. 7. 9. · Safety of...