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ePoster Display

1380P - Phase (Ph) II study of zanidatamab + chemotherapy (chemo) in first-line (1L) HER2 expressing gastroesophageal adenocarcinoma (GEA)

Date

16 Sep 2021

Session

ePoster Display

Presenters

Geoffrey Ku

Citation

Annals of Oncology (2021) 32 (suppl_5): S1040-S1075. 10.1016/annonc/annonc708

Authors

G. Ku1, E. Elimova2, C.S. Denlinger3, R. Mehta4, K. Lee5, S. Iqbal6, Y. Kang7, D. Oh8, S.Y. Rha9, Y.H. Kim10, Y.M. Seol11, T. Mwatha12, J. Grim12, J.A. Ajani13

Author affiliations

  • 1 Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2 Medical Oncology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 3 Department Of Hematology/oncology, Fox Chase Cancer Center, Philadelphia/US
  • 4 Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 5 Department Of Internal Medicine, 5. Seoul National University College of Medicine, Seoul National University Bundang Hospital, 13620 - Seongnam/KR
  • 6 Medical Oncology, University of Southern California, Los Angeles/US
  • 7 Department Of Oncology, Asan Medical Center, Seoul/KR
  • 8 Medical Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul/KR
  • 9 Dept. Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 10 Department Of Biomedical Sciences, Korea University Anam Hospital, Seoul/KR
  • 11 Department Of Internal Medicine, Pusan National University Hospital, Busan/KR
  • 12 Clinical Development, Zymeworks Inc, Vancouver/CA
  • 13 Gi Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
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Abstract 1380P

Background

Metastatic HER2-expressing GEA has limited treatment options and high morbidity and mortality. Zanidatamab (zani), a HER2-targeted bispecific antibody also known as ZW25, was well-tolerated with durable responses (33% confirmed objective response rate [cORR] as monotherapy; 54% cORR with chemo) in patients (pts) with heavily pre-treated metastatic HER2-expressing GEA in a Ph 1 study.

Methods

In this ongoing Ph 2 trial (NCT03929666), pts with untreated locally advanced/metastatic HER2-expressing GEA are treated with physician’s choice of zani + 5FU/leucovorin/oxaliplatin (mFOLFOX6) every 2 weeks, or zani + capecitabine/oxaliplatin (CAPOX) or 5FU/cisplatin (FP) every 3 weeks. Primary objectives are to evaluate safety and antitumor activity. Response assessments are performed every 6 weeks per RECIST 1.1.

Results

As of Mar 18, 2021, 30 pts have been treated (zani + either mFOLFOX6 [14], CAPOX [14], or FP [2]; male: 87%; median age: 58 yrs). The median treatment duration was 9 cycles (range, 1-20) and 14 pts remain on treatment. All pts had a treatment-related (zani and/or chemo) adverse event (TRAE), the majority of which were Grade (Gr) 1 or 2 in severity; the most common (≥25% pts) were diarrhea, nausea, peripheral sensory neuropathy, fatigue, decreased appetite, vomiting, and hypokalemia. TRAEs with Gr 3 as the highest grade were reported in 66% of pts overall (79% zani + mFOLFOX6; 57% zani + CAPOX; 50% zani + FP); the most common (≥10% pts) were diarrhea (43%), hypokalemia (10%), and vomiting (10%). 7% experienced Gr 4 TRAEs (hypokalemia and leukopenia) and 10% discontinued treatment due to TRAEs (all in zani + mFOLFOX6). There were no treatment-related deaths. In 22 HER2+ (IHC3+ or ISH+/IHC2+) response-evaluable pts, the cORR was 68.2% and the disease control rate was 90.9%. For the 15 pts with confirmed responses, the duration ranged from 1.4 to 15.4 months, with 10 responses ongoing.

Conclusions

Zanidatamab with standard 1L chemo shows an encouraging cORR and response durability in pts with HER2+ GEA with a manageable safety profile. Based on these results, a global Ph 3 study in 1L HER2+ GEA is planned to evaluate zani + chemo (CAPOX or FP) ± the PD-1 inhibitor tislelizumab.

Clinical trial identification

NCT03929666.

Editorial acknowledgement

Legal entity responsible for the study

Zymeworks Inc.

Funding

Zymeworks Inc.

Disclosure

G. Ku: Financial Interests, Personal, Advisory Board: Apexigen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pieris; Financial Interests, Personal, Advisory Board: Zymeworks; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: Arog; Non-Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Non-Financial Interests, Institutional, Principal Investigator, Local PI: Daiichi Sankyo; Non-Financial Interests, Institutional, Principal Investigator, Local PI: Merck; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: Oncolys; Non-Financial Interests, Institutional, Principal Investigator, Local PI: Pieris; Non-Financial Interests, Institutional, Principal Investigator, Local PI: Zymeworks. E. Elimova: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Zymeworks; Financial Interests, Institutional, Other, Consulting: Adaptimmune; Non-Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Non-Financial Interests, Institutional, Principal Investigator, Local PI: Zymeworks; Non-Financial Interests, Institutional, Principal Investigator, Steering Committee Member: Zymeworks; Financial Interests, Personal, Other, Spouse employee of Merck Vaccines: Merck. C.S. Denlinger: Financial Interests, Personal, Advisory Board: Bristol Myer Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Other, Data Safety Monitoring Board: Zymeworks; Financial Interests, Personal, Advisory Board, RFP development team: Taiho Oncology; Financial Interests, Personal, Advisory Board, RFP development team: Eli Lilly & Co; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Institutional, Invited Speaker, Local PI: MedImmune; Financial Interests, Institutional, Invited Speaker, Local PI: Amgen; Financial Interests, Institutional, Invited Speaker, Local PI: Array BioPharma; Financial Interests, Institutional, Invited Speaker, Local PI: Agios Pharmaceuticals; Financial Interests, Institutional, Invited Speaker, Local PI: AstraZeneca; Financial Interests, Personal and Institutional, Other, Steering Committee Member: BeiGene; Financial Interests, Institutional, Invited Speaker, Local PI: Bristol Myer Squibb; Financial Interests, Institutional, Invited Speaker, Local PI: Zymeworks; Financial Interests, Institutional, Invited Speaker, Local PI: Exelixis; Financial Interests, Institutional, Invited Speaker, Local PI: Genmab; Financial Interests, Institutional, Invited Speaker, Local PI: BeiGene. R. Mehta: Financial Interests, Personal, Other, Paid consultant: Eli Lilly; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Natera. K. Lee: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Consultation: ISU ABXIS; Financial Interests, Institutional, Principal Investigator, Local PI: ABLBIO; Financial Interests, Institutional, Principal Investigator, Local PI: ALX Oncology; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: BeiGene; Financial Interests, Institutional, Principal Investigator, Local PI: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator, Local PI: Five Prime Therapeutics; Financial Interests, Institutional, Principal Investigator, Local PI: Genexine; Financial Interests, Institutional, Principal Investigator, Local PI: Green Cross Corp; Financial Interests, Institutional, Principal Investigator, Local PI: LSK BioPharma; Financial Interests, Institutional, Principal Investigator, Local PI: Macrogenics; Financial Interests, Institutional, Principal Investigator, Local PI: Merck KGaA; Financial Interests, Institutional, Principal Investigator, Local PI: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator, Local PI: Oncologie; Financial Interests, Institutional, Principal Investigator, Local PI: Ono pharmaceutical; Financial Interests, Institutional, Principal Investigator, Local PI: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Pharmacyclics,; Financial Interests, Institutional, Principal Investigator, Local PI: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator, Local PI: Y-BIOLOGICS; Financial Interests, Institutional, Principal Investigator, Local PI: Zymeworks. S. Iqbal: Financial Interests, Personal, Advisory Board, Advisory board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Speaker series to BeiGene faculty on esophageal cancer: BeiGene; Financial Interests, Personal, Advisory Board: Eisai. Y. Kang: Financial Interests, Personal, Other, Consultant: ALX Oncology; Financial Interests, Personal, Other, Consultant: Zymeworks; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Other, Consultant: Daehwa; Financial Interests, Personal, Other, Consultant: Blueprint; Financial Interests, Personal, Other, Consultant: Surface Oncology; Financial Interests, Personal, Other, Consultant: BMS; Financial Interests, Personal, Other, Consultant: Merck (MSD). D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: ASLAN; Financial Interests, Personal, Advisory Board: Halozyme; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Advisory Board: BMS/Celgene; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Advisory Board: Turning Point; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Array; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Servier; Financial Interests, Personal, Research Grant: BeiGene; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Handok. S.Y. Rha: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Daichii Sankyo; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Indivumed; Financial Interests, Institutional, Funding: Celltrion; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Personal, Other, Drug supply for preclinical study: Daichii sankyo. T. Mwatha: Financial Interests, Personal, Full or part-time Employment: Zymeworks Inc; Financial Interests, Personal, Stocks/Shares: Zymeworks Inc. J. Grim: Financial Interests, Personal, Writing Engagements, ASCO Ed Book Chapter Author: ASCO; Financial Interests, Personal, Other, ASCO Ed Comm Membership: ASCO; Financial Interests, Personal, Invited Speaker, CME talk: Prime Education; Financial Interests, Personal, Full or part-time Employment, Medical Director since July 2020: Zymeworks; Financial Interests, Personal, Member of the Board of Directors, Board Member through July 2020: Assoc. for VA Hematology Oncology; Financial Interests, Personal, Stocks/Shares, Spouse IRA: Medtronic; Financial Interests, Personal, Stocks/Shares, Retirement Account: Vanguard Mutual Fund; Financial Interests, Personal, Principal Investigator, Local PI until 7/2020: Pfizer; Financial Interests, Personal, Principal Investigator, Local PI until 7/2020: Merck; Financial Interests, Personal and Institutional, Principal Investigator, Local PI until 7/2020; covered travel to investigator meeting: RenovoRx. J.A. Ajani: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Grail; Financial Interests, Personal, Advisory Board: Turning Point; Non-Financial Interests, Institutional, Invited Speaker, Local PI: BMS; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Merck; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Astellas; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Taiho; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Delta Fly; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Roche; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Prolynx; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Zymeworks; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Daiichi; Non-Financial Interests, Institutional, Invited Speaker, Local PI: LEAP; Non-Financial Interests, Institutional, Invited Speaker, Local PI: Gilead. All other authors have declared no conflicts of interest.

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