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

Authors
Ku, G.Elimova, E.Denlinger, C. S.Mehta, R.Lee, K-W.Iqbal, S.Kang, Y-K.Oh, D-Y.Rha, S. Y.Kim, Y. H.Seol, Y. M.Mwatha, T.Grim, J.Ajani, J. A.
Issue Date
Sep-2021
Publisher
Oxford University Press
Citation
Annals of Oncology, v.32, no.Suppl 5, pp S1044 - S1045
Indexed
SCIE
SCOPUS
Journal Title
Annals of Oncology
Volume
32
Number
Suppl 5
Start Page
S1044
End Page
S1045
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/54488
DOI
10.1016/j.annonc.2021.08.1489
ISSN
0923-7534
1569-8041
Abstract
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. 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; Finan
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