132MO - Zanidatamab (ZW25; Zani) in patients (pts) with previously treated advanced human epidermal growth factor receptor 2 (HER2)-amplified biliary tract cancer (BTC): Asia subgroup analysis of the phase IIb HERIZON-BTC-01 study

Background

Zani, a HER2-targeted bispecific antibody, has shown antitumor activity and a tolerable and manageable safety profile in pts with HER2-amplified, treatment (Tx)-refractory, advanced BTC (HERIZON-BTC-01; NCT04466891). Here, we report a post-hoc analysis of the Asia subgroup in predetermined cohort 1 (HER2 immunohistochemistry 2+ or 3+) comprising pts from China and South Korea.

Methods

This phase 2b, open-label, single-arm study evaluated Zani monotherapy (20 mg/kg IV Q2W) in adults with HER2-amplified, inoperable, locally advanced/metastatic BTC. Pts had received ≥1 prior systemic Tx for advanced disease, including gemcitabine. The primary endpoint was confirmed objective response rate. Secondary endpoints included disease control rate, duration of response, progression-free survival, and adverse events (AEs).

Results

Of 80 pts enrolled in cohort 1, 50 were from Asia (median age 63.5 years; 29 [58%] gallbladder cancer, 11 [22%] intra-, and 10 [20%] extra-hepatic cholangiocarcinoma). At data cutoff (Oct 10, 2022), median study follow-up was 11.3 months (range 6.9-22.3); 7 (14%) pts remained on Tx. Pts had median 1 prior line (range 1-5) of Tx for advanced disease. Efficacy is summarized in the table. Tx-related AEs (TRAEs) were experienced by 70% of pts, the most common being infusion-related reactions (42%), diarrhea (28%), and decreased ejection fraction (EF; 12%). In all, 10% of pts experienced grade 3 TRAEs (decreased EF [4%]; diarrhea, increased blood bilirubin, and enteritis [all 2%]); none had grade 4/5 TRAEs. A total of 4% of pts had serious TRAEs and 2% discontinued Tx due to decreased EF. Table: 132MO

CI, confidence interval^aConfirmed by independent central review per RECIST v1.1; ^bEstimated using Clopper-Pearson method; ^cEstimated using Brookmeyer & Crowley method with log-log transformation.

Conclusions

Zani demonstrated durable tumor responses and a tolerable and manageable safety profile in pts in the Asia subgroup with Tx-refractory HER2-amplified advanced BTC, consistent with the overall study population (Harding J, et al. Lancet Oncol. 2023).

Clinical trial identification

NCT04466891; July 10, 2020.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Saxony Olivier, MMed For Path (SA), of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd. and Zymeworks Inc.

Disclosure

H. Sun: Non-Financial Interests, Institutional, Membership or affiliation: China anti-cancer association. J.W. Kim: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, Ono, Sanofi-Aventis, Servier, TCUBEit; Non-Financial Interests, Institutional, Research Funding: Inno.N, Jeil Pharm. H. Chang: Financial Interests, Institutional, Local PI: BeiGene, Ltd., Senhwa biosciences, Taiho Oncology, Astellas Pharma Global Development, AbbVie. J. Ying: Financial Interests, Institutional, Stocks/Shares: BeiGene. Ltd. M.A. Lee: Non-Financial Interests, Institutional, Local PI: Taiho, GSK, Astellas, MSD, AstraZeneca, Exellis, Novartis, Janssen, D3 Bio, Inventis Bio, Ipsen, Boston Pharm, Meta Fines, Phanolos, Amgen, Mirati Therapeutics, Novocure; Non-Financial Interests, Personal, Principal Investigator: Boryeong, Inno.N; Non-Financial Interests, Personal, Speaker, Consultant, Advisor: Handok, GI innovation. T. Song: Financial Interests, Institutional, Advisory Board: BeiGene. Ltd. H. Pan, G. Yu, Q. Yan: Financial Interests, Institutional, Stocks/Shares: BeiGene. Ltd. X. Wu: Financial Interests, Institutional, Full or part-time Employment: Jazz Pharmaceuticals. Y. Bao, J. Ma: Financial Interests, Institutional, Full or part-time Employment: BeiGene Ltd; Financial Interests, Institutional, Stocks/Shares: BeiGene Ltd. P. Garfin: Financial Interests, Personal, Full or part-time Employment: Jazz Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Jazz Pharmaceuticals, Seagen. J. Fan: Financial Interests, Personal, Coordinating PI: Regional leading PI, BeiGene co-sponsored ZWI-ZW25-203; Financial Interests, Personal, Principal Investigator: BeiGene co-sponsored ZWI-ZW25-203; Financial Interests, Personal, Steering Committee Member: BeiGene co-sponsored ZWI-ZW25-203. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. All other authors have declared no conflicts of interest.