134O - Asia subgroup overall survival and long-term follow-up results of the phase IIb HERIZON-BTC-01 study: Zanidatamab in previously treated human epidermal growth factor receptor 2 (HER2)-amplified biliary tract cancer (BTC)

Background

In patients with previously treated HER2+ BTC, HER-2 targeted zanidatamab demonstrated a meaningful clinical benefit with a manageable safety profile in the overall population and Asia subgroup (HERIZON-BTC-01 trial, NCT04466891).¹ Here, we report updated analyses and overall survival for Cohort 1 (HER2-amplified with either immunohistochemistry 2+ or 3+) from the Asia subgroup (China and South Korea).

Methods

This open-label, phase IIb study enrolled adults with HER2-amplified, unresectable, locally advanced/metastatic BTC, and ≥1 prior gemcitabine-containing systemic therapy. Patients received zanidatamab monotherapy (20 mg/kg IV Q2W). Primary endpoint: confirmed objective response rate. Select secondary endpoints: duration of response, progression-free survival, overall survival, and adverse events.

Results

Cohort 1 enrolled 50 patients from Asia. Baseline demographic and disease characteristics were stated previously.¹ As of July 28, 2023, 4 patients (8%) remained on treatment; median study follow-up was 20.8 months (range 16.5-31.9). Efficacy data is in Table. Thirty-five patients (70%) experienced ≥1 treatment-related adverse events (TRAEs); most common were infusion-related reaction (42%) and diarrhea (28%). Seven patients (14%) experienced ≥1 grade 3 or higher TRAEs, most common was ejection fraction decreased (4%); 3 patients (6%) experienced serious TRAEs. One patient (2%) had a TRAE leading to treatment discontinuation; no TRAE leading to death was reported.

Conclusions

With longer follow-up, zanidatamab demonstrated extended response with an encouraging median overall survival for patients from Asia with previously treated HER2+ BTC and remained well tolerated with manageable adverse events. ¹Sun H. et al. Ann Oncol. 2023;34:S1522-1523 (cutoff: 10 Oct 2022). Table: 134O

^aConfirmed by independent central review per RECIST v1.1. 95% CI estimated using methods:^bClopper-Pearson exact binomial.^cBrookmeyer & Crowley with log-log transformation.^dGreenwood. CI, confidence interval.

Clinical trial identification

NCT04466891.

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Rania Kairouz-Wahbe, PhD, and Renee E. Granger, PhD, of Envision Pharma Inc., and was funded by BeiGene.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

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, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. H. Sun: Financial Interests, Personal and Institutional, Research Grant: BeiGene, Chiatai Tianqing, Eisai, Innovent, MSD, and Roche; Financial Interests, Personal, Speaker, Consultant, Advisor, ; consulting fees and honoraria: AstraZeneca, Bayer, Eisai, Hengrui, MSD, and Roche; Financial Interests, Personal, Other, travel support: MSD, and Roche; Financial Interests, Personal, Other, receipt of equipment, materials, drugs, medical writing, gifts or other services: Innovent, MSD, and Roche. J.W. Kim: Financial Interests, Personal and Institutional, Research Grant: Inno.N, and Jeil Pharm; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, ONO, Sanofi-Aventis, Servier, and TCUBEit. X. Wu: Financial Interests, Institutional, Full or part-time Employment: Jazz Pharmaceuticals, Inc. Y. Bao: Financial Interests, Institutional, Full or part-time Employment: BeiGene (Beijing) Co., Ltd; Financial Interests, Personal, Stocks or ownership: BeiGene (Beijing) Co., Ltd. P. Garfin: Financial Interests, Institutional, Full or part-time Employment: Jazz Pharmaceuticals, Inc., and Zymeworks, Inc. Y. Zhao: Financial Interests, Institutional, Full or part-time Employment: BeiGene (Beijing) Co., Ltd; Financial Interests, Personal, Stocks/Shares: BeiGene (Beijing) Co., Ltd. All other authors have declared no conflicts of interest.