1518P - Zanidatamab (zani) plus chemotherapy (chemo) and tislelizumab (tis) as first-line (1l) therapy for patients (pts) with advanced HER2-positive (+) gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a phase Ib/II study

Background

Zani, an anti-HER2 bispecific antibody, targets two distinct extracellular domains of HER2 and has shown preliminary antitumor activity and tolerability, with chemo, in pts with HER2+ GC/GEJC. These are updated results from the phase Ib/II study (NCT04276493) for zani plus chemo and TIS, an anti-PD-1 monoclonal antibody. Duration of response is reported for the first time.

Methods

Cohort 2 of this open-label study included pts with untreated, unresectable, locally advanced/metastatic HER2+ GC/GEJC. Cohort 2a received zani 30 mg/kg intravenously (IV), Cohort 2b received zani 1800 mg IV (weight <70 kg) or 2400 mg IV (weight ≥70 kg), each with TIS 200 mg IV every 3 weeks. Both cohorts also received standard capecitabine-oxaliplatin (CAPOX). Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed progression-free survival (PFS), duration of response, and disease control rate.

Results

As of 22 Nov 2022, 33 pts (median age 64 years [range: 29-80]) were assigned to Cohort 2a (n=19) or 2b (n=14). Overall, 13 (39.4%) pts remained on treatment. Confirmed ORR was 75.8% (95% CI: 57.7, 88.9); median PFS was 16.7 months (95% CI: 8.2, NE). Efficacy data are presented in the table. All pts had ≥1 treatment-related adverse event (TRAE), and 22 (66.7%) had grade ≥3 TRAEs. Serious TRAEs occurred in 11 (33.3%) pts; TRAEs leading to treatment discontinuation occurred in two (6.1%) pts; and TRAEs leading to death occurred in two (6.1%) pts.

Table: 1518P

^a Confirmed. DCR, disease control rate; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival.

Conclusions

Zani plus TIS and CAPOX produced durable, promising antitumor activity with encouraging PFS as 1L therapy for pts with HER2+ GC/GEJC. Safety was consistent with previous findings. A phase III trial (NCT05152147) evaluating this regimen is ongoing.

Clinical trial identification

NCT04276493.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Emily Finn, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

K. Lee: Financial Interests, Personal, Advisory Board: BMS (Korea), Bayer (Korea), Daiichi Sankyo (Korea), Merck Sharp & Dohme (Korea), Metafines, Vifor pharma (Korea), Astellas (Korea); Financial Interests, Personal, Invited Speaker: Boryung Co.; Financial Interests, Institutional, Local PI: ABL Bio, ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bolt therapeutics, Daiichi Sankyo, Exelixis, Genexine, Green Cross Corp, InventisBio, LSK BioPharma, Leap therapeutics, MacroGenics, MedPacto, Merck KGaA, Merck Sharp & Dohme, Oncologie, Ono pharmaceutical, Y-Biologics, Pfizer, Pharmacyclics, Seagen, Taiho Pharmaceutical, Trishula Therapeutics, Zymeworks; Non-Financial Interests, Leadership Role, SMC chair of ASPEN-06 study: ALX Oncology. M. Jung: Financial Interests, Advisory Role: Cartexell Inc. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck, 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. P. Zhou, Y. Bao: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, MacroGenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, LISCure. All other authors have declared no conflicts of interest.