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

Abstract

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. 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.