Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with chemotherapy (chemo) and tislelizumab (TIS) as first-line (1L) therapy for patients (pts) with advanced HER2-positive gastric/gastroesophageal junction adenocarcinoma (G/GEJC): Preliminary results from a phase 1b/2 study.
Keun Wook Lee, Li‐Yuan Bai, Minkyu Jung, Jieer Ying, Young Hyuck Im, Do‐Youn Oh, Y. Choi, Sang Cheul Oh, Yee Chao, Huiyan Li, Ping Zhou, Yuanyuan Bao, Yoon‐Koo Kang
Abstract
4032 Background: Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that targets two distinct extracellular domains of HER2. Zani has shown preliminary antitumor activity and tolerability in pts with HER2+ gastroesophageal adenocarcinoma as monotherapy/with chemo in Phase 1/2 studies (NCT02892123, NCT03929666). TIS, an anti-PD-1 antibody, has demonstrated antitumor activity in pts with advanced solid tumors. Combining anti-HER2 therapy with anti-PD-1 therapy and chemo increased tumor response in G/GEJC in a Phase 3 clinical trial. Methods: Cohort 2 of this ongoing open-label, Phase 1b/2 study was in pts with untreated locally advanced/metastatic HER2+ G/GEJC (NCT04276493). Cohort A received zani 30 mg/kg IV, Cohort B received zani 1800 mg IV (weight < 70 kg) or 2400 mg IV (weight ≥ 70 kg), both with TIS 200 mg IV and capecitabine/oxaliplatin (CAPOX) Q3W. Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS). Results: As of Nov 26, 2021, 33 pts with a median age of 64.0 years (range: 29.0–80.0) were assigned to Cohort A (n=19) or B (n=14). Median study follow-up was 7.7 months (range: 2.1–19.0) and the median number of treatment cycles was 10 (range: 1–28), 20 (60.6%) pts remained on treatment. All pts were efficacy evaluable ([EE], n=33), confirmed ORR was 72.7% (95% CI: 54.5, 86.7). Median PFS was 10.9 months (95% CI: 6.9, NE). Efficacy data are summarized in the Table. All pts experienced ≥ 1 treatment emergent adverse event (TEAE), and 24 (72.7%) pts experienced ≥ Grade 3 TEAEs. All pts experienced treatment related TEAEs (trTEAEs), 20 (60.6%) pts experienced ≥ Grade 3 trTEAEs and trTEAEs leading to death occurred in two (6.1%) pts. Immune-mediated AEs (imAEs) occurred in nine (27.3%) pts, of which seven (21.2%) pts experienced ≥ Grade 3 imAEs. Conclusions: Zani, TIS and CAPOX combination demonstrated a manageable safety profile and antitumor activity as 1L therapy for pts with HER2+ G/GEJC. Clinical trial information: NCT04276493. [Table: see text]