In a phase II trial reported in The Lancet Oncology, Elimova et al evaluated the efficacy and safety of the bispecific monoclonal antibody zanidatamab plus chemotherapy in the first-line treatment of patients with advanced HER2-positive gastroesophageal adenocarcinoma.
Study Details
In the trial, 46 patients from sites in Canada, South Korea, and the United States, enrolled between August 2019 and February 2022, received zanidatamab plus CAPOX (capecitabine, oxaliplatin; n = 20), FP (fluorouracil [5-FU], cisplatin; n = 2), or modified FOLFOX6 (mFOLFOX6; leucovorin, 5-FU, and oxaliplatin; n = 24). In the CAPOX and FP groups, patients received either 30 mg/kg of zanidatamab or 1,800 or 2,400 mg (patients weighing < 70 or ≥ 70 kg) every 3 weeks. In the mFOLFOX6 group, patients received either 20 mg/kg of zanidatamab or 1,200 or 1,600 mg (patients weighing < 70 or ≥ 70 kg) every 2 weeks.
Key Findings
Median follow-up was 47.9 months (interquartile range = 39.2–53.7 months). Among 42 evaluable patients, confirmed objective responses were observed in 32 patients (76.2%, 95% CI = 60.5%–87.9%), with complete responses in 3 (7%). Median duration of response was 18.7 months (95% CI = 10.4–44.1 months). The disease control rate was 88.1% (95% CI = 74.4%–96.0%). Median progression-free survival was 12.5 months (95% CI = 8.2–21.8 months), and median overall survival was 36.5 months (95% CI = 23.6 months to not estimable).
Treatment-related grade 3 or 4 adverse events occurred in 65% of patients, most commonly diarrhea (39%, including in 5 of 21 patients after implementing mandatory antidiarrheal prophylaxis), hypokalemia (22%), and vomiting (9%). Serious treatment-related adverse events occurred in 17% of patients, most commonly diarrhea (7%). Adverse events led to the discontinuation of zanidatamab in 13% of patients. No treatment-related deaths were observed.
The investigators concluded: “Zanidatamab plus chemotherapy as first-line treatment of HER2-positive advanced gastro-oesophageal adenocarcinoma demonstrated clinically meaningful and durable antitumour activity, with a manageable safety profile.”
Elena Elimova, MD, of Princess Margaret Cancer Centre, Toronto, Canada, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Jazz Pharmaceuticals and Zymeworks. For full disclosures of all study authors, visit The Lancet Oncology.
