In a Japanese phase II study (NO LIMIT, WJOG13320G) reported in the Journal of Clinical Oncology, Kawakami et al evaluated whether first-line nivolumab plus low-dose ipilimumab showed activity in patients with microsatellite instability–high (MSI-H) advanced gastric/esophagogastric junction cancer.
Study Details
In the multicenter trial, 29 patients enrolled between November 2020 and August 2022 were treated with nivolumab at 240 mg every 2 weeks and ipilimumab at 1 mg/kg every 6 weeks for up to 24 months or until disease progression or unacceptable toxicity. The primary endpoint was overall response rate on blinded independent central review.
Key Findings
Objective responses were observed in 18 patients (62.1%, 95% confidence interval [CI] = 42.3%–79.3%), with complete responses in 3 (10.3%). The disease control rate was 79.3% (95% CI = 60.3%–92.0%). Median duration of response was not reached (95% CI = 12.6 months to not reached).
Treatment-related adverse events of any grade occurred in 93.1% of patients; events were grade ≥3 in 37.9%, most commonly hypopituitarism (6.9%) and maculopapular rash (6.9%).
At a median follow-up of 9.0 months, treatment had been discontinued due to treatment-related adverse events in 12 patients (41.4%). With the exclusion of 1 patient with progressive disease, antitumor activity was maintained in the other 11 patients after discontinuation for a range of 0.9 to 15.6 months.
Median progression-free survival was 13.8 months (95% CI = 13.7 months to not reached). Median overall survival was not reached (95% CI = 13.7 months to not reached), with a 12-month rate of 79.5%.
The investigators concluded: “[Nivolumab plus low-dose ipilimumab] showed robust and durable antitumor efficacy as a first-line treatment for MSI-H [advanced gastric/esophagogastric junction cancer]. Although [treatment-related adverse events] often led to treatment discontinuation, treatment efficacy was subsequently sustained in most patients.”
Hisato Kawakami, MD, PhD, of the Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-sayama, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb Co Ltd. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
