The human monoclonal antibody sugemalimab is a safe and effective consolidation therapy for patients with unresectable stage III non–small cell lung cancer (NSCLC) without disease progression after either concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (sCRT), according to findings presented by Wu et al at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2022 (Abstract OA02.05).
Sugemalimab is a full-length, fully human IgG4 monoclonal antibody targeting PD-L1. GEMSTONE-301 is an ongoing phase III trial to evaluate sugemalimab as a consolidation treatment in patients with unresectable stage III NSCLC without disease progression following chemoradiotherapy. The trial is the first phase III study in this setting to include patients who received either concurrent or sequential chemoradiotherapy.
Previously, in the preplanned progression-free survival interim analysis, sugemalimab showed a statistically significant and clinically meaningful improvement in progression-free survival compared with placebo. To follow up on this previous work, Yi-Long Wu, MD, of Guangdong Provincial People's Hospital in Guangzhou, China, and colleagues finished a preplanned progression-free survival final analysis.
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Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status 0 vs 1, chemoradiotherapy type (cCRT vs sCRT), and total radiotherapy dose (< 60 Gy vs ≥ 60 Gy). The primary endpoint was progression-free survival by blinded independent central review. Secondary endpoints included overall survival, investigator-assessed progression-free survival, overall response rate, and duration of response. Overall survival is a key secondary endpoint with protocol prespecified analysis.
As of the progression-free survival final analysis, 62 (24.3%) patients in the sugemalimab group and 26 (20.6%) patients in the placebo group remain under study in the ongoing trial. The median follow-up duration was 27.1 and 23.5 months, respectively.
The median progression-free survival assessed by independent central review was 10.5 months in the sugemalimab group vs 6.2 months in the placebo group (stratified hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.50–0.84). The 24- and 36-month progression-free survival rates were 38.6% vs 23.1% and 26.1% vs 0%, respectively. Consistent progression-free survival benefit was observed with sCRT (HR = 0.57, median progression-free survival = 8.1 vs 4.1 months) and cCRT (HR = 0.71, median progression-free survival = 15.7 vs 8.3 months). Median overall survival was not reached in the sugemalimab group vs 25.9 months in the placebo group (HR = 0.69, 95% CI = 0.49–0.97), sCRT (HR = 0.60, median overall survival = not reached vs 24.1 months) and cCRT (HR = 0.75, median overall survival = not reached vs 32.4 months). The 24- and 36-month overall survival rates were 67.6% vs 55.0% (sCRT = 70.7% vs 53.7%; cCRT = 66.3% vs 57.6%) and 55.8% vs 29.5% (sCRT = 59.0% vs 43.7%; cCRT = 54.1% vs 19.8%), respectively. Grade ≥ 3 treatment-related adverse events occurred in 11.4% vs 5.6% of patients treated with sugemalimab and placebo, respectively.
“Sustained progression-free survival benefits and [a] well-tolerated safety profile were observed in this progression-free survival final analysis, [and] preliminary overall survival data showed a trend for benefit favoring sugemalimab,” Dr. Wu said. “The results provide evidence that sugemalimab is a safe and effective consolidation therapy for patients with unresectable stage III NSCLC without disease progression after either cCRT or sCRT. In June 2022, sugemalimab was approved for this indication in China.”
