The human monoclonal antibody sugemalimab is a safe and effective consolidation therapy for patients with unresectable stage III non-small cell lung cancer without disease progression after either concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (sCRT), according to findings presented today at the IASLC World Conference on Lung Cancer 2022 in Vienna.
Sugemalimab is a full-length, fully human IgG4 monoclonal antibody targeting PD-L1. GEMSTONE-301 is an ongoing phase 3 trial to evaluate sugemalimab as a consolidation treatment in patients with unresectable stage III non-small cell lung cancer without disease progression following chemoradiotherapy. The trial is the first phase 3 study in this setting to include patients who received either concurrent or sequential chemoradiotherapy. Previously, in the pre-planned progression-free survival interim analysis, sugemalimab showed a statistically significant and clinically meaningful improvement in progression-free survival compared with placebo (Lancet Oncol. 2022 Feb;23(2):209-219).
To follow up on this previous work, Yi-Long Wu, M.D., from Guangdong Provincial People's Hospital, in Guangzhou, China and colleagues finished a pre-planned progression-free survival final analysis.
Patients were stratified by ECOG PS (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 (BICR). 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 PFS final analysis (1 Mar 2022), 62 (24.3%) patients in the sugemalimab group and 26 (20.6%) patients in the placebo group are ongoing. The median follow-up duration was 27.1 and 23.5 months, respectively.
The median progression-free survival assessed by BICR was 10.5 in the sugemalimab group vs 6.2 months in the placebo group (stratified HR 0.65; 95% CI 0.50-0.84). The 24- and 36-month PFS 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, mPFS 8.1 vs 4.1 months) and cCRT (HR 0.71, mPFS 15.7 vs 8.3 months). Median overall survival was not reached with sugemalimab vs 25.9 months with placebo (HR 0.69; 95% CI 0.49-0.97), sCRT (HR 0.60, mOS NR vs 24.1 months) and cCRT (HR 0.75, mOS NR vs 32.4 months). The 24- and 36-month OS 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 or placebo, respectively.
Sustained PFS benefits and well-tolerated safety profile were observed in this progression-free survival final analysis, preliminary overall survival data showed a trend for benefit favoring sugemalimab. 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."
Dr. Yi-Long Wu, M.D., Guangdong Provincial People's Hospital, in Guangzhou, China
International Association for the Study of Lung Cancer