GEMSTONE-301 PHASE III: Sugemalimab vs. Placebo in Chemoradiotherapy Patients

Patients with unresectable stage III non-small-cell lung cancer (NSCLC) often undergo sequential chemoradiotherapy as they have no access to or tolerance towards concurrent chemoradiotherapy. In this study, the safety and efficacy of the anti-PD-L1 antibody sugemalimab were evaluated in patients with stage III NSCLC whose disease had not progressed despite prior treatment with either concurrent or sequential chemoradiation.
The GEMSTONE-301 study is conducted at 50 hospitals and academic research centers in China on patients with locally advanced, unresectable, stage III NSCLC. Patients were eligible if they were 18 years or older, had an 0 or 1 performance status as per the Eastern Cooperative Oncology Group, and had not progressed after receiving either concurrent or sequential chemoradiotherapy. Patients were assigned to receive either sugemalimab 1,200 mg or a matching placebo intravenously every 3 weeks for up to 24 months in a 2:1 ratio utilizing an interactive voice-web response system.

Eastern Cooperative Oncology Group (ECOG) performance status, prior chemoradiotherapy, and total radiotherapy dose were used as stratification criteria. Treatment allocation was concealed from the researchers, trial coordinators, patients, and study sponsors. Progression-free survival in the full study population, as determined by blinded independent central review (BICR), was the primary endpoint. All trial participants who took at least one dose of their prescribed medication were evaluated for safety. After completing enrollment, the study’s primary endpoint was analyzed as intended, and the results are presented here.

Researchers assessed 564 patients between August 30, 2018, and December 31, 2020, and found that 381 were good candidates. All 255 sugemalimab-treated patients and 126 placebo-treated individuals completed the study’s treatment protocol. Those who received sugemalimab had a median follow-up of 14 months (IQR 6 months to 19 months), while those who received a placebo had a median follow-up of 13 months (IQR 7 months to 18 months). BICR assessed PFS was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs. 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Treatment-related adverse events were experienced by 22 (9%) of 255 patients in the sugemalimab group and 7 (6%) of 126 patients in the placebo group, with pneumonitis or immune-mediated pneumonitis being the most common (seven [3%] of 255 patients in the sugemalimab group and one [<1%] of 126 in the placebo group). Thirty-eight patients in the sugemalimab group (15%) and twelve in the placebo group (10%) experienced significant side events related to treatment. Two patients in the sugemalimab group and one patient in the placebo group died from pneumonia, one from pneumonia with immune-mediated pneumonitis, and one from acute liver failure.

Patients with stage III NSCLC whose illness has not progressed after sequential or concurrent chemoradiotherapy may benefit from sugemalimab as consolidation therapy. This conclusion has to be confirmed by longer-term studies.

Source: https://pubmed.ncbi.nlm.nih.gov/35038429/

Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03728556

Zhou, Q., Chen, M., Jiang, O., Pan, Y., Hu, D., Lin, Q., Wu, G., Cui, J., Chang, J., Cheng, Y., Huang, C., Liu, A., Yang, N., Gong, Y., Zhu, C., Ma, Z., Fang, J., Chen, G., Zhao, J., & Shi, A. (2022). Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. The Lancet Oncology, 23(2), 209–219. https://doi.org/10.1016/s1470-2045(21)00630-6

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