A protocol pre-specified interim overall survival (OS) analysis of GEMSTONE-302: A phase 3 study of sugemalimab (suge) versus placebo plus platinum-based chemotherapy (chemo) as first-line (1L) treatment for patients (pts) with metastatic non–small cell lung cancer (NSCLC).
Authors: Zhou Caicun , Wang Ziping , Sun Meili , Cao Lejie , Ma Zhiyong , Wu Rong , Yu Yan , Yao Wenxiu , Sun Si , Chen Jianhua , Zhuang Wu , Cui Jiuwei , Chen Xueqin , Lu You , Hu Chunhong , Wang Jingru , Chen Rumei , Qin Mengmeng , Wang Hao , Yang Jason 
Published: June 2022

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Background: GEMSTONE-302, a randomized, double-blind, phase 3 study, previously met its primary endpoint and demonstrated statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with suge+chemo vs placebo+chemo as a 1L treatment in pts with metastatic NSCLC. PFS benefit was observed in both squamous (sq) and non-squamous (nsq) NSCLC, regardless of PD-L1 expression levels. Here we report the data from a protocol pre-specified interim OS analysis. Methods: Pts with systemic treatment-naïve stage IV NSCLC, measurable disease per RECIST v1.1, ECOG PS 0-1, and no known EGFR, ALK, ROS1 and RET alterations were randomized 2:1 to receive suge (1200 mg, IV) or placebo plus chemo (sq-NSCLC: carboplatin+paclitaxel; nsq-NSCLC: carboplatin+pemetrexed) every 3 weeks for up to 4 cycles, followed by maintenance therapy (sq-NSCLC: suge/placebo; nsq-NSCLC: suge/placebo+pemetrexed) for up to 35 cycles. The primary endpoint was investigator assessed PFS (INV-PFS). Key secondary endpoints included OS, INV-PFS in pts with tumor PD-L1 expression ≥1%, and ORR. Pts in the placebo group could cross over to receive suge monotherapy upon disease progression. Results: As of 22 Nov 2021, among all 479 enrolled pts, 51 (15.9%) and 7 (4.4%), respectively, remained on treatment with suge+chemo or placebo+chemo. The median follow-up was 25.4 and 24.9 months, respectively. Following treatment discontinuation, 17.8% and 43.4% of the pts, respectively, received cross-over suge or other non-study anti-PD-(L)1-containing therapies. Median OS was 25.4 months in suge+chemo group vs 16.9 months in placebo+chemo group (HR = 0.65 [95%CI, 0.50-0.84], p = 0.0008), and 2-year OS rate was 51.7% vs 35.6%. OS benefits were observed across all subgroups including different tumor histologies (sq: HR = 0.56; nsq: HR = 0.72) and PD-L1 expression levels (≥1%: HR = 0.64; < 1%: HR = 0.66). In the intent-to-treat population, median PFS was 9.0 months with suge+chemo vs 4.9 months with placebo+chemo (HR = 0.49 [0.40-0.61]), and 2-year PFS rate was 20.8% vs 7.3%. In pts with PD-L1≥1%, the median PFS was 10.9 vs 4.9 months (HR = 0.48 [0.36-0.63], p < 0.0001). ORR was 63.4% vs 40.3% (p < 0.0001). Among pts with baseline brain metastases, suge+chemo improved their OS (HR = 0.45) and intracranial INV-PFS (post-hoc analysis, HR = 0.33) vs placebo+chemo. Safety profile was consistent with previously reported results. Conclusions: Suge plus chemo demonstrated statistically significant and clinically meaningful OS improvement compared with placebo plus chemo, irrespective of tumor histology or PD-L1 expression levels, in pts with newly diagnosed metastatic NSCLC, offering a new 1L treatment option for this group of pts. Clinical trial information: NCT03789604.