Sugemalimab (formerly CS1001) is a fully human immunoglobulin G4 (IgG4, s228p) monoclonal antibody that targets PD-L1.1 GEMSTONE-302, a randomized, double-blind, phase 3 study, met its primary end point and demonstrated statistically significant and clinically meaningful improvement of progression-free survival (PFS) with sugemalimab plus chemotherapy compared with placebo plus platinum-based chemotherapy as a first-line option in patients with metastatic non–small-cell lung cancer (NSCLC). In addition, the combination regimen improved PFS in both squamous and nonsquamous NSCLC, regardless of PD-L1 expression levels.2
Zhou and colleagues reported the interim overall survival (OS) analysis results that were prespecified by the study protocol..2 The trial included patients with systemic treatment-naïve stage IV NSCLC, measurable disease per RECIST version 1.1, Eastern Cooperative Oncology Group performance status of 0-1, and no known EGFR, ALK, ROS1, and RET alterations. Patients were randomized 2:1 to receive sugemalimab (1200 mg, intravenous) or placebo plus platinum-based chemotherapy every 3 weeks for up to 4 cycles, followed by up to 35 cycles of maintenance therapy, which included sugemalimab or placebo for patients with squamous histology and sugemalimab or placebo plus pemetrexed for patients with nonsquamous histology.2
The primary end point was investigator-assessed PFS, and key secondary end points included OS, PFS in patients with tumor PD-L1 expression ≥1%, and overall response rate (ORR). In addition, patients in the placebo group could cross over to receive sugemalimab monotherapy upon disease progression.2
As of November 22, 2021, among all 479 enrolled patients, 51 (15.9%) and 7 (4.4%), respectively, remained on treatment with sugemalimab plus chemotherapy or placebo plus chemotherapy. The median follow-up was 25.4 months and 24.9 months, respectively. Following treatment discontinuation, 17.8% and 43.4% of the patients, respectively, received crossover sugemalimab or other nonstudy anti–PD-(L)1-containing therapies.2
In the intent-to-treat population, median PFS was 9.0 months with sugemalimab plus chemotherapy compared with 4.9 months with placebo plus chemotherapy (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.40-0.61), and the 2-year PFS rate was 20.8% versus 7.3%, respectively. In patients with PD-L1 ≥1%, the median PFS was 10.9 versus 4.9 months (HR, 0.48, 95% CI, 0.36-0.63; P <.0001). ORR was 63.4% versus 40.3% (P <.0001). In addition, sugemalimab plus chemotherapy resulted in clinical benefit in patients with baseline brain metastases and improved their OS (HR, 0.45) and intracranial PFS (post-hoc analysis, HR, 0.33) compared with placebo plus chemotherapy. No new safety signals were observed.2
Median OS was 25.4 months in the sugemalimab plus chemotherapy group compared with 16.9 months in the placebo plus chemotherapy group (HR, 0.65; 95% CI, 0.50-0.84; P = .0008), and the 2-year OS rate was 51.7% versus 35.6%, respectively. All subgroups treated with the sugemalimab-based regimen achieved OS benefit, including different tumor histologies (squamous: HR, 0.56; nonsquamous: HR, 0.72) and with varying PD-L1 expression levels (≥1%: HR, 0.64; <1%: HR, 0.66).
The researchers concluded that sugemalimab plus chemotherapy demonstrated statistically significant and clinically meaningful PFS and OS improvement compared with placebo plus chemotherapy, irrespective of tumor histology or PD-L1 expression levels, in patients with newly diagnosed metastatic NSCLC, thus offering a new first-line treatment option in this setting.
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