The addition of CS1001, an anti–PD-L1 monoclonal antibody, to platinum-based chemotherapy significantly prolonged progression-free survival vs chemotherapy in treatment-naive patients with advanced non–small cell lung cancer (NSCLC), according to phase III findings presented by Zhou et al at the ESMO Asia Virtual Congress 2020 (Abstract LBA4).

Researchers presented findings from a preplanned analysis of progression-free survival data from the randomized, double-blind, phase III GEMSTONE-302 study comparing the efficacy and safety of first-line chemotherapy with and without CS1001 in advanced NSCLC.

CS1001 is a full-length, fully human IgG4 monoclonal antibody that targets PD-L1. Previous reports found that it was well tolerated and showed promising antitumor activity across a range of cancers, including NSCLC.

Trial Details

Patients with advanced NSCLC who had received no previous systemic therapy for metastatic disease were stratified by histology (squamous vs nonsquamous), PD-L1 expression levels (≥ 1% vs < 1%), and Eastern Cooperative Oncology Group performance status (0 vs 1).

Following 2:1 random assignment, 320 patients received intravenous CS1001 at 1,200 mg every 3 weeks and 159 patients received placebo; both groups also were treated with platinum-based chemotherapy for up to four cycles, followed by a maximum 2 years of maintenance with either CS1001 or placebo. Pemetrexed was also given as maintenance therapy to patients with nonsquamous NSCLC.

Baseline characteristics were balanced between the two treatment arms.

Investigator-assessed progression-free survival as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 was the primary endpoint.

Results

As of June 2020, the median follow-up was 8.67 and 8.34 months in the CS1001 and placebo arms, respectively.

A significant progression-free survival improvement was observed with CS1001 plus chemotherapy over placebo/chemotherapy; the median progression-free survival was 7.8 vs 4.9 months (stratified hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.39–0.64, P < .0001).

The objective response rate was 61.4% with CS1001/chemotherapy compared to 39.2% with placebo/chemotherapy. Although overall survival data were immature, a trend towards prolonged overall survival was observed with the respective treatments, where median overall survival was not reached vs 14.75 months (stratified HR = 0.66, 95% CI = 0.44–0.97).

Subgroup analyses demonstrated similar clinical benefit with the addition of CS1001 across squamous vs nonsquamous histology and PD-L1 expression levels.

Both treatments showed similar safety profiles, with the exception of the occurrence of immune-related adverse events in the CS1001/chemotherapy arm that were mostly grades 1 and 2. Grade ≥ 3 adverse events were reported in 61.9% of patients receiving CS1001 and 61.6% of patients receiving placebo. No new unexpected safety signals were found.

The authors noted that this was the first phase III study conducted in China for an anti–PD-L1 monoclonal antibody plus chemotherapy in treatment-naive patients with advanced squamous or nonsquamous NSCLC.

These findings demonstrated that CS1001 combined with chemotherapy provided a statistically significant and clinically meaningful progression-free survival benefit together with a well-tolerated safety profile compared to chemotherapy across subgroups with different histology and PD-L1 expression levels.

Disclosure: Funding for this study was reported from CStone Pharmaceuticals. For full disclosures of the study authors, visit oncologypro.esmo.org.