The addition of CS1001, a monoclonal antibody against PD-L1, to platinum-based chemotherapy significantly prolonged progression-free survival (PFS) over chemotherapy in treatment-naive patients with advanced non-small cell lung cancer (NSCLC), according to phase III findings presented at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.
Caicun Zhou of the Department of Oncology, Shanghai Pulmonary Hospital in Shanghai, China presented findings on behalf of fellow investigators from a pre-planned analysis of PFS data from the randomised, double-blind, phase III GEMSTONE-302 (NCT03789604) 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 anti-tumour activity across a range of cancers, including NSCLC.
Patients with advanced NSCLC who had received no previous systemic therapy for metastatic disease, were stratified by histology (squamous versus non-squamous), PD-L1 expression levels (≥1% versus <1%), and ECOG performance status (0 versus 1).
Following 2:1 randomisation, 320 patients received CS1001 by i.v. at 1200 mg every 3 weeks and 159 patients received placebo; both groups also were treated with platinum-based chemotherapy for up to 4 cycles, followed by a maximum 2 years of maintenance with either CS1001 or placebo. Pemetrexed was also given as maintenance therapy to patients with non-squamous NSCLC.
Investigator-assessed PFS by RECIST v1.1 served as the primary endpoint.
The addition of CS1001 to chemotherapy significantly increased patient benefit
Baseline characteristics were balanced between the two treatment arms.
As of 8 June 2020, the median follow-up was 8.67 and 8.34 months in the CS1001 and placebo arms, respectively.
A significant PFS improvement was observed with CS1001 plus chemotherapy over placebo/chemotherapy; the median PFS was 7.8 versus 4.9 months (stratified hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.39-0.64; p < 0.0001).
The objective response rate (ORR) was 61.4% with CS1001/chemotherapy compared to 39.2% with placebo/chemotherapy.
Although overall survival (OS) data were immature, a trend towards prolonged OS was observed with the respective treatments, where median OS was not reached versus 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 versus non-squamous histology and PD-L1 expression levels.
Both treatments showed similar safety profiles, with the exception of the occurrence of immune-related adverse events (AEs) in the CS1001/chemotherapy arm that were mostly grades 1 and 2. Grade ≥3 AEs 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 pointed out it 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 non-squamous NSCLC.
These findings demonstrated that CS1001 combined with chemotherapy provided a statistically significant and clinically meaningful PFS benefit together with a well-tolerated safety profile compared to chemotherapy across subgroups with different histology and PD-L1 expression levels.
The authors predicted that CS1001 plus chemotherapy will potentially become a new standard of care for the first-line treatment of advanced NSCLC after receiving regulatory approval.
Funding for this study was reported from CStone Pharmaceuticals.
LBA4 – Zhou C, Wang Z, Sun Y, et al. GEMSTONE-302: A phase III study of platinum-based chemotherapy (chemo) with placebo or CS1001, an anti-PD-L1 antibody, for first-line (1L) advanced non-small cell lung cancer (NSCLC). ESMO Asia Virtual Congress 2020 (20-22 November).