Abstract
BACKGROUND: In China, platinum-based doublet chemotherapy is the standard treatment for patients who have unresectable stage III non-small cell lung cancer (NSCLC), administered with radiotherapy on either a concurrent or sequential basis. However, NSCLC patients who undergo this treatment can expect poor median progression-free survival (PFS) of around 8-10 months and a dismal 5-year overall survival (OS) rate of about 15%. In the recent PACIFIC trial, durvalumab was demonstrated to hold significant clinical benefit for patients with locally advanced/unresectable NSCLC who experienced no disease progression after definitive concurrent chemoradiotherapy (cCRT). CS1001 is the first full-length, fully human immunoglobin G4 (IgG4) monoclonal antibody (mAb) that targets programmed death ligand-1 (PD-L1) created through the OMT transgenic rat platform. The phase Ia/Ib study indicated CS1001 was well tolerated and exhibited anti-tumor potential with a range of tumors. GEMSTONE-301 is a phase III randomized, double-blind, study to explore the efficacy and safety of CS1001 compared with a placebo as consolidation therapy for stage III unresectable NSCLC patients. METHODS: In this trial, eligible patients will be randomized to receive CS1001 1,200 mg or placebo, every 3 weeks (Q3W). The primary endpoint will be investigator-assessed PFS, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints will include OS, PFS assessment based on Blinded Independent Center Review (BICR), objective response rate (ORR), other efficacy measurements, safety, and tolerability. DISCUSSION: This phase III trial will determine the efficacy and safety of CS1001 as consolidation therapy in patients with locally advanced/unresectable (stage III) NSCLC who did not have disease progression after prior concurrent/sequential chemoradiotherapy (cCRT or sCRT), and is the first phase III trial on an anti-PD-L1 mAb initiated in China for this indication. PROTOCOL VERSION: Version 3.0/September 12, 2019.