A randomized, double blinded, multicenter phase 3 study of platinum-based chemotherapy with or without QL1706 as adjuvant therapy in completely resected stage II-IIIb NSCLC.

Abstract

TPS8606 Background: Adjuvant atezolizumab is approved for PD-L1 positive stage II-IIIA NSCLC in USA and China. To date, there are few clinical studies on dual immune checkpoint inhibitors in adjuvant settings of NSCLC. QL1706, a MabPair product, is a novel bifunctional antibody containing a mixture of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 antibodies. QL1706 monotherapy has demonstrated good safety and promising antitumor activity in advanced solid tumors in a phase Ia/Ib study with 518 patients, including 146 NSCLC patients. Meanwhile, in NSCLC patients with negative oncogene drivers, QL1706 plus 2 cycles of chemotherapy as first line treatment resulted in an ORR of 58.6% (17/29) and the mPFS was 6.97 months. Furthermore, in the EGFR mutant NSCLC patients who previously were treated with EGFR-TKI, QL1706 plus platinum-based chemotherapy and bevacizumab showed promising efficacy with an ORR of 64.5% (20/31). This study is designed to investigate the efficacy and safety of QL1706 or placebo plus platinum doublet chemotherapy as adjuvant treatment in stage II-IIIB NSCLC. Methods: In this phase Ⅲ, randomized, double-blind, placebo-controlled, multicenter study, 632 eligible pts, who is completely resected stage Ⅱ-ⅢB NSCLC (AJCC 8th) with negative EGFR, ALK etc, will be enrolled. Pts will be randomized 1:1 to receive QL1706 (5 mg/kg) or placebo plus chemotherapy, administered every 3 weeks (Q3W). The regimen of vinorelbine/paclitaxel plus cisplatin/carboplatin is chosen for squamous NSCLC, while pemetrexed/vinorelbine plus cisplatin/carboplatin for non-squamous NSCLC. Randomization will be stratified by PD-L1 TPS (ie, < 1%, ≥1%), disease stage (stage II, III) and predominant tumor histology (ie, squamous vs non-squamous). The primary endpoint is disease-free survival (DFS) per investigators in PD-L1 TPS ≥1% pts and in all randomized pts, which will be tested hierarchically. An interim analysis is to occur when about 70% DFS events achieved in pts with PD-L1≥1%. Enrollment began in Nov, 2022. ClinicalTrials.gov NCT05487391. Clinical trial information: NCT05487391 .