148TiP A phase III trial of a PD-1/VEGF bispecific antibody (PF-08634404) vs pembrolizumab in combination with platinum-based chemotherapy in first-line for locally advanced or metastatic non-small cell lung cancer (Symbiotic-Lung-01)

Background: PF-08634404 is a fully human immunoglobulin G4 PD-1/VEGF bispecific antibody.Phase II studies have shown promising efficacy and manageable safety with PF-08634404 as monotherapy and with platinum-based chemotherapy in first-line non-small cell lung cancer (NSCLC), providing rationale for further evaluation of PF-08634404 plus platinum-based chemotherapy in patients (pts) with advanced NSCLC compared to standard of care in a phase III study.Trial design: Symbiotic-Lung-01 is a global, double-blind, randomized phase III trial (NCT07222566) in adults with previously untreated, pathologically confirmed unresectable locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC regardless of PD-L1 expression.Pts must have measurable disease per RECIST 1.1, ECOG performance status of 0 or 1, and life expectancy of 3 months.Pts with known active brain metastases or whose tumors have actionable genomic alterations with approved first-line therapies are excluded.The study has 2 parallel parts based on tumor histology.In part 1, 640 pts with squamous NSCLC will be randomized 1:1 to receive either PF-08634404 or pembrolizumab intravenously plus carboplatin and investigator's choice of paclitaxel or nab-paclitaxel for 4 cycles followed by maintenance therapy with PF-08634404 or pembrolizumab for up to 35 cycles.In part 2, 770 pts with nonsquamous NSCLC will be randomized 1:1 to receive either PF-08634404 or pembrolizumab plus carboplatin and pemetrexed for 4 cycles followed by maintenance therapy with PF-08634404 or pembrolizumab plus pemetrexed for up to 35 cycles, after which pemetrexed may continue.Randomization is stratified by PD-L1 expression, brain metastases, and region.Dual primary endpoints are overall survival and progression-free survival by blinded independent central review (BICR) per RECIST 1.1.The key secondary endpoint is confirmed objective response rate by BICR.Other secondary endpoints include additional measures of efficacy, safety, quality of life, pharmacokinetics, and biomarkers.All endpoints will be assessed in each part.Enrollment has begun.Clinical trial identification: NCT07222566.