Background: PF-08634404, a fully human immunoglobulin G4 bispecific antibody simultaneously targeting PD-1 and VEGF, have shown promising efficacy and manageable safety with PF-08634404 10 mg/kg Q3W as monotherapy (confirmed objective response rate [cORR] of 67.6%) and with platinum-based chemotherapy (cORR of 75.0% in squamous and 58.6% in non-squamous) in first-line non-small cell lung cancer (NSCLC) in phase 2 studies.
Trial design: Symbiotic-Lung-01 is a global, double-blind, randomized phase 3 trial (NCT07222566) in adults with previously untreated, pathologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC regardless of PD-L1 expression. Patients must have measurable disease per RECIST 1.1, ECOG performance status of 0 or 1, and life expectancy of ≥3 months. Patients with known active brain metastases, active hepatitis B, 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, approximately 640 patients 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, approximately 770 patients 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.