Background: PF-08634404 is a fully human IgG4 bispecific antibody that simultaneously targets PD-1 and VEGF. Phase 2 studies have shown promising efficacy and manageable safety with PF-08634404 as a monotherapy and with chemotherapy in first-line NSCLC. This study will evaluate the outcomes of PF-08634404 in combination with chemotherapy in ES-SCLC.
Trial design: Symbiotic-Lung-04 is a phase 2/3 trial (NCT07226999) in adult patients with histologically confirmed ES-SCLC who have not received prior systemic therapy. Patients must have measurable disease per RECIST 1.1, ECOG performance status of 0 or 1, and life expectancy ≥3 months. Patients with active CNS lesions or leptomeningeal disease are excluded. Patients may receive 1 cycle of chemotherapy without immune checkpoint inhibitors before enrollment for the management of life-threatening ES-SCLC.
The phase 2 portion is an open-label, multicenter, dose expansion study to confirm the recommended phase 3 dose (RP3D) and evaluate safety, tolerability, and preliminary efficacy of PF-08634404 plus chemotherapy. Approximately 40 patients will receive PF-08634404 plus carboplatin and etoposide for 4 cycles followed by PF-08634404 monotherapy. Primary endpoints are confirmed objective response rate (ORR) by investigator assessment per RECIST 1.1 and safety. Secondary endpoints include duration of response (DOR) and progression-free survival (PFS) by investigator, overall survival (OS), and dose-limiting toxicities. Phase 2 enrollment has begun.
The phase 3 portion is a double-blind, randomized study to evaluate the efficacy and safety of PF-08634404 plus chemotherapy versus anti–PD-L1 plus chemotherapy. Approximately 500 patients will be randomized 1:1 to receive PF-08634404 at RP3D or anti–PD-L1 plus carboplatin and etoposide for 4 cycles followed by maintenance therapy with PF-08634404 or anti–PD-L1. The primary endpoint is OS. Secondary endpoints include PFS, confirmed ORR, and DOR by blinded independent central review and safety.
Previously presented at ELCC 2026, FPN: 440TiP, Federico Cappuzzo et al. - Reused with permission