151TiP Phase III trial ResQ201A of NAI plus tislelizumab and docetaxel vs. docetaxel monotherapy for advanced or metastatic NSCLC resistant to ICI therapy

Background: PF-08634404 is a fully human immunoglobulin G4 bispecific antibody that simultaneously targets PD-1 and VEGF.Phase II studies have shown promising efficacy and manageable safety with PF-08634404 as monotherapy and with chemotherapy in 1L non-small cell lung cancer (NSCLC).This study will evaluate PF-08634404 in combination with different anticancer agents in advanced solid tumors including NSCLC.Trial design: Symbiotic-Lung-20 is an open-label, multicenter, phase Ib/II study (NCT07227298) in adults with advanced solid tumors.In parts A and B, PF-08634404 is combined with different vedotin-based antibody-drug conjugates (ADCs; sigvotatug vedotin and PDL1V) in patients (pts) with pathologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC who have not received prior systemic therapy in 1L.Pts must have ECOG performance status 0 or 1 and life expectancy 3 months.Pts with actionable genetic alterations or known active CNS lesions are excluded.Future cohorts may investigate other PF-08634404 combinations and tumor types.The phase Ib safety run-in portion will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in parts A and B to determine up to 2 recommended combination doses for phase II with each ADC.Approximately 42 pts will be enrolled with 3 pts/dose level.Primary endpoints are adverse events (AEs) and dose-limiting toxicities.Key secondary endpoints include confirmed objective response rate (cORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) all by investigator, and overall survival (OS).The phase II dose optimization and expansion portions will evaluate the recommended combination doses from phase Ib.Approximately 40 pts each in parts A and B will be randomized 1:1 to receive the recommended combination doses for each regimen in dose optimization.Upon selection of the recommended dose for expansion, 20 additional pts will be enrolled in each part.Primary endpoints are cORR by investigator and AEs.Key secondary endpoints include DCR, DOR, and PFS all by investigator, and OS.Enrollment has begun.