A phase 2/3 study of fianlimab plus cemiplimab versus cemiplimab in patients with advanced non-small cell lung cancer with tumors expressing PD-L1 ≥50%.
Authors: Faulkner Neil E. , Melkadze Tamar , Nair Santosh , Gabrail Nashat , Kunta Gopal , Ibrahim Emad , Dreisbach Luke , Brungs Daniel , Chikhladze Nana , Gogishvili Miranda , Vokes Natalie I , Hiley Tara , Nguyen Christopher , Ghattas Maria , Li Siyu , Salvati Mark , Lowy Israel , Fury Matthew G. , Paoluzzi Luca 
Published: June 2024

TPS8663 Background: Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti–programmed cell death-1 [PD-1]) are high-affinity, fully human, IgG4 monoclonal antibodies. In patients (pts) with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50% with no actionable mutations, first-line cemiplimab monotherapy showed significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy, with a safety profile consistent with previous reports for cemiplimab monotherapy. Despite pts’ selection by PD-L1 expression, only ~50% of pts respond to PD-1 therapy, thus there is a need for immune-oncology combinations like anti–LAG-3 plus anti–PD-1 to potentially improve outcomes. Methods: This is a randomized, double-blind, Phase 2/3 study (NCT05785767) to evaluate fianlimab + cemiplimab versus cemiplimab monotherapy as first-line treatment in pts with aNSCLC and tumors expressing PD-L1 ≥50%. The study will be conducted globally at ~210 sites. Key inclusion criteria: ≥18 years old; histologically confirmed squamous or non-squamous stage IIIB/C (not candidates for surgical resection or definitive chemoradiation) or stage IV NSCLC (no prior systemic treatment for recurrent or metastatic NSCLC); PD-L1 expression in ≥50% of tumor cells; ≥1 radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1; Eastern Cooperative Oncology Group performance status ≤1; adequate organ and bone marrow function. This study has Phase 2 and Phase 3 parts and is expected to enroll ~850 pts. Pts will be treated for up to 108 weeks. In Phase 2, 150 patients will be randomized 1:1:1 into three treatment arms (Q3W IV): Arm A, fianlimab high dose + cemiplimab 350 mg; Arm B, fianlimab low dose + cemiplimab 350 mg; Arm C, cemiplimab 350 mg + saline/dextrose placebo. Based on findings from Phase 2, the dose of fianlimab (low or high) will be selected for Phase 3. In Phase 3, 700 patients will be randomized 1:1 into either experimental Arm A or B, and comparator Arm C (cemiplimab + placebo). In Phase 2, the primary endpoint is objective response rate (ORR) per blinded independent central review (BICR). The secondary endpoints are safety, ORR per investigator assessment, disease control rate (DCR), time to tumor response (TTR), duration of response (DOR), PFS, OS, patient-reported outcomes, pharmacokinetics, and immunogenicity. In Phase 3, the primary endpoint is OS in patients receiving fianlimab + cemiplimab versus cemiplimab monotherapy. Secondary endpoints are safety, ORR, DCR, TTR, DOR, and PFS, per BICR and investigator assessment, patient-reported outcomes, pharmacokinetics, and immunogenicity. This study is open for enrollment along with a second study of fianlimab + cemiplimab + chemotherapy in aNSCLC. Clinical trial information: NCT05785767 .