A phase 2/3 study of fianlimab, cemiplimab, plus chemotherapy versus cemiplimab plus chemotherapy in first-line treatment of advanced non-small cell lung cancer.

person Nashat Gabrail Gabrail Cancer and Research Center, Canton, OH info_outline Nashat Gabrail, Miranda Gogishvili, Tamta Makharadze, Nana Chikhladze, Neil E. Faulkner, Santosh Nair, Emad Ibrahim, Daniel Brungs, Luke Dreisbach, Gopal Kunta, Solange Peters, Christopher Nguyen, Maria Ghattas, Siyu Li, Mark Salvati, Israel Lowy, Matthew G. Fury, Luca Paoluzzi, Tamar Melkadze

Authors person Nashat Gabrail Gabrail Cancer and Research Center, Canton, OH info_outline Nashat Gabrail, Miranda Gogishvili, Tamta Makharadze, Nana Chikhladze, Neil E. Faulkner, Santosh Nair, Emad Ibrahim, Daniel Brungs, Luke Dreisbach, Gopal Kunta, Solange Peters, Christopher Nguyen, Maria Ghattas, Siyu Li, Mark Salvati, Israel Lowy, Matthew G. Fury, Luca Paoluzzi, Tamar Melkadze Organizations Gabrail Cancer and Research Center, Canton, OH, High Technology Medical Center, University Clinic Ltd., Tbilisi, Georgia, LTD High Technology Hospital Med Center, Batumi, Georgia, JSC Vian Caraps Medline, European University, Tbilisi, Georgia, University of Tennessee Medical Center, Knoxville, TN, Mid Florida Cancer Centers, Orange City, FL, Emad Ibrahim, MD, Inc., Redlands, CA, Southern Medical Day Care Center, Wollongong, NSW, Australia, Desert Hematology Oncology Medical Group, Inc., Rancho Mirage, CA, Clermont Oncology Center, Clermont, FL, University Hospital CHUV, Lausanne, Switzerland, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, Todua Clinic, Tbilisi, Georgia Abstract Disclosures Research Funding Regeneron Pharmaceuticals, Inc. Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Anti–programmed cell death-1 (PD-1) therapies have improved outcomes in patients with NSCLC; however, most patients do not respond or only respond for a limited time. The combination of cemiplimab (anti–PD-1) and chemotherapy has been studied for the first-line treatment of advanced NSCLC (aNSCLC), regardless of programmed cell death-ligand 1 (PD-L1) status. While the standard of care continues to evolve for NSCLC, one approach to potentially improve outcomes is the combination of checkpoint inhibitors (IO) with chemotherapy. Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab are both high-affinity, fully human IgG4 monoclonal antibody IO therapies that have shown promising clinical activity when combined in patients with aNSCLC in a Phase 1 study (NCT03005782). This ongoing study will further investigate the combination of fianlimab + cemiplimab + chemotherapy. Methods: This is a randomized, multicenter, Phase 2/3 study of fianlimab + cemiplimab + platinum-doublet chemotherapy (chemo) versus cemiplimab + chemo in patients with unresectable stage IIIB/IIIC or stage IV NSCLC irrespective of PD-L1 expression levels (NCT05800015). This study will be conducted globally at approximately 210 sites. Patient eligibility criteria: ≥18 years old; squamous or non-squamous histology with stage IIIB, IIIC, or IV disease; valid PD-L1 result; ≥1 radiographically measurable lesion by computed tomography/magnetic resonance imaging; Eastern Cooperative Oncology Group performance status ≤1; adequate organ and bone marrow function. The Phase 2 portion will be used to determine the fianlimab dose selected for the Phase 3 portion: patients will be randomized 1:1:1 to receive fianlimab high dose + cemiplimab 350 mg + chemo (Arm A), fianlimab low dose + cemiplimab 350 mg + chemo (Arm B), or cemiplimab 350 mg + chemo + placebo (Arm C), Q3W IV. In Phase 3, patients will be randomized 1:1 into one of two treatment arms (either Arm A or Arm B, and Arm C) based on findings from Phase 2. The primary endpoint of Phase 2 is objective response rate (ORR) per blinded independent central review. The primary endpoint of Phase 3 is overall survival. The secondary endpoints include efficacy (ORR, disease control rate, time to tumor response, duration of response, progression-free survival, and overall survival), safety and tolerability, immunogenicity (anti-drug antibodies and neutralizing antibodies against fianlimab or cemiplimab in serum), patient-reported outcomes, and pharmacokinetics. This study and a parallel study of fianlimab + cemiplimab in patients with aNSCLC with tumors expressing PD-L1 ≥50% (NCT05785767) are currently open for enrollment. Clinical trial information: NCT05800015.

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