Clinical Trial 23094

• Overview

  Study Title:

  A Randomized, Double-Blind Phase 2/3 Study of Fianlimab (Anti-LAG-3 antibody) in Combination with Cemiplimab (Anti-PD-1 antibody) versus Cemiplimab Monotherapy in First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with Tumors Expressing PD-L1 >=50%

  Summary:

  This study is researching an experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab (also called REGN2810), individually called a "study drug" or collectively called "study drugs". The study is focused on patients who have advanced non-small cell lung cancer (NSCLC). The purpose of this study is to see how effective the combination of fianlimab and cemiplimab is in treating advanced NSCLC, in comparison with cemiplimab by itself.

  Objective:

  Phase 2 Primary Objective * To assess the objective response rate (ORR) per blinded independent central review (BICR) of combination of cemiplimab and fianlimab at both 1600 mg and 400 mg compared with cemiplimab monotherapy in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors express programmed death cell ligand-1 (PD-L1) in ≥50% of tumor cells. Phase 2 Secondary Objective * To assess the safety and tolerability of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy. * To assess other anti-tumor activities of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy, as assessed by ORR by investigator assessment, disease control rate (DCR), time to tumor response (TTR), duration of response (DOR), progression free survival (PFS) by BICR and investigator assessment, and overall survival (OS). * To assess the patient-reported outcomes (via European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30], -Lung Cancer 13 [EORTC QLQ-LC13], and 5-Level EQ-5D Scale [EQ-5D-5L]) of combination of cemiplimab and fianlimab compared with cemiplimab monotherapy. * To assess patient-reported fatigue as measured by the fatigue severity and interference with usual or daily activities items of the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for combination of cemiplimab and fianlimab compared with cemiplimab monotherapy. * To characterize the pharmacokinetics (PK) of fianlimab and cemiplimab. *To assess the immunogenicity of fianlimab and cemiplimab. Phase 3 Primary Objective * To compare OS of cemiplimab and fianlimab versus cemiplimab monotherapy. Phase 3 Secondary Objectives * To assess the safety and tolerability of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy. * To assess other anti-tumor activities of combination of cemiplimab and fianlimab and cemiplimab monotherapy, as measured by ORR, DCR, TTR, DOR, and PFS, by BICR and investigator assessment. *To assess the patient-reported outcomes (via EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L) of combination of cemiplimab and fianlimab compared with cemiplimab monotherapy. * To assess patient-reported fatigue as measured by the fatigue severity and interference items of the PRO-CTCAE for combination of cemiplimab and fianlimab compared with cemiplimab. * To characterize the PK of fianlimab and cemiplimab. * To assess the immunogenicity of fianlimab and cemiplimab.

• Treatments

  Therapies:

  Immunotherapy

  Medications:

  Cemiplimab (); Fianlimab (); Placebo (); REGN2810 (Cemiplimab)

• Inclusion Criteria

  Inclusion Criteria:
  • Patients with non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic disease), who received no prior systemic treatment for recurrent or metastatic NSCLC.
  • Availability of an archival or on-study formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol
  • For enrollment in phase 2, patients should have PD-L1 levels ≥ 50%, as determined by a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) (or equivalently licensed, according to local regulations) accredited laboratory, as described in the protocol. For enrollment in phase 3, patients should have expression of programmed cell death ligand-1 (PD-L1) in ≥50% of tumor cells stained using an assay performed by a central laboratory, as described in the protocol.
  • At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ and bone marrow function, as described in the protocol.

• Exclusion Criteria

  Exclusion Criteria:
  • Patients who have never smoked, defined as smoking 100 or less cigarettes in a lifetime.
  • Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated, and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Patients must be off (immunosuppressive doses of) corticosteroid therapy.
  • Patients with tumors tested positive for actionable epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or c-ros oncogene 1 (ROS1) fusions, as described in the protocol.
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.
  • History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.
  • Known primary immunodeficiencies, either cellular (eg, DiGeorge syndrome, T-cell-negative severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies (eg, T- and B-cell negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency).
  • Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-mediated treatment-emergent adverse events (imTEAEs). Patients with uncontrolled type 1 diabetes mellitus or with uncontrolled adrenal insufficiency are excluded. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
  • Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization. Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Patients with clinically relevant systemic immune suppression within the last 3 months before trial enrollment are excluded. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
  • Patients who have received prior systemic therapies are excluded with the exception of the following: 1.) Adjuvant or neoadjuvant platinum-based doublet chemotherapy (after surgery and/or radiation therapy) if recurrent or metastatic disease develops more than 6 months after completing therapy as long as toxicities have resolved to CTCAE grade ≤1 or baseline with the exception of alopecia and peripheral neuropathy. 2.) Anti-PD-(L) 1 with or without LAG-3 as an adjuvant or neoadjuvant therapy as long as the last dose is >12 months prior to enrollment. 3.) Prior exposure to other immunomodulatory or vaccine therapies as an adjuvant or neoadjuvant therapy, Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibodies as long as the last dose is >6 months prior to enrollment. Immune-mediated AEs must be resolved to CTCAE grade 0 or1 or baseline by the time of enrollment. Endocrine immune-mediated AEs controlled with hormonal or other non-immunosuppressive therapies without resolution prior to enrollment are allowed.
  • Other criteria may apply.

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