A Study to Learn if a Combination of Fianlimab and Cemiplimab Versus Cemiplimab Alone is More Effective for Adult Participants With Advanced Non-Small Cell Lung Cancer (NSCLC)

Launched by REGENERON PHARMACEUTICALS · Mar 14, 2023

Keywords

ClinConnect Summary

This clinical trial is studying whether a new combination of two medications, fianlimab and cemiplimab, is more effective for treating advanced non-small cell lung cancer (NSCLC) than cemiplimab alone. The goal is to understand how well these treatments work together and to learn about any side effects they might cause. Researchers will also look at how these medications affect the quality of life for patients and how much of the drug stays in the bloodstream over time.

To be eligible for this study, participants must be adults with advanced NSCLC who have not received any prior systemic treatment for their cancer. They should have specific types of tumors and measurable lesions that doctors can see on scans. Additionally, the study will only include patients with certain characteristics, like having a good level of organ function and specific PD-L1 levels in their tumors. Participants can expect regular check-ups and monitoring during the trial to assess their health and response to the treatment. Overall, this study aims to provide valuable information that could improve treatment options for patients with advanced lung cancer.

Gender

ALL

Eligibility criteria

• Key Inclusion Criteria:
• • 1. 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.
• • 2. 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
• • 3. 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.
• • 4. 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.
• • 5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• • 6. Adequate organ and bone marrow function, as described in the protocol.
• Key Exclusion Criteria:
• • 1. Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime.
• • 2. 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.
• • 3. 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.
• • 4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.
• • 5. 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.
• • 6. 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).
• • 7. 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.
• • 8. 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.
• 9. 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 ≤1 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.
• • Note: Other protocol-defined Inclusion/ Exclusion Criteria apply.