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)
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 aim of the study is to see how effective the combination of fianlimab and cemiplimab is in treating advanced NSCLC, in comparison with cemiplimab by itself.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drugs
* How much study drug is in your blood at different times
* Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)
* How administering the study drugs might improve your quality of life
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
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.
Primary outcome measure(s)
Objective response rate (ORR) as assessed by blinded independent central review (BICR), using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) — Up to 136 weeks Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)
Trial sites (106)
Facility
City
Region
Status
Arizona Clinical Research Center
Tucson
Arizona
Yuma Regional Medical Center
Yuma
Arizona
Emad Ibrahim, MD, Inc.
Redlands
California
Eastern CT Hematology and Oncology Associates
Norwich
Connecticut
Clermont Oncology Center
Clermont
Florida
Miami Veterans Administration HealthCare System
Miami
Florida
Mid Florida Hematology and Oncology Center
Orange City
Florida
Pinellas Hematology and Oncology
St. Petersburg
Florida
Tallahassee Memorial Healthcare
Tallahassee
Florida
Moffitt Cancer Center
Tampa
Florida
University of Illinois
Chicago
Illinois
Mary Bird Perkins Cancer Center
Baton Rouge
Louisiana
Hattiesburg Clinic
Hattiesburg
Mississippi
Mercy South
St Louis
Missouri
St. Vincent Healthcare
Billings
Montana
New Mexico Cancer Care Alliance
Albuquerque
New Mexico
Clinical Research Alliance Inc
Westbury
New York
Gabrail Cancer Center Research
Canton
Ohio
University of Tennessee Medical Center
Knoxville
Tennessee
Renovatio Clinical
El Paso
Texas
MD Anderson Cancer Center
Houston
Texas
University of Virginia Medical Center
Charlottesville
Virginia
Bon Secours Cancer Institute Richmond
Midlothian
Virginia
Macquarie University Health Science Center (MQ Health)
Macquarie Park
New South Wales
Riverina Cancer Care Centre (RCCC)
Wagga Wagga
New South Wales
Southern Medical Day Care Centre
Wollongong
New South Wales
Ballarat Regional Integrated Cancer Centre (BRICC)
Ballarat
Victoria
Bendigo Hospital
Bendigo
Victoria
British Columbia Cancer Center-Kelowna
Kelowna
British Columbia
Cancer Center of Adjara
Batumi
Adjara
Israeli Georgian Medical Research Clinic Helsicore
Tbilisi
Georgia
Research Institute of Clinical Medicine
Tbilisi
Georgia
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
Tbilisi
Georgia
NNLE New Vision University Hospital
Tbilisi
Georgia
The Institute of Clinical Oncology
Tbilisi
Georgia
TIM - Tbilisi Institute of Medicine
Tbilisi
Georgia
JSC Evex Hospitals - Caraps Medline
Tbilisi
Georgia
Soroka University Medical Center
Beersheba
Southern District
Shaare Zedek Medical Center
Jerusalem
Israel
Tel Aviv Sourasky Medical Center
Tel Aviv
Israel
+ 66 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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