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)

March 18, 2024 updated by: Regeneron Pharmaceuticals

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%

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

850

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia, 2109
      • Wollongong, New South Wales, Australia, NSW 2500
    • Victoria
      • Ballarat, Victoria, Australia, 3350
        • Recruiting
        • Ballarat Regional Integrated Cancer Centre (BRICC)
        • Contact:
      • Bendigo, Victoria, Australia, 3550
  • Georgia
      • Tbilisi, Georgia, 0112
        • Recruiting
        • Israeli Georgian medical research clinic Helsicore
        • Contact:
      • Tbilisi, Georgia, 0159
        • Recruiting
        • JSC K. Eristavi National Center of Experimental and Clinical Surgery
        • Contact:
      • Tbilisi, Georgia, 179
      • Tbilisi, Georgia, 112
        • Recruiting
        • Research Institute of Clinical Medicine
        • Contact:
      • Tbilisi, Georgia, 144
        • Recruiting
        • Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
        • Contact:
      • Tbilisi, Georgia, 159
      • Tbilisi, Georgia, 0160
        • Recruiting
        • TIM - Tbilisi Institute of Medicine
        • Contact:
    • Adjaria
      • Batumi, Adjaria, Georgia, 6000
  • Korea, Republic of
      • Daejeon, Korea, Republic of, 35015
        • Recruiting
        • Chungnam National University Hospital
        • Contact:
      • Incheon, Korea, Republic of, 21565
        • Recruiting
        • Gachon University Gil Medical Center
        • Contact:
      • Incheon, Korea, Republic of, 22332
        • Recruiting
        • Inha University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 8308
      • Ulsan, Korea, Republic of, 44033
        • Recruiting
        • Ulsan University Hospital
        • Contact:
    • Chungbuk
      • Cheongju-si, Chungbuk, Korea, Republic of, 28644
        • Recruiting
        • Chungbuk National University Hospital
        • Contact:
    • Gyeonggi
      • Suwon, Gyeonggi, Korea, Republic of, 16499
    • Jeollabuk-do
      • Jeonju, Jeollabuk-do, Korea, Republic of, 54907
        • Recruiting
        • Jeonbuk National University Hospital
        • Contact:
  • United States
    • Arizona
      • Yuma, Arizona, United States, 85364
    • California
      • Rancho Mirage, California, United States, 92270
        • Recruiting
        • Desert Hematology Oncology Medical Group, Inc.
        • Contact:
      • Redlands, California, United States, 92373
    • Florida
      • Clermont, Florida, United States, 34711
      • Miami, Florida, United States, 33125
        • Recruiting
        • Miami Veterans Administration HealthCare System
        • Contact:
      • Orange City, Florida, United States, 32763
        • Recruiting
        • Mid Florida Hematology and Oncology Center
        • Contact:
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Recruiting
        • Mary Bird Perkins Cancer Center
        • Contact:
    • Mississippi
    • New Jersey
    • New York
      • Port Jefferson Station, New York, United States, 11776
        • Recruiting
        • New York Cancer and Blood Specialists
        • Contact:
      • Westbury, New York, United States, 11590
    • Ohio
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee Medical Center
        • Contact:
      • Knoxville, Tennessee, United States, 37916-2300
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Medical Center
        • Contact:
      • Midlothian, Virginia, United States, 23114

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: fianlimab+cemiplimab
Phase 2: fianlimab (HD) Phase 3: fianlimab (chosen dose)
Drug: fianlimab
Every three weeks (Q3W) as intravenous (IV) co-infusion
Other Names:
  • REGN3767
Drug: cemiplimab
Q3W as IV co-infusion
Other Names:
  • REGN2810
  • Libtayo
Experimental: B: fianlimab+cemiplimab
Phase 2: fianlimab (LD) Phase 3: fianlimab (chosen dose)
Drug: fianlimab
Every three weeks (Q3W) as intravenous (IV) co-infusion
Other Names:
  • REGN3767
Drug: cemiplimab
Q3W as IV co-infusion
Other Names:
  • REGN2810
  • Libtayo
Experimental: C: cemiplimab monotherapy+placebo
Phase 2 and Phase 3
Drug: cemiplimab
Q3W as IV co-infusion
Other Names:
  • REGN2810
  • Libtayo
Drug: Placebo
Q3W as IV co-infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 5 years
Phase 3 The time from randomization to the date of death due to any cause
Up to 5 years
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)
Time Frame: Up to 136 weeks
Phase 2 Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)
Up to 136 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 A TEAE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment
Up to 136 weeks
Incidence of treatment-related TEAEs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Incidence of serious adverse events (SAEs)
Time Frame: Up to 136 weeks

Phase 2 and Phase 3

Any untoward medical occurrence that at any dose:

  • Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger)
  • Is life-threatening
  • Requires in-patient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability/incapacity
  • Is a congenital anomaly/birth defect
  • Is an important medical event
Up to 136 weeks
Incidence of adverse events of special interest (AESIs)
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 Serious or non-serious; is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it.
Up to 136 weeks
Incidence of immune-mediated adverse events (imAEs)
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 Immune-mediated AEs are thought to be caused by unrestrained cellular immune responses directed at normal host tissues. An imAE can occur shortly after the first dose or several months after the last dose of treatment. Early detection and management reduces the risk of severe drug induced toxicity
Up to 136 weeks
Occurrence of interruption of study drug(s) due to TEAEs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Occurrence of discontinuation of study drug(s) due to TEAEs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Occurrence of interruption of study drug(s) due to AESIs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Occurrence of discontinuation of study drug(s) due to AESIs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Occurrence of interruption of study drug(s) due to imAEs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Occurrence of discontinuation of study drug(s) due to imAEs
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 A unique set of toxicities thought to be caused by unrestrained cellular immune responses
Up to 136 weeks
Incidence of deaths due to TEAE
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Incidence of grade 3 to 4 laboratory abnormalities
Time Frame: Up to 136 weeks

Phase 2 and Phase 3

≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0]
Up to 136 weeks
ORR by investigator assessment, using RECIST 1.1
Time Frame: Up to 136 weeks
Phase 2
Up to 136 weeks
Disease control rate (DCR) by BICR
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 The proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD)
Up to 136 weeks
DCR by investigator assessment
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Time to tumor response (TTR) by BICR
Time Frame: Up to 136 weeks
Phase 2 and Phase 3 The time from randomization to the date of the first response of CR or PR (whichever is first recorded) for patients with confirmed CR or PR.
Up to 136 weeks
TTR by investigator assessment
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Duration of response (DOR) by BICR
Time Frame: Up to 5 years
Phase 2 and Phase 3 The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR.
Up to 5 years
DOR by investigator assessment
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Progression free survival (PFS) by BICR
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
PFS by investigator assessment
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Overall survival (OS)
Time Frame: Up to 5 years
Phase 2 The time from randomization to the date of death due to any cause
Up to 5 years
Change from baseline in patient-reported physical functioning per EORTC QLQ-C30
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer (EORTC QLQ-LC13)
Time Frame: Up to 5 years
Phase 2 and Phase 3 EORTC QLQ-LC 13 is a lung cancer specific module developed to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients
Up to 5 years
Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Change from baseline in patient-reported cough per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Change from baseline in patient-reported general health status per EuroQoL-5 Dimensions, 5-level Questionnaire-Visual Analogue Score (EQ-5D-5L VAS)
Time Frame: Up to 5 years
Phase 2 and Phase 3 The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine".
Up to 5 years
Change from baseline in patient-reported severity with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Time Frame: Up to 5 years
Phase 2 and Phase 3 PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.
Up to 5 years
Change from baseline in patient-reported interference with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Time Frame: Up to 5 years
Phase 2 and Phase 3
Up to 5 years
Concentrations of cemiplimab in serum
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Concentrations of fianlimab in serum
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Immunogenicity, as measured by ADA to cemiplimab
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Immunogenicity, as measured by NAb to cemiplimab
Time Frame: Up to 136 weeks
Phase 2 and Phase 3
Up to 136 weeks
Change from baseline in patient-reported global health status/quality of life (GHS/QoL) per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
Time Frame: Up to 5 years
Phase 2 and Phase 3 EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a GHS/QoL scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2023

Primary Completion (Estimated)

March 11, 2030

Study Completion (Estimated)

February 5, 2032

Study Registration Dates

First Submitted

March 14, 2023

First Submitted That Met QC Criteria

March 14, 2023

First Posted (Actual)

March 27, 2023

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R3767-ONC-2235
  • 2022-501483-18-00 (Registry Identifier: EUCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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