A Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05800015

Collaborator

(none)

950

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The study is researching an investigational drug called fianlimab (also called REGN3767) with two other medications called cemiplimab and chemotherapy, individually called a "study drug" or collectively called "study drugs" in this form. 'Investigational' means that the study drug is not approved for use outside of this study by any Health Authority. Examples of chemotherapy drugs include the following: Paclitaxel plus carboplatin, and Pemetrexed plus cisplatin. The study is being conducted in patients who have advanced non-small cell lung cancer (NSCLC).

The aim of the study is to see how effective the combination of fianlimab, cemiplimab, and chemotherapy is for treating advanced NSCLC, in comparison with cemiplimab and chemotherapy.

The study is looking at several other research questions, including:

What side effects may happen from taking the study drugs
How much of each 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

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: fianlimab Drug: cemiplimab Drug: Pemetrexed Drug: Paclitaxel Drug: Carboplatin Drug: Cisplatin Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

950 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind Phase 2/3 Study of Fianlimab (Anti-LAG-3 Antibody), Cemiplimab (Anti-PD-1 Antibody), and Chemotherapy Versus Cemiplimab and Chemotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Irrespective of PD-L1 Expression Levels

Anticipated Study Start Date :

Apr 28, 2023

Anticipated Primary Completion Date :

May 27, 2031

Anticipated Study Completion Date :

May 27, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2 - Arm A Randomized 1:1:1 fianlimab (higher dose) + cemiplimab + platinum-doublet chemotherapy	Drug: fianlimab Administered intravenously (IV) every 3 weeks (Q3W) Other Names: REGN3767 Drug: cemiplimab Administered IV Q3W Other Names: REGN2810 Libtayo Drug: Pemetrexed IV Infusion, Q3W Other Names: Alimta Drug: Paclitaxel IV Infusion, Q3W Drug: Carboplatin IV Infusion, Q3W Other Names: Paraplatin Drug: Cisplatin IV infusion, Q3W Other Names: Platinol
Experimental: Phase 2 - Arm B Randomized 1:1:1 fianlimab (lower dose) + cemiplimab + platinum-doublet chemotherapy	Drug: fianlimab Administered intravenously (IV) every 3 weeks (Q3W) Other Names: REGN3767 Drug: cemiplimab Administered IV Q3W Other Names: REGN2810 Libtayo Drug: Pemetrexed IV Infusion, Q3W Other Names: Alimta Drug: Paclitaxel IV Infusion, Q3W Drug: Carboplatin IV Infusion, Q3W Other Names: Paraplatin Drug: Cisplatin IV infusion, Q3W Other Names: Platinol
Experimental: Phase 2 - Arm C Randomized 1:1:1 cemiplimab + platinum-doublet chemotherapy + placebo	Drug: cemiplimab Administered IV Q3W Other Names: REGN2810 Libtayo Drug: Pemetrexed IV Infusion, Q3W Other Names: Alimta Drug: Paclitaxel IV Infusion, Q3W Drug: Carboplatin IV Infusion, Q3W Other Names: Paraplatin Drug: Cisplatin IV infusion, Q3W Other Names: Platinol Drug: Placebo IV infusion, Q3W
Experimental: Phase 3 - Arm A or B Randomized 1:1 fianlimab (chosen dose) + cemiplimab + platinum-doublet chemotherapy	Drug: fianlimab Administered intravenously (IV) every 3 weeks (Q3W) Other Names: REGN3767 Drug: cemiplimab Administered IV Q3W Other Names: REGN2810 Libtayo Drug: Pemetrexed IV Infusion, Q3W Other Names: Alimta Drug: Paclitaxel IV Infusion, Q3W Drug: Carboplatin IV Infusion, Q3W Other Names: Paraplatin Drug: Cisplatin IV infusion, Q3W Other Names: Platinol
Experimental: Phase 3 - Arm C Randomized 1:1 cemiplimab + platinum-doublet chemotherapy + placebo	Drug: cemiplimab Administered IV Q3W Other Names: REGN2810 Libtayo Drug: Pemetrexed IV Infusion, Q3W Other Names: Alimta Drug: Paclitaxel IV Infusion, Q3W Drug: Carboplatin IV Infusion, Q3W Other Names: Paraplatin Drug: Cisplatin IV infusion, Q3W Other Names: Platinol Drug: Placebo IV infusion, Q3W

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) as assessed by blinded independent review committee (BICR) using RECIST 1.1 [Up to 136 Weeks]
Phase 2 ORR is defined as proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR).
Overall Survival (OS) [Up to 5 years]
Phase 3 Defined as the time from randomization to the date of death due to any cause

Secondary Outcome Measures

Incidence of treatment-emergent adverse event (TEAEs) [Up to 108 weeks]
Phase 2 & 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
Incidence of treatment-related TEAEs [Up to 108 weeks]
Phase 2 & Phase 3
Incidence of serious adverse events (SAEs) [Up to 108 weeks]
Phase 2 & 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
Incidence of adverse events of special interest (AESIs) [Up to 108 weeks]
Phase 2 & 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.
Incidence of immune-mediated adverse events (imAEs) [Up to 108 weeks]
Phase 2 & 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
Occurrence of interruption of study drug(s) due to AEs [Up to 108 weeks]
Phase 2 & Phase 3
Occurrence of discontinuation of study drug(s) due to AEs [Up to 108 weeks]
Phase 2 & Phase 3
Incidence of deaths due to TEAE [Up to 108 weeks]
Phase 2 & Phase 3
Incidence of grade 3-4 laboratory abnormalities [Up to 108 weeks]
Phase 2 & Phase 3 ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0]
ORR by investigator assessment using RECIST 1.1 [Up to 136 Weeks]
Phase 2 & Phase 3
Disease control rate (DCR) by BICR [Up to 136 Weeks]
Phase 2 and Phase 3 DCR is defined as CR + PR + stable disease (SD)
DCR by investigator assessment [Up to 136 Weeks]
Phase 2 and Phase 3 DCR is defined as CR + PR + stable disease (SD)
Time to tumor response (TTR) by BICR [Up to 136 Weeks]
Phase 2 and Phase 3 TTR is defined as 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.
TTR by investigator assessment [Up to 136 Weeks]
Phase 2 and Phase 3 TTR is defined as 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
Duration of response (DOR) by BICR [Up to 5 Years]
Phase 2 and Phase 3 DOR is defined as 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
DOR by investigator assessment [Up to 5 Years]
Phase 2 and Phase 3 DOR is defined as 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
Progression free survival (PFS) by BICR [Up to 5 Years]
Phase 2 and Phase 3 PFS is defined as the time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier
PFS by investigator assessment [Up to 5 Years]
Phase 2 and Phase 3 PFS is defined as the time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier
OS [Up to 5 Years]
Phase 2 Defined as the time from randomization to the date of death due to any cause
Change from baseline in patient-reported Global health status/QoLper European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Up to 108 weeks]
Phase 2 & Phase 3 EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (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.
Change from baseline in physical functioning per EORTC QLQ-C30 [Up to 108 weeks]
Phase 2 & Phase 3
Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [Up to 108 weeks]
Phase 2 & 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
Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Change from baseline in patient-reported cough per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Time until definitive deterioration in a composite of these three symptoms: patient-reported chest pain, dyspnea and cough per EORTC QLQ-LC13 [Up to 108 weeks]
Phase 2 & Phase 3
Change from baseline in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) VAS [Up to 108 weeks]
Phase 2 & 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".
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) [Up to 108 weeks]
Phase 2 & 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.
Change from baseline in patient-reported interference with usual or daily activities due to fatigue per the PRO-CTCAE [Up to 108 weeks]
Phase 2 & Phase 3
Concentrations of cemiplimab in serum [Up to 136 weeks]
Phase 2 & Phase 3
Concentrations of fianlimab in serum [Up to 136 weeks]
Phase 2 & Phase 3
Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab [Up to 136 weeks]
Phase 2 & Phase 3
Immunogenicity, as measured by ADA to cemiplimab [Up to 136 weeks]
Phase 2 & Phase 3
Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab [Up to 136 weeks]
Phase 2 & Phase 3
Immunogenicity, as measured by NAb to cemiplimab [Up to 136 weeks]
Phase 2 & Phase 3

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key 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 tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol
A valid result of PD-L1, regardless of expression level using an assay as performed by a central laboratory.
Available tissue for retrospective testing using an assay as performed by a central laboratory.
At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per 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 ≤1.
Adequate organ and bone marrow function as defined in the protocol.

Key Exclusion Criteria:

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 estimated glomerular filtration rate (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS oncogene 1 (ROS1) fusions. All patients will have tumor evaluated for EGFR mutations, ALK rearrangement, and ROS1 fusions confirmed by a central laboratory when local laboratory results are not available.
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:
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.
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.
Prior exposure to other immunomodulatory or vaccine therapies such as anti-CTLA-4 antibodies as long as the last dose is >3 months prior to enrollment. Immune-mediated AEs must be resolved to CTCAE grade ≤1 or baseline by the time of enrollment. Endocrine immunemediated AEs controlled with hormonal or other nonimmunosuppressive therapies without resolution prior to enrollment are allowed.