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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Pemetrexed; Drug: fianlimab; Drug: Cisplatin; Drug: Paclitaxel; Drug: cemiplimab; Drug: Placebo; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05800015

2022-501577-40-00 (Registry Identifier)

R3767-ONC-2236

Details and patient eligibility

About

This 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". '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

Enrollment: 950 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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, expression results (regardless of expression level) 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 a valid PD-L1 result, regardless of expression level, using an assay as 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 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 defined in the protocol.

Key Exclusion Criteria:

1. 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.

2. Patients with tumors tested positive for actionable epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS oncogene 1 (ROS1) fusions, as described in the protocol.

3. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.

4. 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.

5. 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).

6. 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.

7. 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.

8. 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 as an adjuvant or neoadjuvant therapy such as 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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950 participants in 5 patient groups

Phase 2 - Arm A

Experimental group

Description:

Randomized 1:1:1 fianlimab (higher dose) + cemiplimab + platinum-doublet chemotherapy

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: cemiplimab

Drug: Cisplatin

Drug: Pemetrexed

Drug: fianlimab

Phase 2 - Arm B

Experimental group

Description:

Randomized 1:1:1 fianlimab (lower dose) + cemiplimab + platinum-doublet chemotherapy

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: cemiplimab

Drug: Cisplatin

Drug: Pemetrexed

Drug: fianlimab

Phase 2 - Arm C

Experimental group

Description:

Randomized 1:1:1 cemiplimab + platinum-doublet chemotherapy + placebo

Treatment:

Drug: Carboplatin

Drug: Placebo

Drug: Paclitaxel

Drug: cemiplimab

Drug: Cisplatin

Drug: Pemetrexed

Phase 3 - Arm A or B

Experimental group

Description:

Randomized 1:1 fianlimab (chosen dose) + cemiplimab + platinum-doublet chemotherapy

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: cemiplimab

Drug: Cisplatin

Drug: Pemetrexed

Drug: fianlimab

Phase 3 - Arm C

Experimental group

Description:

Randomized 1:1 cemiplimab + platinum-doublet chemotherapy + placebo

Treatment:

Drug: Carboplatin

Drug: Placebo

Drug: Paclitaxel

Drug: cemiplimab

Drug: Cisplatin

Drug: Pemetrexed