A Trial to Learn if the Combination of Fianlimab, Cemiplimab, and Chemotherapy is Safe and Works Better Than the Combination of Cemiplimab and Chemotherapy in Adult Patients With Non-small Cell Lung Cancer That Can be Treated With Surgery.

A Phase 2 Peri-Operative Trial of Fianlimab and Cemiplimab in Combination With Chemotherapy Versus Cemiplimab in Combination With Chemotherapy in Patients With Resectable Early Stage (Stage II to IIIB [N2]) NSCLC

This study is researching an experimental drug called fianlimab (also called REGN3767) with two other medications called cemiplimab (also called LIBTAYO) and platinum-doublet chemotherapy, individually called a "study drug" or collectively called "study drugs", when combined in this study. The study is being conducted in patients who have stage II to IIIB (N2) non-small cell lung cancer (NSCLC) that can be treated with surgery.

The aim of the study is to see how effective the combination of fianlimab, cemiplimab, and chemotherapy is in comparison with cemiplimab and chemotherapy as peri-operative therapy in participants with NSCLC.

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 affect your quality of life

Study Overview

• Status: Not yet recruiting
• Conditions: Resectable Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Cemiplimab; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Placebo; Drug: Fianlimab

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Patients with newly diagnosed, histologically confirmed, fully resectable stage II to IIIB (N2) NSCLC as per American Joint Committee on Cancer (AJCC) version 8
2. For patients with evidence of mediastinal adenopathy on imaging, mediastinal lymph node sampling is required as defined in the protocol
3. All patients must have disease status showing no evidence of distant metastases documented by a complete physical examination and imaging studies performed within 4 weeks prior to randomization as defined in the protocol
4. A patient must have an evaluable Programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) result as defined in the protocol
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate bone marrow, hepatic and kidney function as defined in the protocol

Key Exclusion Criteria:

1. Any evidence of locally advanced unresectable or metastatic disease as defined in the protocol
2. Patients with tumors with known Epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations as defined in the protocol
3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection as defined in the protocol
4. Treatment with anti-cancer therapy including immunotherapy, chemotherapy, radiotherapy, or biological therapy in the 3 years prior to randomization. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
5. Patients with a history of myocarditis

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab	Drug: Cemiplimab; Administered IV Q3W; Other Names: REGN2810; Libtayo; Drug: Pemetrexed; Administered IV Q3W; Other Names: Alimta; Drug: Paclitaxel; Administered IV Q3W; Other Names: Taxol; Drug: Carboplatin; Administered IV Q3W; Other Names: Paraplatin; Drug: Cisplatin; Administered IV Q3W; Other Names: Platinol; Drug: Placebo; Administered IV Q3W
Experimental: Arm B; Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab	Drug: Cemiplimab; Administered IV Q3W; Other Names: REGN2810; Libtayo; Drug: Pemetrexed; Administered IV Q3W; Other Names: Alimta; Drug: Paclitaxel; Administered IV Q3W; Other Names: Taxol; Drug: Carboplatin; Administered IV Q3W; Other Names: Paraplatin; Drug: Cisplatin; Administered IV Q3W; Other Names: Platinol; Drug: Fianlimab; Administered intravenously (IV) every 3 weeks (Q3W); Other Names: REGN3767
Experimental: Arm C; Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab	Drug: Cemiplimab; Administered IV Q3W; Other Names: REGN2810; Libtayo; Drug: Pemetrexed; Administered IV Q3W; Other Names: Alimta; Drug: Paclitaxel; Administered IV Q3W; Other Names: Taxol; Drug: Carboplatin; Administered IV Q3W; Other Names: Paraplatin; Drug: Cisplatin; Administered IV Q3W; Other Names: Platinol; Drug: Fianlimab; Administered intravenously (IV) every 3 weeks (Q3W); Other Names: REGN3767

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)		Up to 3 years
Major pathological response (MPR) by BIPR in post-treatment resected tumor samples		Up to 24 months
MPR by local pathology review in post-treatment resected tumor samples		Up to 24 months
Tumor response to neoadjuvant therapy per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria by investigator assessment		Up to 24 months
Occurrence of Adverse events (AEs)		Up to 5 years
Occurrence of Treatment-emergent adverse event (TEAEs)		Up to 5 years
Occurrence of Serious adverse events (SAEs)		Up to 5 years
Occurrence of Adverse events of special interest (AESIs)		Up to 5 years
Occurrence of immune-mediated adverse events (imAEs)		Up to 5 years
Occurrence of interruption and discontinuation of study drug(s) due to TEAE		Up to 5 years
Occurrence of laboratory abnormalities	Grade ≥3 per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) including standard hematology, chemistry, urinalysis, and other lab tests	Up to 5 years
Occurrence of death due to TEAE		Up to 5 years
Concentrations of cemiplimab in serum		Up to 30 months
Concentrations of fianlimab in serum		Up to 30 months
Anti-drug antibodies (ADA) to fianlimab in serum over time		Up to 30 months
ADA to cemiplimab in serum over time		Up to 30 months
Percentage of patients with definitive surgery		Up to 24 months
Percentage of patients with cancelled surgery		Up to 24 months
Percentage of patients with delayed surgery		Up to 24 months
Completeness of resection (R0, R1, R2, Rx)		Up to 24 months
Length in delay of surgery		Up to 24 months
Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other)		Up to 24 months
Median length of hospital stay		Up to 24 months
Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy)		Up to 24 months
Incidence of peri operative AE associated with surgery		Up to 90 days post-surgery
Incidence of peri operative SAE associated with surgery		Up to 90 days post-surgery
Incidence of post operative AE associated with surgery		Up to 90 days post-surgery
Incidence of post operative SAE associated with surgery		Up to 90 days post-surgery
Overall change in patient-reported global health status/QoL per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	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.	Up to 5 years
Overall change in patient-reported physical functioning per EORTC QLQ-C30		Up to 5 years
Overall change in patient-reported role functioning per EORTC QLQ-C30		Up to 5 years
Overall change in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.	Up to 5 years
Overall change in patient-reported dyspnea per EORTC QLQ-LC13		Up to 5 years
Overall change in patient-reported cough per EORTC QLQ-LC13		Up to 5 years
Overall change in patient-reported composite of chest pain, dyspnea, and cough per EORTC QLQ-LC13		Up to 5 years
Change in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) index	The EQ-5D-5L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-level scale: no problems, slight problems, moderate problems, severe problems and extreme problems	Up to 5 years
Changein patient-reported general health status per Visual analogue scale (VAS) scores	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
Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30		Up to 5 years
Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30		Up to 5 years
Time until definitive deterioration in patient-reported role functioning per EORTC QLQ-C30		Up to 5 years
Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13		Up to 5 years
Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13		Up to 5 years
Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13		Up to 5 years
Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13		Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): March 5, 2024
• Primary Completion (Estimated): September 28, 2025
• Study Completion (Estimated): April 19, 2029

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Actual): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Neoadjuvant therapy; Stage II to IIIB (N2); Subsequent adjuvant therapy; PeriOperative
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed; Cemiplimab
• Other Study ID Numbers: R3767-ONC-2266; 2023-505172-29-00 (Other Identifier: EU CTR 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 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