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

Phase 2Active Not RecruitingNCT06161441

Regeneron Pharmaceuticals195 enrolled

Overview

This study is researching an experimental drug called fianlimab (also called REGN3767) with two other medications called cemiplimab 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 resectable 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 the blood at different times * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects) * How administering the study drugs might affect quality of life

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

195

Conditions

Resectable Non-small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (123)

Clermont Oncology Center

Clermont, Florida, United States

University of Illinois

Chicago, Illinois, United States

University of Kansas Cancer Center-Westwood

Westwood, Kansas, United States

Henry Ford Health System

Detroit, Michigan, United States

Mercy South

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples

Time frame: Up to 24 months

Secondary Outcomes

Event-Free Survival (EFS)

Time frame: Up to 3 years

Major pathological response (MPR) by BIPR in post-treatment resected tumor samples

Time frame: Up to 24 months

MPR by local pathology review in post-treatment resected tumor samples

Time frame: 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

Time frame: Up to 24 months

Occurrence of Adverse events (AEs)

Time frame: Up to 5 years

Occurrence of Treatment-emergent adverse event (TEAEs)

Time frame: Up to 5 years

Occurrence of Serious adverse events (SAEs)

Time frame: Up to 5 years

Occurrence of Adverse events of special interest (AESIs)

Time frame: Up to 5 years

Occurrence of immune-mediated adverse events (imAEs)

Time frame: Up to 5 years

Occurrence of interruption and discontinuation of study drug(s) due to TEAE

Time frame: 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

Time frame: Up to 5 years

Occurrence of death due to TEAE

Time frame: Up to 5 years

Concentrations of cemiplimab in serum

Time frame: Up to 30 months

Concentrations of fianlimab in serum

Time frame: Up to 30 months

Anti-drug antibodies (ADA) to fianlimab in serum over time

Time frame: Up to 30 months

ADA to cemiplimab in serum over time

Time frame: Up to 30 months

Percentage of patients with definitive surgery

Time frame: Up to 24 months

Percentage of patients with cancelled surgery

Time frame: Up to 24 months

Percentage of patients with delayed surgery

Time frame: Up to 24 months

Completeness of resection (R0, R1, R2, Rx)

Time frame: Up to 24 months

Length in delay of surgery

Time frame: Up to 24 months

Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other)

Time frame: Up to 24 months

Median length of hospital stay

Time frame: Up to 24 months

Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy)

Time frame: Up to 24 months

Incidence of peri operative AE associated with surgery

Time frame: Up to 90 days post-surgery

Incidence of peri operative SAE associated with surgery

Time frame: Up to 90 days post-surgery

Incidence of post operative AE associated with surgery

Time frame: Up to 90 days post-surgery

Incidence of post operative SAE associated with surgery

Time frame: 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.

Time frame: Up to 5 years

Overall change in patient-reported physical functioning per EORTC QLQ-C30

Time frame: Up to 5 years

Overall change in patient-reported role functioning per EORTC QLQ-C30

Time frame: 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.

Time frame: Up to 5 years

Overall change in patient-reported dyspnea per EORTC QLQ-LC13

Time frame: Up to 5 years

Overall change in patient-reported cough per EORTC QLQ-LC13

Time frame: Up to 5 years

Overall change in patient-reported composite of chest pain, dyspnea, and cough per EORTC QLQ-LC13

Time frame: 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

Time frame: Up to 5 years

Change in 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".

Time frame: 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

Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30

Time frame: Up to 5 years

Time until definitive deterioration in patient-reported role functioning per EORTC QLQ-C30

Time frame: Up to 5 years

Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13

Time frame: Up to 5 years

Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13

Time frame: Up to 5 years

Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13

Time frame: 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