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
- Conditions
- Resectable Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06161441
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- Patients with newly diagnosed, histologically confirmed, fully resectable stage II to IIIB (N2) NSCLC as per American Joint Committee on Cancer (AJCC) version 8
- For patients with evidence of mediastinal adenopathy on imaging, mediastinal lymph node sampling is required as defined in the protocol
- 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
- A patient must have an evaluable Programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) result as defined in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate bone marrow, hepatic and kidney function as defined in the protocol
Key
- Any evidence of locally advanced unresectable or metastatic disease as defined in the protocol
- Patients with tumors with known Epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations as defined in the protocol
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection as defined in the protocol
- 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.
- Patients with a history of myocarditis
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B Fianlimab Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm B Carboplatin Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm B Cemiplimab Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm A Cemiplimab Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm A Paclitaxel Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm B Paclitaxel Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm C Paclitaxel Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab Arm A Placebo Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm A Carboplatin Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm C Fianlimab Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab Arm C Carboplatin Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab Arm B Pemetrexed Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm A Pemetrexed Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm A Cisplatin Randomized 1:1:1 Neoadjuvant period: placebo + cemiplimab + platinum doublet chemotherapy Adjuvant period: placebo + cemiplimab Arm C Cemiplimab Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab Arm B Cisplatin Randomized 1:1:1 Neoadjuvant period: fianlimab high dose + cemiplimab + platinum doublet chemotherapy Adjuvant period: fianlimab high dose + cemiplimab Arm C Pemetrexed Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab Arm C Cisplatin Randomized 1:1:1 Neoadjuvant period: fianlimab low dose + cemiplimab + platinum doublet chemotherapy Adjuvant Period: fianlimab low dose + cemiplimab
- Primary Outcome Measures
Name Time Method 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
Name Time Method Percentage of patients with definitive surgery Up to 24 months Percentage of patients with cancelled surgery Up to 24 months Median length of hospital stay Up to 24 months Anti-drug antibodies (ADA) to fianlimab in serum over time Up to 30 months Major pathological response (MPR) by BIPR in post-treatment resected tumor samples Up to 24 months Occurrence of interruption and discontinuation of study drug(s) due to TEAE Up to 5 years Concentrations of fianlimab in serum Up to 30 months Event-Free Survival (EFS) Up to 3 years 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 Treatment-emergent adverse event (TEAEs) 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 Concentrations of cemiplimab in serum Up to 30 months MPR by local pathology review in post-treatment resected tumor samples Up to 24 months Occurrence of Adverse events (AEs) Up to 5 years Occurrence of Serious adverse events (SAEs) Up to 5 years Occurrence of laboratory abnormalities Up to 5 years 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
Occurrence of death due to TEAE Up to 5 years ADA to cemiplimab in serum over time Up to 30 months Overall change in patient-reported role functioning per EORTC QLQ-C30 Up to 5 years Percentage of patients with delayed surgery Up to 24 months Completeness of resection (R0, R1, R2, Rx) Up to 24 months Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy) Up to 24 months Overall change in patient-reported physical 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) Up to 5 years 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.
Change in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) index Up to 5 years 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
Length in delay of surgery Up to 24 months Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other) Up to 24 months Incidence of post operative AE associated with surgery Up to 90 days post-surgery 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 Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 Up to 5 years 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 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) Up to 5 years 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.
Overall change in patient-reported dyspnea per EORTC QLQ-LC13 Up to 5 years Change in patient-reported general health status per Visual analogue scale (VAS) scores Up to 5 years 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 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 cough 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 composite of chest pain, dyspnea and cough per EORTC QLQ-LC13 Up to 5 years
Trial Locations
- Locations (122)
Cluj County Clinical Emergency Hospital
🇷🇴Cluj-Napoca, Cluj, Romania
Hospital General Universitario Elche
🇪🇸Elche, Alicante, Spain
Ankara University Faculty of Medicine
Ankara, Turkey (Türkiye)
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
Istanbul, Turkey (Türkiye)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Clermont Oncology Center
🇺🇸Clermont, Florida, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, 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
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