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.

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Resectable Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Fianlimab
* Drug: Cemiplimab
* Drug: Pemetrexed
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Neoadjuvant therapy, Subsequent adjuvant therapy, Stage II to IIIB (N2), PeriOperative