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

Resectable Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06161441
• Other study ID #: R3767-ONC-2266
• Secondary ID: 2023-505172-29-0
• Status: Recruiting
• Phase: Phase 2
• Start date: June 7, 2024
• Est. completion date: April 19, 2029

Study information

• Verified date: June 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 stage 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: April 19, 2029
• Est. primary completion date: September 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Resectable Non-small Cell Lung Cancer

Intervention

Drug:
• Fianlimab
Administered intravenously (IV) every 3 weeks (Q3W)
• Cemiplimab
Administered IV Q3W
• Pemetrexed
Administered IV Q3W
• Paclitaxel
Administered IV Q3W
• Carboplatin
Administered IV Q3W
• Cisplatin
Administered IV Q3W
• Placebo
Administered IV Q3W

Locations

Country	Name	City	State
United States	Clermont Oncology Center	Clermont	Florida
United States	Mid-Florida Hematology & Oncology Centers, PA	Orange City	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples		Up to 24 months
Secondary	Event-Free Survival (EFS)		Up to 3 years
Secondary	Major pathological response (MPR) by BIPR in post-treatment resected tumor samples		Up to 24 months
Secondary	MPR by local pathology review in post-treatment resected tumor samples		Up to 24 months
Secondary	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
Secondary	Occurrence of Adverse events (AEs)		Up to 5 years
Secondary	Occurrence of Treatment-emergent adverse event (TEAEs)		Up to 5 years
Secondary	Occurrence of Serious adverse events (SAEs)		Up to 5 years
Secondary	Occurrence of Adverse events of special interest (AESIs)		Up to 5 years
Secondary	Occurrence of immune-mediated adverse events (imAEs)		Up to 5 years
Secondary	Occurrence of interruption and discontinuation of study drug(s) due to TEAE		Up to 5 years
Secondary	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
Secondary	Occurrence of death due to TEAE		Up to 5 years
Secondary	Concentrations of cemiplimab in serum		Up to 30 months
Secondary	Concentrations of fianlimab in serum		Up to 30 months
Secondary	Anti-drug antibodies (ADA) to fianlimab in serum over time		Up to 30 months
Secondary	ADA to cemiplimab in serum over time		Up to 30 months
Secondary	Percentage of patients with definitive surgery		Up to 24 months
Secondary	Percentage of patients with cancelled surgery		Up to 24 months
Secondary	Percentage of patients with delayed surgery		Up to 24 months
Secondary	Completeness of resection (R0, R1, R2, Rx)		Up to 24 months
Secondary	Length in delay of surgery		Up to 24 months
Secondary	Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other)		Up to 24 months
Secondary	Median length of hospital stay		Up to 24 months
Secondary	Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy)		Up to 24 months
Secondary	Incidence of peri operative AE associated with surgery		Up to 90 days post-surgery
Secondary	Incidence of peri operative SAE associated with surgery		Up to 90 days post-surgery
Secondary	Incidence of post operative AE associated with surgery		Up to 90 days post-surgery
Secondary	Incidence of post operative SAE associated with surgery		Up to 90 days post-surgery
Secondary	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
Secondary	Overall change in patient-reported physical functioning per EORTC QLQ-C30		Up to 5 years
Secondary	Overall change in patient-reported role functioning per EORTC QLQ-C30		Up to 5 years
Secondary	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
Secondary	Overall change in patient-reported dyspnea per EORTC QLQ-LC13		Up to 5 years
Secondary	Overall change in patient-reported cough per EORTC QLQ-LC13		Up to 5 years
Secondary	Overall change in patient-reported composite of chest pain, dyspnea, and cough per EORTC QLQ-LC13		Up to 5 years
Secondary	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
Secondary	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".	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported role functioning per EORTC QLQ-C30		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13		Up to 5 years
Secondary	Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13		Up to 5 years