A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

Regeneron Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2

Conditions: Non Small Cell Lung Cancer; NSCLC

Treatments: Drug: REGN10597; Drug: Marlotamig; Drug: Cemiplimab; Drug: Platinum-based chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT06465329

2023-509806-31-00 (Registry Identifier)

R2810-ONC-2268

2023

Details and patient eligibility

About

This study will enroll adult participants with early-stage (stage II-IIIB) non-small cell lung cancer (NSCLC) for whom surgery is planned, in the resectable NSCLC portion.

The aim of the resectable NSCLC portion is to find out whether an investigational treatment (consisting of the immunotherapy drug cemiplimab plus chemotherapy plus a third drug) works better than cemiplimab plus chemotherapy without the additional drug.

For each investigational arm, the available data will be reviewed to decide whether safety testing with chemotherapy is needed before moving the treatment combination to the main resectable NSCLC portion of the study. If safety testing with chemotherapy is required, adult participants whose tumour has spread to other organs or cannot be removed by surgery, will be enrolled in the unresectable/metastatic NSCLC portion of the study called the "safety lead-in."

The aim of the unresectable/metastatic NSCLC safety lead-in portion is to evaluate the safety of the combination of Cemiplimab, chemotherapy, and an additional drug in participants with unresectable or metastatic NSCLC.

For the resectable NSCLC portion, the study is also looking at several other research questions, including:

• What are the side effects associated with the investigational treatments in comparison to the control treatment
• Do the investigational treatments or the control treatment have an effect on the type of surgery that is performed
• How much of the study drug(s) are in the blood at a given time
• Does the body make antibodies against the study drug(s) (which could make the drug(s) less effective or could lead to side effects)

For the unresectable/metastatic NSCLC portion, the study is also looking at several other research questions, including:

• What are the side effects associated with the additional drug in combination with cemiplimab and chemotherapy
• How does the additional drug work in combination with cemiplimab and chemotherapy

Enrollment: 184 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Neoadjuvant Resectable NSCLC General Key Inclusion Criteria:

1. Histologically confirmed stage II through IIIB (N2) NSCLC, that is considered resectable with curative intent, as described in the protocol
2. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1
3. Available formalin-fixed paraffin-embedded (FFPE) tumor sample blocks for submission, as described in the protocol
4. Eastern Cooperative Oncology Group Performance Status scale (ECOG PS) of 0 to 1
5. Adequate organ and bone marrow function, as described in the protocol

Arm Specific Inclusion Criteria:

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic disease), who received no prior systemic treatment for recurrent or metastatic NSCLC
2. Availability of an archival or on-trial FFPE tumor tissue sample
3. ECOG performance status of 0 or 1
4. Per investigator judgment, life expectancy of at least 3 months

Neoadjuvant Resectable NSCLC General Key Exclusion Criteria:

1. Any systemic anti-cancer therapy or radiotherapy for the current tumor, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which an approved targeted therapy is available or for which perioperative chemoimmunotherapy is not considered an appropriate standard of care treatment, as described in the protocol
3. Presence of grade≥ 2 peripheral neuropathy
4. Another malignancy that is progressing or requires active treatment, as described in the protocol

Arm Specific Exclusion Criteria:

Neoadjuvant Resectable NSCLC - Arm 1:

1. Grade ≥3 hypercalcemia, as defined in the protocol
2. Any central nervous system (CNS) pathology that could increase the risk of immune effector cell-associated neurotoxicity syndrome (ICANS), as described in the protocol
3. Has marked baseline prolongation of the time from the start of the Q wave to the end of the T wave in electrocardiogram (QT)/corrected QT interval (QTc) interval or risk factors for prolonged QTc, as described in the protocol

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which a chemotherapy plus programmed cell death protein 1 (PD1) inhibitor backbone is not the appropriate initial therapy as standard of care
3. Known allergy or hypersensitivity to any components of trial interventions
4. Any condition requiring ongoing/continuous corticosteroid therapy, as described in the protocol

Neoadjuvant Resectable NSCLC - Arm 2:

1. History of encephalitis, meningitis, organic brain disease, or uncontrolled seizures within 1 year prior to the first dose of trial interventions.

Note: Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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184 participants in 4 patient groups

Neoadjuvant Resectable NSCLC - Control Arm

Active Comparator group

Treatment:

Drug: Cemiplimab

Drug: Platinum-based chemotherapy

Neoadjuvant Resectable NSCLC - Arm 1

Experimental group

Treatment:

Drug: Cemiplimab

Drug: Platinum-based chemotherapy

Drug: Marlotamig

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2

Experimental group

Treatment:

Drug: Cemiplimab

Drug: Platinum-based chemotherapy

Drug: REGN10597

Neoadjuvant Resectable NSCLC - Arm 2

Experimental group

Treatment:

Drug: Cemiplimab

Drug: Platinum-based chemotherapy

Drug: REGN10597