Study of REGN4659 in Combination With Cemiplimab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The objective of this trial is to study REGN4659 and cemiplimab in treatment-experienced, non-small cell lung cancer (NSCLC) patients. There are 2 phases of this study: a dose escalation phase and a dose expansion phase.

Official Title
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A Phase 1 Study of REGN4659 (Anti-CTLA-4 mAb) in Combination With Cemiplimab (Anti-PD-1 mAb) in the Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: REGN4659
* Drug: Cemiplimab


Participation Criteria
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Eligibility Criteria
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KEY Inclusion Criteria: Patients with histologically or cytologically documented squamous or non-squamous NSCLC with unresectable stage IIIB or stage IV disease Combination dose escalation cohorts: Treatment-experienced patients who have received no more than 3 lines of systemic therapy including no more than 2 lines of cytotoxic chemotherapy, and for whom no available therapy has a high probability to convey clinical benefit. Dose escalation cohort C: Anti-PD-1/PD-L1 naïve patients who have received 1 to 2 prior lines of cytotoxic chemotherapy including a platinum doublet-containing regimen Expansion cohort(s): Anti-PD-1/PD-L1 experienced patients who have progressed while receiving therapy or within 6 months of stopping therapy for stage III or IV disease. Patients must not have permanently discontinued anti-PD-1/PD-L1 therapy due to treatment related AE. Patients must have received one line of anti-PD--1/PD-L1 immunotherapy. Patients may also have received one line of chemotherapy KEY Exclusion Criteria: Expansion cohort(s) only: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Patients must be off (immunosuppressive doses of) corticosteroid therapy Expansion cohort(s) only: Patients with tumors tested positive for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations or ROS1 fusions. Radiation therapy within 2 weeks prior to enrollment and not recovered to baseline from any AE due to radiation Patients who received prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody Previous treatment with idelalisib (ZYDELIG®) at any time 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cemiplimab Monotherapy<br>In a single dose escalation cohort, participants will receive cemiplimab alone. | Drug: Cemiplimab<br>* Cemiplimab will be administered by intravenous (IV) infusion.<br>* Other names: REGN2810;|
| Experimental: Combination Therapy<br>Dose Escalation cohorts: In 3 dose escalation cohorts, participants will receive a lead-in dose of REGN4659 followed by REGN4659 and cemiplimab in combination. In 4 dose escalation cohorts, participants will receive REGN4659 with cemiplimab in combination. Dose Expansion cohorts: In dose expansion cohorts, participants will receive combination regimens of REGN4659 and cemiplimab. | Drug: REGN4659<br>* REGN4659 will be administered by intravenous (IV) infusion.<br>Drug: Cemiplimab<br>* Cemiplimab will be administered by intravenous (IV) infusion.<br>* Other names: REGN2810;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of dose limiting toxicities (DLTs) during the dose escalation phase |  | Up to week 126 | 
| Rate of treatment emergent adverse events (TEAEs) |  | Up to week 126 | 
| Rate of immune-related adverse events (irAEs) |  | Up to week 126 | 
| Rate of serious adverse events (SAEs) |  | Up to week 126 | 
| Rate of deaths |  | Up to week 126 | 
| Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) |  | Up to week 126 | 
| Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during the dose expansion phase |  | Up to week 126 | 
| REGN4659 and cemiplimab concentrations in serum over time |  | Up to week 126 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR based on RECIST 1.1 during the dose escalation phase |  | Up to week 126 | 
| ORR based on immune-based therapy Response Evaluation Criteria (iRECIST) |  | Up to week 126 | 
| Best overall response (BOR) |  | Up to week 126 | 
| Duration of response (DOR) |  | Up to week 126 | 
| Disease control rate |  | Up to week 126 | 
| Progression-free-survival (PFS) based on RECIST 1.1 |  | Up to week 126 | 
| PFS based on iRECIST |  | Up to week 126 | 
| Overall survival (OS) |  | Up to week 126 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC, Anti-PD-1, Anti-CTLA-4, Immunotherapy