Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Non-Small Cell Lung Cancer, NSCLC, Anti-PD-1, Anti-CTLA-4, Immunotherapy
Brief summary
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.
Interventions
DRUGREGN4659
REGN4659 will be administered by intravenous (IV) infusion.
DRUGCemiplimab
Cemiplimab will be administered by intravenous (IV) infusion.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
KEY Inclusion Criteria: 1. Patients with histologically or cytologically documented squamous or non-squamous NSCLC with unresectable stage IIIB or stage IV disease 2. 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. 3. 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 4. 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
1. Expansion cohort(s) only: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime 2. 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 3. 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. 4. Radiation therapy within 2 weeks prior to enrollment and not recovered to baseline from any AE due to radiation 5. Patients who received prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody 6. Previous treatment with idelalisib (ZYDELIG®) at any time Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| REGN4659 and cemiplimab concentrations in serum over time | Up to week 126 |
| 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 |
Secondary
| Measure | 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 |
Countries
United States
Outcome results
None listed