Clinical trial NCT03580694: Study of REGN4659 in Combination With Cemiplimab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Non-Small Cell Lung Cancer
NSCLC
Anti-PD-1
Anti-CTLA-4
Immunotherapy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-07-09
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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/ exclusion criteria apply

Primary outcomes:
measure: Rate of dose limiting toxicities (DLTs) during the dose escalation phase
timeFrame: Up to week 126
measure: Rate of treatment emergent adverse events (TEAEs)
timeFrame: Up to week 126
measure: Rate of immune-related adverse events (irAEs)
timeFrame: Up to week 126
measure: Rate of serious adverse events (SAEs)
timeFrame: Up to week 126
measure: Rate of deaths
timeFrame: Up to week 126
measure: Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE])
timeFrame: Up to week 126
measure: Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during the dose expansion phase
timeFrame: Up to week 126
measure: REGN4659 and cemiplimab concentrations in serum over time
timeFrame: Up to week 126
Secondary outcomes:
measure: ORR based on RECIST 1.1 during the dose escalation phase
timeFrame: Up to week 126
measure: ORR based on immune-based therapy Response Evaluation Criteria (iRECIST)
timeFrame: Up to week 126
measure: Best overall response (BOR)
timeFrame: Up to week 126
measure: Duration of response (DOR)
timeFrame: Up to week 126
measure: Disease control rate
timeFrame: Up to week 126
measure: Progression-free-survival (PFS) based on RECIST 1.1
timeFrame: Up to week 126
measure: PFS based on iRECIST
timeFrame: Up to week 126
measure: Overall survival (OS)
timeFrame: Up to week 126
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Regeneron Investigational Site
state: Illinois
city: Grand Rapids
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Charlotte
country: United States
facility: Regeneron Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Regeneron Investigational Site
state: Oklahoma
city: Nashville
country: United States
facility: Regeneron Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: Regeneron Investigational Site
state: Texas
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: