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

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

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.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Cemiplimab; Drug: REGN4659

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Regeneron Investigational Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Regeneron Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Regeneron Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Regeneron Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Regeneron Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Regeneron Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cemiplimab Monotherapy; In a single dose escalation cohort, participants will receive cemiplimab alone.	Drug: Cemiplimab; Cemiplimab will be administered by intravenous (IV) infusion.; Other Names: REGN2810
EXPERIMENTAL: Combination Therapy; 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: Cemiplimab; Cemiplimab will be administered by intravenous (IV) infusion.; Other Names: REGN2810; Drug: REGN4659; REGN4659 will be administered by intravenous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2018
• Primary Completion (ACTUAL): December 4, 2019
• Study Completion (ACTUAL): December 4, 2019

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (ACTUAL): July 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Immunotherapy; Anti-PD-1; Anti-CTLA-4
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R4659-ONC-1795

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No