Clinical Trials /

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

NCT03580694

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: R4659-ONC-1795
  • NCT ID: NCT03580694

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
REGN4659Combination Therapy
CemiplimabREGN2810Cemiplimab Monotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cemiplimab MonotherapyExperimentalIn a single dose escalation cohort, participants will receive cemiplimab alone.
  • Cemiplimab
Combination TherapyExperimentalDose 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.
  • REGN4659
  • Cemiplimab

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 is expected to convey clinical
             benefit.

          3. Cemiplimab monotherapy cohort: 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of dose limiting toxicities (DLTs) during the dose escalation phase
Time Frame:Up to day 42
Safety Issue:
Description:PK variables may include, but are not limited to, the following: Area under the concentration-time curve (AUC) over a dosing interval, the peak concentration and last positive (quantifiable) concentration

Secondary Outcome Measures

Measure:ORR based on RECIST 1.1 during the dose escalation phase
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:ORR based on immune-based therapy Response Evaluation Criteria (iRECIST)
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Best overall response (BOR)
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Progression-free-survival (PFS) based on RECIST 1.1
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:PFS based on iRECIST
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Up to week 126
Safety Issue:
Description:
Measure:Quantitation of percent change in absolute inducible co-stimulator (ICOS)+ cluster of differentiation 4 (CD4) T-cells within each dose cohort
Time Frame:Up to week 102
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • Non-Small Cell Lung Cancer
  • NSCLC
  • Anti-PD-1
  • Anti-CTLA-4
  • Immunotherapy

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