Clinical Trials /

Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Platinum-Resistant Ovarian Cancer

NCT03564340

Description:

The primary objectives of the Dose Escalation Phase are to assess the safety and pharmacokinetics (PK) in order to determine a maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of REGN4018 as monotherapy and in combination with cemiplimab. In the Dose Expansion Phase, the primary objectives are to assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as determined by the objective response rate (ORR). The secondary objectives of the Dose Escalation Phase are to assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as determined by ORR. In the Dose Expansion Phase, the secondary objectives are to characterize the safety profile in each expansion cohort and characterize the PK of REGN4018 as monotherapy and in combination with cemiplimab. In both the Dose Escalation and Dose Expansion Phases, secondary objectives are to assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR based on iRECIST, best overall response (BOR), duration of response (DOR), disease control rate, and progression-free survival (PFS) and to assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Platinum-Resistant Ovarian Cancer
  • Official Title: A Phase 1/2 Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Platinum-Resistant Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: R4018-ONC-1721
  • NCT ID: NCT03564340

Conditions

  • Advanced Platinum-resistant Ovarian Cancer
  • Advanced Platinum-resistant Fallopian Tube Cancer
  • Advanced Platinum-resistant Primary Peritoneal Cancer

Interventions

DrugSynonymsArms
REGN4018Monotherapy
cemiplimabREGN2810Combination Therapy

Purpose

The primary objectives of the Dose Escalation Phase are to assess the safety and pharmacokinetics (PK) in order to determine a maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of REGN4018 as monotherapy and in combination with cemiplimab. In the Dose Expansion Phase, the primary objectives are to assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as determined by the objective response rate (ORR). The secondary objectives of the Dose Escalation Phase are to assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as determined by ORR. In the Dose Expansion Phase, the secondary objectives are to characterize the safety profile in each expansion cohort and characterize the PK of REGN4018 as monotherapy and in combination with cemiplimab. In both the Dose Escalation and Dose Expansion Phases, secondary objectives are to assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR based on iRECIST, best overall response (BOR), duration of response (DOR), disease control rate, and progression-free survival (PFS) and to assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level.

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimental
  • REGN4018
Combination TherapyExperimental
  • REGN4018
  • cemiplimab

Eligibility Criteria

        Key Inclusion Criteria:

          1. Patients with histologically or cytologically confirmed diagnosis of advanced,
             epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian
             tube cancer who have all of the following:

               1. serum CA-125 level ≥2x upper limit of normal (ULN) (in screening)

               2. progression or relapse during or within 6 months of the most recent treatment
                  with a platinum-containing chemotherapy regimen

               3. documented progression on the most recent line of therapy

               4. no standard therapy options

          2. Adequate organ and bone marrow function

          3. Adequately controlled blood pressure

          4. Life expectancy of at least 3 months

        Key Exclusion Criteria:

          1. Recent treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy

          2. No more than 3 prior lines of cytotoxic chemotherapy for platinum-resistant disease

          3. Prior treatment with idelalisib (excluded from cemiplimab combination cohorts only)

          4. Prior treatment with a Mucin 16 (MUC16)-targeted therapy (excluded from expansion
             cohorts only)

          5. Untreated or active primary brain tumor, central nervous system (CNS) metastases, or
             spinal cord compression

          6. History of clinically significant cardiac disease

        Note: Other protocol Inclusion/Exclusion Criteria apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose-limiting toxicity (DLTs)
Time Frame:Up to 28 days
Safety Issue:
Description:Dose Escalation Phase

Secondary Outcome Measures

Measure:ORR based on RECIST 1.1 (Eisenhauer 2009)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation Phase
Measure:Number of participants with TEAEs (including immune-related)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of participants with SAEs
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of deaths
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Concentration in serum at end of infusion (Ceoi) of REGN4018 in monotherapy and in combination with cemiplimab during the dose expansion phase
Time Frame:Up to 62 weeks
Safety Issue:
Description:
Measure:Concentration in serum at pre-infusion (Ctrough) of REGN4018 in monotherapy and in combination with cemiplimab during the dose expansion phase.
Time Frame:Up to 62 weeks
Safety Issue:
Description:
Measure:ORR based on Immune-based therapy Response Evaluation Criteria in Solid Tumors (iRECIST) (Seymour 2017)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Best overall response (BOR)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Duration of response (DOR)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Disease control rate
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Progression-free survival (PFS) based on RECIST 1.1
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:PFS based on iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Cancer antigen-125 (CA-125) response
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

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