Clinical Trials /

Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Recurrent 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) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 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 by RECIST 1.1. 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 immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate, complete response (CR) rate and progression-free survival (PFS) based on RECIST 1.1 and iRECIST, to assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level and immunogenicity of REGN4018 and cemiplimab.

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

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03564340

Trial Eligibility

Document

Title

  • Brief Title: Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer
  • Official Title: A Phase 1/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: R4018-ONC-1721
  • SECONDARY ID: 2019-003298-24
  • NCT ID: NCT03564340

Conditions

  • Recurrent Ovarian Cancer
  • Recurrent Fallopian Tube Cancer
  • Recurrent Primary Peritoneal Cancer

Interventions

DrugSynonymsArms
REGN4018Combination Therapy
cemiplimabREGN2810, LibtayoCombination 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) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 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 by RECIST 1.1. 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 immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate, complete response (CR) rate and progression-free survival (PFS) based on RECIST 1.1 and iRECIST, to assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level and immunogenicity of REGN4018 and cemiplimab.

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimentalREGN4018 administration
  • REGN4018
Combination TherapyExperimentalREGN4018 and cemiplimab administration
  • REGN4018
  • cemiplimab

Eligibility Criteria

        Key Inclusion Criteria:

          -  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:

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

          -  has received at least 1 line of platinum-containing therapy or must be
             platinum-intolerant

          -  documented relapse or progression on or after the most recent line of therapy

          -  no standard therapy options likely to convey clinical benefit

          -  Adequate organ and bone marrow function as defined in the protocol

          -  Adequately controlled blood pressure

          -  Life expectancy of at least 3 months

        Key Exclusion Criteria:

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

          -  Expansion cohort only: More than 3 prior lines of cytotoxic chemotherapy for
             platinum-experienced and/or intolerant disease

          -  Expansion cohort only: prior treatment with a Mucin 16 (MUC16)-targeted therapy

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

          -  History of clinically significant cardiac disease, myocarditis, presence of moderate
             to large pericardial effusion and other measures of cardiac health as defined in the
             protocol

          -  Moderate to large pleural effusion as defined in the protocol

        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) for REGN4018 monotherapy
Time Frame:Up to 28 days
Safety Issue:
Description:Dose Escalation Phase

Secondary Outcome Measures

Measure:ORR based on RECIST 1.1 (Eisenhauer 2009) for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation Phase
Measure:ORR based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation Phase
Measure:Number of participants with TEAEs (including irAEs) for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of participants with SAEs for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of participants with SAEs for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of deaths for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of deaths for REGN4018 with cemiplimab
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) for REGN4018 monotherapy
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) for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Concentration of REGN4018 in serum over time for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Expansion Phase
Measure:ORR based on iRECIST (Seymour 2017) for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:ORR based on iRECIST for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:BOR based on iRECIST for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:BOR based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:BOR based on iRECIST for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:DOR based on iRECIST for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:DOR based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:DOR based on iRECIST for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Disease control rate based on RECIST 1.1 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Disease control rate based on iRECIST for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Disease control rate based on iRECIST for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:CR rate based on iRECIST 1.1 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:CR rate based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab
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 for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:PFS based on iRECIST for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:PFS based on RECIST 1.1 for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:PFS based on iRECIST for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Cancer antigen-125 (CA-125) response for REGN4018 monotherapy
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:CA-125 response for REGN4018 with cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Presence or absence of anti-drug antibodies against REGN4018
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Presence or absence of anti-drug antibodies against cemiplimab
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

Last Updated

January 29, 2021