Clinical Trials /

Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.

NCT04590326

Description:

The primary objectives of the study are: In the Dose Escalation Phase: - To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or REGN4018, in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations In the Dose Expansion Phase: - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 The secondary objectives of the study are: In the Dose Escalation Phase: - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1 In the Dose Expansion Phase: - To characterize the safety profile in each expansion cohort - To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) In both the Dose Escalation and Dose Expansion Phases: - To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST - To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) - Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018

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 REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.
  • Official Title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)

Clinical Trial IDs

  • ORG STUDY ID: R5668-ONC-1938
  • SECONDARY ID: 2020-000063-23
  • NCT ID: NCT04590326

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer

Interventions

DrugSynonymsArms
REGN5668Module 1
CemiplimabREGN2810, LibtayoModule 1
REGN4018Module 2

Purpose

The primary objectives of the study are: In the Dose Escalation Phase: - To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or REGN4018, in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations In the Dose Expansion Phase: - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 The secondary objectives of the study are: In the Dose Escalation Phase: - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1 In the Dose Expansion Phase: - To characterize the safety profile in each expansion cohort - To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) In both the Dose Escalation and Dose Expansion Phases: - To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST - To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) - Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018

Trial Arms

NameTypeDescriptionInterventions
Module 1ExperimentalREGN5668 and cemiplimab
  • REGN5668
  • Cemiplimab
Module 2ExperimentalREGN5668 and REGN4018
  • REGN5668
  • REGN4018

Eligibility Criteria

        Key Inclusion Criteria:

          1. Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian
             cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has
             received at least 1 line of platinum-based systemic therapy as defined in the protocol

          2. In dose escalation, patients will provide either newly obtained biopsy (newly obtained
             biopsies at screening are required unless medically inappropriate and discussed with
             medical monitor) or archived tumor tissue. In expansion, patients will provide a fresh
             tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients
             who (in the opinion of the investigator) have accessible lesions that can be biopsied
             without significant risk to the patient are eligible.

          3. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor
             lesions in a previously irradiated area are considered measurable if progression has
             been demonstrated in such lesions after radiation.

          4. Has a serum CA-125 level ≥2x ULN (in screening)

          5. Has adequate organ and bone marrow function as defined in the protocol

          6. Has a life expectancy of at least 3 months

        Key Exclusion Criteria:

          1. Has participated in a study of an investigational agent (except biologics and/or
             immunotherapy) or an investigational device within 4 weeks of first dose of study drug

          2. Has received treatment with an approved systemic therapy (except biologics and/or
             immunotherapy) within 3 weeks or has not yet recovered as defined in the protocol

          3. Prior anti-cancer immunotherapy as defined in the protocol

          4. Has received radiation therapy or major surgery within 14 days of first administration
             of study drug as defined in the protocol

          5. Has had another malignancy within the last 5 years that is progressing, requires
             active treatment, or has a high likelihood of recurrence as defined in the protocol

          6. Expansion cohorts only: Prior treatment with a MUC16-targeted therapy

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

          8. Has any condition that requires ongoing/continuous corticosteroid therapy as defined
             in the protocol within 1 week prior to the first dose of study drug

          9. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that
             required treatment with systemic immunosuppressive treatments as defined in the
             protocol

         10. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease,
             or spinal cord compression as defined in the protocol

         11. Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or
             uncontrolled seizures in the year prior to first dose of study drug

         12. Has history of clinically significant cardiovascular disease as defined in the
             protocol

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

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLT)
Time Frame:42 days
Safety Issue:
Description:Dose escalation phase, Module 1

Secondary Outcome Measures

Measure:Concentration of REGN4018 in serum over time
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose expansion phase
Measure:Concentration of cemiplimab in serum over time
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose expansion phase
Measure:ORR based on iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:BOR based on RECIST 1.1 and iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:DOR based on RECIST 1.1 and iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:DCR based on RECIST 1.1 and iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:PFS based on RECIST 1.1 and iRECIST
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination)
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:Presence or absence of anti-drug antibodies against REGN5668
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:Presence or absence of anti-drug antibodies against REGN4018
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases
Measure:Presence or absence of anti-drug antibodies against cemiplimab
Time Frame:Up to 62 weeks
Safety Issue:
Description:Dose escalation and expansion phases

Details

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

Trial Keywords

  • Progressive
  • Recurrent
  • Refractory
  • Serum CA-125 levels >2x ULN

Last Updated

January 22, 2021