Clinical Trials /

Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer

NCT03972657

Description:

The primary objectives of the study in Dose Escalation are to evaluate safety, tolerability, and pharmacokinetics (PK) of REGN5678 alone and in combination with cemiplimab and in Dose Expansion are to assess efficacy, as measured by objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria, of REGN5678 in combination with cemiplimab. The secondary objectives of the study in Dose Escalation are to assess efficacy, as measured by ORR per modified PCWG3 criteria, of REGN5678 in combination with cemiplimab and in Dose Expansion are to characterize the safety profile in each expansion cohort and to characterize the PK of REGN5678 in combination with cemiplimab. Secondary objectives in both Dose Escalation and Dose Expansion are to assess efficacy of REGN5678 in combination with cemiplimab, as measured by additional criteria and to assess immunogenicity of REGN5678 in combination with cemiplimab.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer
  • Official Title: A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: R5678-ONC-1879
  • NCT ID: NCT03972657

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
REGN5678Dose Escalation Cohorts
CemiplimabREGN2810Dose Escalation Cohorts

Purpose

The primary objectives of the study in Dose Escalation are to evaluate safety, tolerability, and pharmacokinetics (PK) of REGN5678 alone and in combination with cemiplimab and in Dose Expansion are to assess efficacy, as measured by objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria, of REGN5678 in combination with cemiplimab. The secondary objectives of the study in Dose Escalation are to assess efficacy, as measured by ORR per modified PCWG3 criteria, of REGN5678 in combination with cemiplimab and in Dose Expansion are to characterize the safety profile in each expansion cohort and to characterize the PK of REGN5678 in combination with cemiplimab. Secondary objectives in both Dose Escalation and Dose Expansion are to assess efficacy of REGN5678 in combination with cemiplimab, as measured by additional criteria and to assess immunogenicity of REGN5678 in combination with cemiplimab.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation CohortsExperimentalIn a series of dose escalation cohorts, patients will receive a 3-week monotherapy lead-in of 3 weekly doses of REGN5678 followed by REGN5678 and cemiplimab in combination.
  • REGN5678
  • Cemiplimab
Dose Expansion CohortsExperimentalIn a series of dose expansion cohorts, patients will receive combination therapy of REGN5678 at the recommended phase 2 dose (RP2D) and cemiplimab
  • REGN5678
  • Cemiplimab

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without pure
             small cell carcinoma

          -  Metastatic, castration-resistant prostate cancer (mCRPC) that has progressed within 6
             months prior to screening

          -  Has received ≥2 lines of approved systemic therapy for mCRPC, including a second
             -generation hormonal agent

          -  Adequate organ and bone marrow function

        Key Exclusion Criteria:

          -  Has received treatment with an approved systemic therapy within 3 weeks of dosing or
             has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities

          -  Has received any previous systemic biologic therapy within 5 half-lives of first dose
             of study therapy

          -  Has received prior PSMA-targeting therapy

          -  Dose Expansion Only: Has had prior anti-cancer immunotherapy

          -  Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg
             prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose
             of study therapy

          -  Ongoing or recent (within 5 years) evidence of significant autoimmune disease that
             required treatment with systemic immunosuppressive treatments

          -  Encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or
             uncontrolled seizures in the year prior to first dose of study therapy

          -  Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or
             hepatitis C infection; or diagnosis of immunodeficiency

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

Primary Outcome Measures

Measure:Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation Phase

Secondary Outcome Measures

Measure:ORR per modified PCWG3 criteria
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation Phase
Measure:Incidence and severity of TEAEs
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Expansion Phase
Measure:Incidence and severity of AESIs
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Expansion Phase
Measure:Incidence and severity of SAEs
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Expansion Phase
Measure:Number of patients with grade ≥3 laboratory abnormalities
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Expansion Phase
Measure:Concentration of REGN5678 in combination with cemiplimab in serum over time
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Expansion Phase
Measure:ORR based upon prostate specific antigen (PSA) response
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Percentage of patients with ≥90% decline of PSA
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Percentage of patients who have achieved conversion of circulating tumor cell (CTC) count from baseline of ≥5 cells/7.5mL to <5 cells/7.5mL
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Percentage of patients who have achieved an absolute improvement in pain on an 11-point Numeric Pain Rating Scale (NRS) without an overall increase in opiate use
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases. Individual NRS used to rate the intensity of pain using a 0 to 10 numeric rating scale
Measure:Presence or absence of antibodies against REGN5678
Time Frame:Through study completion, Up to 5 years
Safety Issue:
Description:Dose Escalation and Dose Expansion Phases
Measure:Presence or absence of antibodies against cemiplimab
Time Frame:Through study completion, Up to 5 years
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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