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出境医 / 临床实验 / Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer

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

Study Description
Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: REGN5678 Drug: Cemiplimab Other: 18F-DCFPyL Phase 1 Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 129 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : June 16, 2024
Estimated Study Completion Date : June 16, 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Dose Escalation Cohorts
In 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.
 Drug: REGN5678
Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration once weekly (QW) to every three weeks (Q3W)

Drug: Cemiplimab
Administered at the assigned DL by intravenous (IV) infusion Q3W
Other Name: REGN2810

Other: 18F-DCFPyL
PSMA PET/CT imaging agent to be used at select sites
Experimental: Dose Expansion Cohorts
In a series of dose expansion cohorts, patients will receive combination therapy of REGN5678 at the recommended phase 2 dose (RP2D) and cemiplimab
 Drug: REGN5678
Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration once weekly (QW) to every three weeks (Q3W)

Drug: Cemiplimab
Administered at the assigned DL by intravenous (IV) infusion Q3W
Other Name: REGN2810

Other: 18F-DCFPyL
PSMA PET/CT imaging agent to be used at select sites
Outcome Measures
Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  2. Incidence and severity of adverse event of special interests (AESIs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  3. Incidence and severity of serious adverse events (SAEs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  4. Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  5. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: First dose through day 42 of last patient in each dose level ]
    Dose Escalation Phase

  6. Concentration of REGN5678 in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  7. Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  8. Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase


Secondary Outcome Measures :
  1. ORR per modified PCWG3 criteria [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase

  2. Incidence and severity of TEAEs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase

  3. Incidence and severity of AESIs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase

  4. Incidence and severity of SAEs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase

  5. Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase

  6. Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase

  7. ORR based upon prostate specific antigen (PSA) response [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases

  8. Percentage of patients with ≥90% decline of PSA [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases

  9. 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 ]
    Dose Escalation and Dose Expansion Phases

  10. 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 ]
    Dose Escalation and Dose Expansion Phases. Individual NRS used to rate the intensity of pain using a 0 to 10 numeric rating scale

  11. Presence or absence of antibodies against REGN5678 [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases

  12. Presence or absence of antibodies against cemiplimab [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

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

  • Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening

    ≥4 ng/mLthat has progressed within 6 months prior to screening as defined in the protocol

  • Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)

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, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) 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

Contacts and Locations

Contacts
Layout table for location contacts
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
Layout table for location information
United States, Colorado
Regeneron Study Site Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Regeneron Study Site Recruiting
Tampa, Florida, United States, 33612
United States, New York
Regeneron Study Site Recruiting
New York, New York, United States, 10029
Regeneron Study Site Recruiting
New York, New York, United States, 10032
United States, Oregon
Regeneron Study Site Recruiting
Portland, Oregon, United States, 97213
United States, Pennsylvania
Regeneron Study Site Recruiting
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Trials Management Regeneron Pharmaceuticals
Tracking Information
First Submitted Date  ICMJE May 30, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date March 10, 2021
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date June 16, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Incidence and severity of adverse event of special interests (AESIs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Incidence and severity of serious adverse events (SAEs) [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: First dose through day 42 of last patient in each dose level ]
    Dose Escalation Phase
  • Concentration of REGN5678 in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • ORR per modified PCWG3 criteria [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation Phase
  • Incidence and severity of TEAEs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
  • Incidence and severity of AESIs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
  • Incidence and severity of SAEs [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
  • Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
  • Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
    Dose Expansion Phase
  • ORR based upon prostate specific antigen (PSA) response [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases
  • Percentage of patients with ≥90% decline of PSA [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases
  • 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 ]
    Dose Escalation and Dose Expansion Phases
  • 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 ]
    Dose Escalation and Dose Expansion Phases. Individual NRS used to rate the intensity of pain using a 0 to 10 numeric rating scale
  • Presence or absence of antibodies against REGN5678 [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases
  • Presence or absence of antibodies against cemiplimab [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer
Official Title  ICMJE A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer
Brief Summary

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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration-resistant Prostate Cancer
Intervention  ICMJE
  • Drug: REGN5678
    Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration once weekly (QW) to every three weeks (Q3W)
  • Drug: Cemiplimab
    Administered at the assigned DL by intravenous (IV) infusion Q3W
    Other Name: REGN2810
  • Other: 18F-DCFPyL
    PSMA PET/CT imaging agent to be used at select sites
Study Arms  ICMJE
  • Experimental: Dose Escalation Cohorts
    In 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.
    Interventions:
    • Drug: REGN5678
    • Drug: Cemiplimab
    • Other: 18F-DCFPyL
  • Experimental: Dose Expansion Cohorts
    In a series of dose expansion cohorts, patients will receive combination therapy of REGN5678 at the recommended phase 2 dose (RP2D) and cemiplimab
    Interventions:
    • Drug: REGN5678
    • Drug: Cemiplimab
    • Other: 18F-DCFPyL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2021) 		129
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2019) 		123
Estimated Study Completion Date  ICMJE June 16, 2024
Estimated Primary Completion Date June 16, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

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

  • Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening

    ≥4 ng/mLthat has progressed within 6 months prior to screening as defined in the protocol

  • Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)

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, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03972657
Other Study ID Numbers  ICMJE R5678-ONC-1879
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
URL: https://vivli.org/
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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