REGN4336 (a PSMAXCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Adult Male Patients With Metastatic Castration-Resistant Prostate Cancer

Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05125016
Collaborator
(none)
199
7
2
56.1
28.4
0.5

Study Details

Study Description

Brief Summary

The primary objective of the study is:
Dose Escalation:

• To assess the safety, tolerability, and pharmacokinetics (PK) and to determine recommended phase 2 dosing regimen (RP2DR) of REGN4336 separately as monotherapy or in combination with cemiplimab

Dose Expansion:

• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by objective response rate (ORR) per modified Prostate Cancer Working Group (PCWG3) criteria

The secondary objectives of the study are:
Dose Escalation:

• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by ORR per modified PCWG3 criteria

Dose Expansion:
  • To characterize the safety profile in each expansion cohort

  • To characterize the PK of REGN4336 as monotherapy or in combination with cemiplimab

In both Dose Escalation and Dose Expansion:
  • To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by prostate specific antigen (PSA) decline

  • To evaluate immunogenicity of REGN4336 in Module 1 and immunogenicity of REGN4336 and cemiplimab in Module 2

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
199 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The study contains 2 separate modules in parallel: monotherapy with REGN4336 (Module 1) and combination therapy with REGN4336 and cemiplimab (Module 2). Both modules contain independent dose escalation cohorts and up to 2 recommended phase 2 dose regimens during dose expansion.The study contains 2 separate modules in parallel: monotherapy with REGN4336 (Module 1) and combination therapy with REGN4336 and cemiplimab (Module 2). Both modules contain independent dose escalation cohorts and up to 2 recommended phase 2 dose regimens during dose expansion.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 Study of REGN4336 (a PSMAXCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date :
Nov 30, 2021
Anticipated Primary Completion Date :
Aug 4, 2026
Anticipated Study Completion Date :
Aug 4, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Module 1- Monotherapy

REGN4336

Drug: REGN4336
Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.

Other: 18F-DCFPyL
Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites

Experimental: Module 2-Combo Therapy

REGN4336 + Cemiplimab

Drug: REGN4336
Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.

Drug: Cemiplimab
Administered concomitantly every 3 weeks (Q3W) by IV infusion
Other Names:
  • REGN2810
  • Libtayo
  • Other: 18F-DCFPyL
    Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of dose-limiting toxicities (DLTs) [28 days, up to 42 days]

      Dose escalation

    2. Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 5 years]

      Dose escalation

    3. Incidence and severity of Immune-related Adverse Events (irAEs) [Up to 5 years]

      Dose escalation

    4. Incidence and severity of SAEs [Up to 5 years]

      Dose escalation

    5. Incidence and severity of adverse event of special interests (AESIs) [Up to 5 years]

      Dose escalation

    6. Number of patients with grade ≥3 laboratory abnormalities [Up to 5 years]

      Dose escalation

    7. REGN4336 concentrations in serum [Up to 5 years]

      Dose escalation: As monotherapy or in combination with cemiplimab

    8. ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria [Up to 5 years]

      Dose expansion

    Secondary Outcome Measures

    1. ORR per modified per modified PCWG3 criteria [Up to 5 years]

      Dose Escalation:

    2. Incidence of dose-limiting toxicities (DLTs) [Up to 28 days]

      Dose expansion

    3. Incidence and severity of TEAEs [Up to 5 years]

      Dose expansion

    4. Incidence and severity of Immune-related Adverse Events [Up to 5 years]

      Dose expansion

    5. Incidence and severity of SAEs [Up to 5 years]

      Dose expansion

    6. Incidence and severity of adverse event of special interests (AESIs) [Up to 5 years]

      Dose expansion

    7. Number of patients with grade ≥3 laboratory abnormalities [Up to 5 years]

      Dose expansion

    8. REGN4336 concentrations in serum [Up to 5 years]

      Dose expansion: As monotherapy or in combination with cemiplimab

    9. Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [Up to 5 years]

      Dose escalation and expansion

    10. Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [UP to 5 years]

      Dose escalation and expansion

    11. Anti-drug antibodies (ADA) to REGN4336 [Up to 5 years]

      Module 1

    12. ADA to REGN4336 and cemiplimab [Up to 5 years]

      Module 2

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    1. Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma

    2. Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol

    3. Has progressed upon or intolerant to ≥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 (e.g. abiraterone, enzalutamide, apalutamide, or darolutamide)

    Key Exclusion Criteria:
    1. 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

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

    3. Has received prior PSMA-targeting therapy

    4. 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

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

    6. 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

    7. 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

    Locations

    Site City State Country Postal Code
    1 Stanford Cancer Center Palo Alto California United States 94304
    2 Norton Cancer Institute Louisville Kentucky United States 40207
    3 University of Maryland, Greenebaum Comprehensive Cancer Center Baltimore Maryland United States 21201
    4 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    5 University of Pennsylvania Perelman Center for Advanced Medicine Philadelphia Pennsylvania United States 19104
    6 Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization Philadelphia Pennsylvania United States 19107
    7 Froedtert and Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Regeneron Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT05125016
    Other Study ID Numbers:
    • R4336-ONC-20104
    • 2021-001104-15
    First Posted:
    Nov 18, 2021
    Last Update Posted:
    Aug 5, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Regeneron Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 5, 2022