A Trial to Find Out if REGN4336 is Safe and How Well it Works Alone and in Combination With Cemiplimab or REGN5678 for Adult Participants With Advanced Prostate Cancer

Clinicaltrials.gov ID: NCT05125016
db-list-check Status RECRUITING
b-loader Phase PHASE1, PHASE2
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 370

Conditions

Metastatic Castration-resistant Prostate Cancer

Drugs

REGN4336, Cemiplimab, REGN5678, Sarilumab

Summary

This study is researching an investigational drug called REGN4336. Some participants may receive additional investigational drugs in combination with REGN4336. These additional drugs include REGN5678, cemiplimab and sarilumab.The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug) and effectiveness of REGN4336 alone, in combination with cemiplimab, or in combination with REGN5678. REGN4336, cemiplimab and REGN5678 are a type of treatment for cancer called immunotherapy,and are intended to activate T-cells to attack cancer cells.This study has 2 parts. The purpose of Part 1 is to determine a safe dose of REGN4336 when given alone or when given in combination with cemiplimab or REGN5678. The purpose of Part 2 is to use the REGN4336 dose(s) determined in Part 1 to further test how well REGN4336 works to shrink tumors either when given alone or in combination with cemiplimab or REGN5678.This study is looking at several other research questions, including:* What side effects may happen from taking REGN4336 alone, in combination with cemiplimab, or in combination with REGN5678? * How much REGN4336 is in the blood at different times when it is given alone, in combination with cemiplimab, or in combination with REGN5678? * Does the body make antibodies against the study drugs (REGN4336, cemiplimab, or REGN5678)?

Locations

10 locations Found with status Recruiting

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Status

  • RECRUITING

Central Contacts

Study Director

  • Clinical Trial Management

Eligibility Criteria

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, according to 1 of the following:

1. PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment
2. Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression
3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression NOTE: Measurable disease per RECIST version 1.1 per local reading at screening is not an eligibility criterion for enrollment
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 or immune-modulating therapy (except for Sipuleucel-T) within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior PSMA-targeting therapy. Exception: Prior therapy with approved PSMA-targeted radioligand(s) is permitted
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, as described in the protocol.

NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Study Plan

Module 1- Monotherapy

EXPERIMENTAL

REGN4336

  • DRUG:

    REGN4336

    Description:

    Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion
  • DRUG:

    Sarilumab

    Description:

    Administered once by IV infusion as prophylaxis prior to REGN4336 IV

Module 2-Combo Therapy

EXPERIMENTAL

REGN4336 + Cemiplimab

  • DRUG:

    REGN4336

    Description:

    Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion
  • DRUG:

    Cemiplimab

    Description:

    Administered concomitantly every 3 weeks (Q3W) by IV infusion
  • DRUG:

    Sarilumab

    Description:

    Administered once by IV infusion as prophylaxis prior to REGN4336 IV

Module 3-Combo Therapy

EXPERIMENTAL

REGN4336 + REGN5678

  • DRUG:

    REGN4336

    Description:

    Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion
  • DRUG:

    REGN5678

    Description:

    Administered concomitantly QW by IV infusion
  • DRUG:

    Sarilumab

    Description:

    Administered once by IV infusion as prophylaxis prior to REGN4336 IV

Outcome Measures

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs)

Time Frame: 28 days, up to 42 days

Incidence and severity of treatment-emergent adverse events (TEAEs)

Time Frame: Up to 5 years

Incidence and severity of Immune-mediated Adverse Events (imAEs)

Time Frame: Up to 5 years

Incidence and severity of Serious Adverse Events (SAEs)

Time Frame: Up to 5 years

Incidence and severity of adverse event of special interest (AESIs)

Time Frame: Up to 5 years

Number of patients with grade u22653 laboratory abnormalities

Time Frame: Up to 5 years

REGN4336 monotherapy concentrations in serum

Time Frame: Up to 5 years

REGN4336 concentrations in serum in combination with cemiplimab

Time Frame: Up to 5 years

REGN4336 concentrations in serum in combination with REGN5678

Time Frame: Up to 5 years

Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria

Time Frame: Up to 5 years

Secondary Outcome Measures

ORR per modified per modified PCWG3 criteria

Time Frame: Up to 5 years

Incidence and severity of TEAEs

Time Frame: Up to 5 years

Incidence and severity of imAEs

Time Frame: Up to 5 years

Incidence and severity of SAEs

Time Frame: Up to 5 years

Incidence and severity of AESIs

Time Frame: Up to 5 years

Number of patients with grade u22653 laboratory abnormalities

Time Frame: Up to 5 years

REGN4336 monotherapy concentrations in serum

Time Frame: Up to 5 years

REGN4336 concentrations in serum in combination with cemiplimab

Time Frame: Up to 5 years

REGN4336 concentrations in serum in combination with REGN5678

Time Frame: Up to 5 years

Percentage of patients with u226550% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test u22653 weeks later

Time Frame: Up to 5 years

Percentage of patients with u226590% reduction in PSA from baseline, confirmed by a second PSA test u22653 weeks later

Time Frame: UP to 5 years

Anti-drug antibodies (ADA) to REGN4336

Time Frame: Up to 5 years

ADA to REGN4336 and cemiplimab

Time Frame: Up to 5 years

ADA to REGN4336 and REGN5678

Time Frame: Up to 5 years

Timeline

  • Last Updated
    February 7, 2024
  • Start Date
    November 18, 2021
  • Today
    January 16, 2025
  • Completion Date ( Estimated )
    January 14, 2027

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