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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Cemiplimab; Drug: Sarilumab; Drug: REGN5678; Drug: REGN4336

Study type: Interventional

Funder types: Industry

Identifiers

NCT05125016

R4336-ONC-20104

2022-502130-17-00 (Other Identifier)

Details and patient eligibility

About

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)?

Enrollment: 370 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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370 participants in 3 patient groups

Module 1- Monotherapy

Experimental group

Description:

REGN4336

Treatment:

Drug: REGN4336

Drug: Sarilumab

Module 2-Combo Therapy

Experimental group

Description:

REGN4336 + Cemiplimab

Treatment:

Drug: REGN4336

Drug: Sarilumab

Drug: Cemiplimab

Module 3-Combo Therapy

Experimental group

Description:

REGN4336 + REGN5678

Treatment:

Drug: REGN5678

Drug: REGN4336

Drug: Sarilumab