A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); Clear Cell Renal Cell Carcinoma (ccRCC)

Treatments: Drug: REGN5678; Drug: Cemiplimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03972657

R5678-ONC-1879

Details and patient eligibility

About

The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug[s]) and effectiveness (ability to treat the cancer) of REGN5678 (Nezastomig) alone, or in combination with cemiplimab.

The study has 2 parts. The goal of Part 1 (dose escalation) is to determine a safe dose(s) of REGN5678 when it is given alone or in combination with cemiplimab. The goal of Part 2 (dose expansion) is to use the REGN5678 drug dose(s) found in Part 1 to see how well REGN5678 alone or in combination with cemiplimab works to shrink tumors.

This study is looking at several other research questions, including:

1. Side effects that may be experienced by taking REGN5678 alone or in combination with cemiplimab
2. How REGN5678 alone or in combination with cemiplimab works in the body
3. How much REGN5678 and/or cemiplimab are present in the blood
4. To see if REGN5678 alone or in combination with cemiplimab works to reduce the size of the tumor by helping the immune system destroy the tumor

Enrollment: 345 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

mCRPC cohorts (men):

1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.

2. PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.

3. 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:

   1. one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
   2. 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol

ccRCC cohorts (men and women):

1. Histologically or cytologically confirmed RCC with a clear-cell component.
2. Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
3. Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-Programmed Death-1 (receptor) [PD-1]/Programmed Death-Ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor

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, as described in the protocol
2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior PSMA-targeting therapy with the exception of a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC
4. Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
5. Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as described in the protocol
6. 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
7. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, as described in the protocol
8. 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
9. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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345 participants in 4 patient groups

mCRPC - dose escalation cohort

Experimental group

Description:

REGN5678 with or without cemiplimab

Treatment:

Drug: Cemiplimab

Drug: REGN5678

mCRPC - dose expansion cohort

Experimental group

Description:

REGN5678 with or without cemiplimab

Treatment:

Drug: REGN5678

ccRCC - dose escalation cohort

Experimental group

Description:

REGN5678 with or without cemiplimab

Treatment:

Drug: Cemiplimab

Drug: REGN5678

ccRCC - dose expansion cohort

Experimental group

Description:

REGN5678 with or without cemiplimab

Treatment:

Drug: REGN5678