REGN15505 (PSMAx4-1BB) Alone or in Combination With Cemiplimab or REGN4336 (PSMAxCD3) in Adult Patients With Metastatic Castration-Resistant Prostate Cancer and Clear Cell Renal Cell Carcinoma

Official title

Phase 1/2 Study of REGN15505 (a PSMAx4-1BB Bispecific Antibody) Administered Alone or in Combination With Cemiplimab or REGN4336 (a PSMAxCD3 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer and Clear Cell Renal Cell Carcinoma

Overview

This study is researching a new drug called REGN15505 when used alone or in combination with cemiplimab or in combination with REGN4336 in adult patients with mCRPC and ccRCC. The goal is to explore new ways to treat these cancers by helping immune cells target and destroy cancer cells. The study will evaluate the use of REGN15505 when administered alone, in combination with cemiplimab, or in combination with REGN4336 for: * Any side effects of study drugs * How well the study drugs work * How much REGN15505, cemiplimab, and REGN4336 are in the blood at different times * If the body makes antibodies to REGN15505 or REGN4336, which may mean the study drugs will not work as well as expected * What is the best dose of REGN15505 when administered alone and with cemiplimab and the best dose of REGN15505 and REGN4336 when used in combination

Interventions

• Drug REGN15505
  Administered per protocol
• Drug REGN15505+Cemiplimab
  Administered per protocol
• Drug REGN15505+REGN4336
  Administered per protocol

Primary outcome measures

• Occurrence of Dose Limiting Toxicities (DLTs) [Time frame: Up to 5 years]
• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to 5 years]
• Occurrence of Serious Adverse Events (SAEs) [Time frame: Up to 5 years]
• Occurrence of Adverse Events of Special Interest (AESIs) [Time frame: Up to 5 years]
• Composite Response (CompR) based on ≥50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic assessment of complete response (CR) or partial response (PR) [Time frame: Up to 5 years]
• Objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Time frame: Up to 5 years]

Secondary outcome measures (11)

• Occurrence of TEAEs [Time frame: Up to 5 years]
• Occurrence of SAEs [Time frame: Up to 5 years]
• Occurrence of AESIs [Time frame: Up to 5 years]
• CompR based on ≥50% decline of PSA from baseline and/or confirmed radiographic assessment of CR or PR [Time frame: Up to 5 years]
• Percentage of participants with ≥50% reduction of PSA [Time frame: Up to 5 years]
• Percentage of participants with ≥90% reduction in PSA [Time frame: Up to 5 years]
• Concentration of REGN15505 in serum [Time frame: Up to 5 years]
• Occurrence of Anti Drug Antibodies (ADA) against REGN15505 [Time frame: Up to 5 years]
• Occurrence of ADA against REGN4336 [Time frame: Up to 5 years]
• Magnitude of ADA against REGN15505 [Time frame: Up to 5 years]
• Magnitude of ADA against REGN4336 [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

Participants with mCRPC:

• Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
• mCRPC with PSA value at screening ≥4 ng/mL and that has progressed within 6 months prior to screening as described in the protocol
• Has received ≥2 lines of prior systemic therapy approved in the metastatic and/or castration-resistant setting as described in the protocol
• Have had either Orchiectomy or be on Luteinizing Hormone-Releasing Hormone (LHRH) agonist or antagonist therapy with serum testosterone <50 ng/dL AND agree to stay on LHRH agonist or antagonist therapy during the study

Participants with ccRCC:

• Men and women with histologically or cytologically confirmed Renal Cell Carcinoma (RCC) with a clear-cell component
• Diagnosis of metastatic ccRCC with at least 1 measurable lesion via Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
• Has progressed on or after ≥1 line of prior systemic therapy approved in the metastatic setting. Prior treatment must include an Anti Program Cell Death 1 (PD-1)/ Program Death Ligand 1 (PD-L1) therapy and either ipilimumab and/or a Tyrosine Kinase Inhibitor (TKI)

Exclusion criteria

For Both mCRPC and ccRCC Cohorts:

• Has received treatment with an approved systemic therapy (including sipuleucel-T for mCRPC patients) within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in the protocol

mCRPC Cohort Only:

• Has received prior Prostate Specific Membrane Antigen (PSMA)-targeting therapy with the exception of a PSMA-targeting radioligand (eg, 177Lu-PSMA-617)

Note: Other protocol defined inclusion/exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• City of Hope Phoenix — Goodyear
• City of Hope — Duarte
• City of Hope Chicago, City of Hope Cancer Center Chicago — Zion
• The University of Texas MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT07594106 · R15505-ONC-24144

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗