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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Metastatic Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: REGN4336
* Drug: Cemiplimab
* Other: 18F-DCFPyL


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma 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 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: 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 Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy Has received prior PSMA-targeting therapy 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 Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module 1- Monotherapy<br>REGN4336 | Drug: REGN4336<br>* Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.<br>Other: 18F-DCFPyL<br>* Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites<br>|
| Experimental: Module 2-Combo Therapy<br>REGN4336 + Cemiplimab | Drug: REGN4336<br>* Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.<br>Drug: Cemiplimab<br>* Administered concomitantly every 3 weeks (Q3W) by IV infusion<br>* Other names: Libtayo;Other: 18F-DCFPyL<br>* Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) | Dose escalation | 28 days, up to 42 days | 
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Dose escalation | Up to 5 years | 
| Incidence and severity of Immune-mediated Adverse Events (imAEs) | Dose escalation | Up to 5 years | 
| Incidence and severity of SAEs | Dose escalation | Up to 5 years | 
| Incidence and severity of adverse event of special interests (AESIs) | Dose escalation | Up to 5 years | 
| Number of patients with grade ≥3 laboratory abnormalities | Dose escalation | Up to 5 years | 
| REGN4336 concentrations in serum | Dose escalation: As monotherapy or in combination with cemiplimab | Up to 5 years | 
| ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria | Dose expansion | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR per modified per modified PCWG3 criteria | Dose Escalation: | Up to 5 years | 
| Incidence of dose-limiting toxicities (DLTs) | Dose expansion | Up to 28 days | 
| Incidence and severity of TEAEs | Dose expansion | Up to 5 years | 
| Incidence and severity of Immune-mediated Adverse Events | Dose expansion | Up to 5 years | 
| Incidence and severity of SAEs | Dose expansion | Up to 5 years | 
| Incidence and severity of adverse event of special interests (AESIs) | Dose expansion | Up to 5 years | 
| Number of patients with grade ≥3 laboratory abnormalities | Dose expansion | Up to 5 years | 
| REGN4336 concentrations in serum | Dose expansion: As monotherapy or in combination with cemiplimab | Up to 5 years | 
| Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later | Dose escalation and expansion | Up to 5 years | 
| Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later | Dose escalation and expansion | UP to 5 years | 
| Anti-drug antibodies (ADA) to REGN4336 | Module 1 | Up to 5 years | 
| ADA to REGN4336 and cemiplimab | Module 2 | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)