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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

Phase 1/2 Study of REGN4336 (a PSMAxCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab or REGN5678 (a PSMAxCD28 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05125016
• Other study ID #: R4336-ONC-20104
• Secondary ID: 2022-502130-17-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 30, 2021
• Est. completion date: January 14, 2027

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 370
• Est. completion date: January 14, 2027
• Est. primary completion date: January 14, 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• REGN4336
Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion
• Cemiplimab
Administered concomitantly every 3 weeks (Q3W) by IV infusion
• REGN5678
Administered concomitantly QW by IV infusion
• Sarilumab
Administered once by IV infusion as prophylaxis prior to REGN4336 IV

Locations

Country	Name	City	State
United States	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Stanford Cancer Center	Palo Alto	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	University of Pennsylvania Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs)	Dose escalation	28 days, up to 42 days
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Dose escalation	Up to 5 years
Primary	Incidence and severity of Immune-mediated Adverse Events (imAEs)	Dose escalation	Up to 5 years
Primary	Incidence and severity of Serious Adverse Events (SAEs)	Dose escalation	Up to 5 years
Primary	Incidence and severity of adverse event of special interest (AESIs)	Dose escalation	Up to 5 years
Primary	Number of patients with grade =3 laboratory abnormalities	Dose escalation	Up to 5 years
Primary	REGN4336 monotherapy concentrations in serum	Dose escalation	Up to 5 years
Primary	REGN4336 concentrations in serum in combination with cemiplimab	Dose escalation	Up to 5 years
Primary	REGN4336 concentrations in serum in combination with REGN5678	Dose escalation	Up to 5 years
Primary	Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria	Dose expansion	Up to 5 years
Secondary	ORR per modified per modified PCWG3 criteria	Dose Escalation	Up to 5 years
Secondary	Incidence and severity of TEAEs	Dose expansion	Up to 5 years
Secondary	Incidence and severity of imAEs	Dose expansion	Up to 5 years
Secondary	Incidence and severity of SAEs	Dose expansion	Up to 5 years
Secondary	Incidence and severity of AESIs	Dose expansion	Up to 5 years
Secondary	Number of patients with grade =3 laboratory abnormalities	Dose expansion	Up to 5 years
Secondary	REGN4336 monotherapy concentrations in serum	Dose expansion	Up to 5 years
Secondary	REGN4336 concentrations in serum in combination with cemiplimab	Dose expansion	Up to 5 years
Secondary	REGN4336 concentrations in serum in combination with REGN5678	Dose expansion	Up to 5 years
Secondary	Percentage of patients with =50% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test =3 weeks later	Dose escalation and expansion	Up to 5 years
Secondary	Percentage of patients with =90% reduction in PSA from baseline, confirmed by a second PSA test =3 weeks later	Dose escalation and expansion	UP to 5 years
Secondary	Anti-drug antibodies (ADA) to REGN4336	Module 1	Up to 5 years
Secondary	ADA to REGN4336 and cemiplimab	Module 2	Up to 5 years
Secondary	ADA to REGN4336 and REGN5678	Module 3	Up to 5 years