A Trial to Find Out if REGN5678 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

Metastatic Castration-resistant Prostate Cancer (mCRPC) Clinical Trial

Official title:

A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03972657
• Other study ID #: R5678-ONC-1879
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 12, 2019
• Est. completion date: July 3, 2026

Study information

• Verified date: March 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

The main purpose of this study is to determine the safety, tolerability (how your body reacts to the drug) and effectiveness (ability to treat your cancer) of REGN5678 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 345
• Est. completion date: July 3, 2026
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

mCRPC cohorts:

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

2. Prostate specific antigen (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. post-177Lu-PSMA-617 radiotherapy expansion cohort only. Must have received at least 2 doses of 177Lu-PSMA-617.

ccRCC cohorts:

1. Men and women with 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 approved radiopharmaceutical therapy (eg. 177Lu-PSMA-617) in mCRPC patients

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 describe 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

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma (ccRCC)
• Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• REGN5678
Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration
• Cemiplimab
Administered at the assigned DL by IV

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Montefiore Medical Center	New York	New York
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	Providence Cancer Institute Franz Clinic	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	The University of Arizona Cancer Center	Tucson	Arizona

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 and severity of treatment-emergent adverse events (TEAEs)	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Incidence and severity of adverse event of special interests (AESIs)	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Incidence and severity of serious adverse events (SAEs)	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Number of participants with Grade =3 laboratory abnormalities	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Incidence of dose-limiting toxicities (DLTs)	Dose Escalation Phase	First dose through day 42 of last participant in each dose level
Primary	Concentration of REGN5678 in serum over time	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Concentration of REGN5678 in combination with cemiplimab in serum over time	Dose Escalation Phase	Through study completion, Up to 5 years
Primary	Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria	Dose Expansion Phase - mCRPC cohort	Through study completion, Up to 5 years
Primary	ORR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria	Dose Expansion Phase - ccRCC cohort	Through study completion, Up to 5 years
Secondary	ORR per modified PCWG3 criteria	Dose Escalation Phase - mCRPC cohort	Through study completion, Up to 5 years
Secondary	ORR per RECIST 1.1 criteria	Dose Escalation Phase - ccRCC cohort	Through study completion, Up to 5 years
Secondary	Incidence and severity of TEAEs	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	Incidence and severity of AESIs	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	Incidence and severity of SAEs	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	Number of participants with grade =3 laboratory abnormalities	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	Concentration of REGN5678 in serum over time	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	Concentration of REGN5678 in combination with cemiplimab in serum over time	Dose Expansion Phase	Through study completion, Up to 5 years
Secondary	ORR based upon prostate specific antigen (PSA) response	Dose Escalation and Dose Expansion Phases - mCRPC cohorts	Through study completion, Up to 5 years
Secondary	Percentage of participants with =90% decline of PSA	Dose Escalation and Dose Expansion Phases- mCRPC cohorts	Through study completion, Up to 5 years
Secondary	Presence or absence of antibodies against REGN5678	Dose Escalation and Dose Expansion Phases	Through study completion, Up to 5 years
Secondary	Presence or absence of antibodies against cemiplimab	Dose Escalation and Dose Expansion Phases	Through study completion, Up to 5 years