Clinical trial NCT03972657: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC)
Clear Cell Renal Cell Carcinoma (ccRCC)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 345
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, Up to 5 years
measure: Incidence and severity of adverse event of special interests (AESIs)
timeFrame: Through study completion, Up to 5 years
measure: Incidence and severity of serious adverse events (SAEs)
timeFrame: Through study completion, Up to 5 years
measure: Number of participants with Grade ≥3 laboratory abnormalities
timeFrame: Through study completion, Up to 5 years
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: First dose through day 42 of last participant in each dose level
measure: Concentration of REGN5678 in serum over time
timeFrame: Through study completion, Up to 5 years
measure: Concentration of REGN5678 in combination with cemiplimab in serum over time
timeFrame: Through study completion, Up to 5 years
measure: Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria
timeFrame: Through study completion, Up to 5 years
measure: ORR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
timeFrame: Through study completion, Up to 5 years
Secondary outcomes:
measure: ORR per modified PCWG3 criteria
timeFrame: Through study completion, Up to 5 years
measure: ORR per RECIST 1.1 criteria
timeFrame: Through study completion, Up to 5 years
measure: Incidence and severity of TEAEs
timeFrame: Through study completion, Up to 5 years
measure: Incidence and severity of AESIs
timeFrame: Through study completion, Up to 5 years
measure: Incidence and severity of SAEs
timeFrame: Through study completion, Up to 5 years
measure: Number of participants with grade ≥3 laboratory abnormalities
timeFrame: Through study completion, Up to 5 years
measure: Concentration of REGN5678 in serum over time
timeFrame: Through study completion, Up to 5 years
measure: Concentration of REGN5678 in combination with cemiplimab in serum over time
timeFrame: Through study completion, Up to 5 years
measure: ORR based upon prostate specific antigen (PSA) response
timeFrame: Through study completion, Up to 5 years
measure: Percentage of participants with ≥90% decline of PSA
timeFrame: Through study completion, Up to 5 years
measure: Presence or absence of antibodies against REGN5678
timeFrame: Through study completion, Up to 5 years
measure: Presence or absence of antibodies against cemiplimab
timeFrame: Through study completion, Up to 5 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute (JWCI)
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute (SCRI)
state: Colorado
city: New Haven
country: United States
facility: Yale University Hospital
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center - McKinley Drive
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Health Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University - The Trustees of Columbia University in the City of New York
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University (3485 S. Bond)
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: Emily Couric Clinical Cancer Center
state: Virginia
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trials Management
role: STUDY_DIRECTOR
References: