Clinical trial NCT05125016: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-18
Enrollment: 370
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study contains 3 separate modules in parallel: monotherapy with REGN4336 (Module 1) and combination therapies: REGN4336 plus cemiplimab (Module 2) and REGN4336 plus REGN5678 (Module 3). All 3 modules contain independent dose escalation cohorts and up to 2 recommended phase 2 dose regimens during dose expansion.
Primary purpose: TREATMENT

Brief 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)?


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 28 days, up to 42 days
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 5 years
measure: Incidence and severity of Immune-mediated Adverse Events (imAEs)
timeFrame: Up to 5 years
measure: Incidence and severity of Serious Adverse Events (SAEs)
timeFrame: Up to 5 years
measure: Incidence and severity of adverse event of special interest (AESIs)
timeFrame: Up to 5 years
measure: Number of patients with grade ≥3 laboratory abnormalities
timeFrame: Up to 5 years
measure: REGN4336 monotherapy concentrations in serum
timeFrame: Up to 5 years
measure: REGN4336 concentrations in serum in combination with cemiplimab
timeFrame: Up to 5 years
measure: REGN4336 concentrations in serum in combination with REGN5678
timeFrame: Up to 5 years
measure: Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
timeFrame: Up to 5 years
Secondary outcomes:
measure: ORR per modified per modified PCWG3 criteria
timeFrame: Up to 5 years
measure: Incidence and severity of TEAEs
timeFrame: Up to 5 years
measure: Incidence and severity of imAEs
timeFrame: Up to 5 years
measure: Incidence and severity of SAEs
timeFrame: Up to 5 years
measure: Incidence and severity of AESIs
timeFrame: Up to 5 years
measure: Number of patients with grade ≥3 laboratory abnormalities
timeFrame: Up to 5 years
measure: REGN4336 monotherapy concentrations in serum
timeFrame: Up to 5 years
measure: REGN4336 concentrations in serum in combination with cemiplimab
timeFrame: Up to 5 years
measure: REGN4336 concentrations in serum in combination with REGN5678
timeFrame: Up to 5 years
measure: Percentage of patients with ≥50% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥3 weeks later
timeFrame: Up to 5 years
measure: Percentage of patients with ≥90% reduction in PSA from baseline, confirmed by a second PSA test ≥3 weeks later
timeFrame: UP to 5 years
measure: Anti-drug antibodies (ADA) to REGN4336
timeFrame: Up to 5 years
measure: ADA to REGN4336 and cemiplimab
timeFrame: Up to 5 years
measure: ADA to REGN4336 and REGN5678
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center - Blake Wilbur Drive
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University James Cancer Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine University of Pennsylvania Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: