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
Conditions
Metastatic Castration-resistant Prostate CancerDrugs
REGN4336, Cemiplimab, REGN5678, SarilumabSummary
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)?
Locations
10 locations Found with status Recruiting
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
Status
- RECRUITING
Central Contacts
- Clinical Trials Administrator
- 844-734-6643
- [email protected]
Study Director
- Clinical Trial Management
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
Study Plan
Module 1- Monotherapy
EXPERIMENTAL
REGN4336
DRUG:
REGN4336Description:
Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusionDRUG:
SarilumabDescription:
Administered once by IV infusion as prophylaxis prior to REGN4336 IV
Module 2-Combo Therapy
EXPERIMENTAL
REGN4336 + Cemiplimab
DRUG:
REGN4336Description:
Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusionDRUG:
CemiplimabDescription:
Administered concomitantly every 3 weeks (Q3W) by IV infusionDRUG:
SarilumabDescription:
Administered once by IV infusion as prophylaxis prior to REGN4336 IV
Module 3-Combo Therapy
EXPERIMENTAL
REGN4336 + REGN5678
DRUG:
REGN4336Description:
Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusionDRUG:
REGN5678Description:
Administered concomitantly QW by IV infusionDRUG:
SarilumabDescription:
Administered once by IV infusion as prophylaxis prior to REGN4336 IV
Outcome Measures
Primary Outcome Measures
Incidence of dose-limiting toxicities (DLTs)
Incidence and severity of treatment-emergent adverse events (TEAEs)
Incidence and severity of Immune-mediated Adverse Events (imAEs)
Incidence and severity of Serious Adverse Events (SAEs)
Incidence and severity of adverse event of special interest (AESIs)
Number of patients with grade u22653 laboratory abnormalities
REGN4336 monotherapy concentrations in serum
REGN4336 concentrations in serum in combination with cemiplimab
REGN4336 concentrations in serum in combination with REGN5678
Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
Secondary Outcome Measures
ORR per modified per modified PCWG3 criteria
Incidence and severity of TEAEs
Incidence and severity of imAEs
Incidence and severity of SAEs
Incidence and severity of AESIs
Number of patients with grade u22653 laboratory abnormalities
REGN4336 monotherapy concentrations in serum
REGN4336 concentrations in serum in combination with cemiplimab
REGN4336 concentrations in serum in combination with REGN5678
Percentage of patients with u226550% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test u22653 weeks later
Percentage of patients with u226590% reduction in PSA from baseline, confirmed by a second PSA test u22653 weeks later
Anti-drug antibodies (ADA) to REGN4336
ADA to REGN4336 and cemiplimab
ADA to REGN4336 and REGN5678
Timeline
Last Updated
February 7, 2024Start Date
November 18, 2021Today
February 5, 2025Completion Date ( Estimated )
January 14, 2027
Sponsors of this trial
Lead Sponsor
Regeneron Pharmaceuticals