Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Treatment-experienced metastatic Castration-Resistant Prostate Cancer (mCRPC)
Brief summary
This study is researching an investigational drug called REGN4336 both alone or together with another investigational drug called REGN5678. The study is focused on participants with previously treated metastatic prostate cancer. The main purpose of the study is to look at the safety, tolerability (how the body reacts to the drug) and effectiveness (how well the drug works to shrink tumors) of REGN4336 when given in combination with REGN5678. The study has 2 parts. The purpose of Part 1 is to determine a safe dose(s) of REGN4336 to be given alone or in combination with REGN5678. Part 1 is known as the "dose escalation" phase. The purpose of Part 2, (known as the "dose expansion" phase), is to use the doses of REGN4336 and REGN5678 selected in Part 1 to further test how well the combination treatment with REGN4336 and REGN5678 works to shrink tumors. The study is looking at several other research questions, including: * What side effects may happen from taking REGN4336 alone or in combination with REGN5678 * How well does REGN4336 in combination with REGN5678 reduce tumor size * How much REGN4336 is in the blood at different times when it is given alone or in combination with REGN5678 * Does the body make antibodies against the study drugs (REGN4336 or REGN5678)
Interventions
DRUGREGN4336
Administered per the protocol
DRUGREGN5678
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Note: Prior to the current protocol amendment (PA), a Module to evaluate REGN4336 in combination with cemiplimab was included in the study design (Module 2). This Module was de-prioritized in this PA and removed. No patients were dosed in Module 2
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 and that has progressed within 6 months prior to screening, according to at least 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 biologic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in inclusion criteria 2. Has received any previous systemic biologic or anti-cancer immunotherapy within 5 half-lives of first dose of study therapy, as described in the protocol 3. Has received prior Prostate-Specific Membrane Antigen (PSMA)-targeting therapy NOTE: Prior therapy with PSMA-targeting radioligand(s) (eg, 177Lu-PSMA-617) is permitted. However, a period of 12 weeks must elapse between the last dose of the PSMA- targeting radioligand and the first dose of study drug 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 Virus (HBV), or Hepatitis C Virus (HCV) infection; or diagnosis of immunodeficiency, as described in the protocol. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | up to 21 days | Dose escalation |
| Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) | Up to 5 years | Dose escalation |
| Incidence and severity of Serious Adverse Events (SAEs) | Up to 5 years | Dose escalation |
| Incidence and severity of Adverse Events of Special Interest (AESIs) | Up to 5 years | Dose escalation |
| REGN4336 monotherapy concentrations in serum | Up to 5 years | Dose escalation |
| REGN4336 concentrations in serum in combination with REGN5678 | Up to 5 years | Dose escalation |
| Composite Response Rate (CRR) of ≥50% decline of prostate specific antigen (PSA) and/or confirmed radiographic response of complete response (CR) or partial response (PR) | Up to 5 years | Dose expansion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRR of ≥50% decline of PSA and/or confirmed radiographic response of CR or PR | Up to 5 years | Dose escalation |
| Anti-Drug Antibodies (ADA) to REGN4336 | Up to 5 years | Dose escalation |
| ADA to REGN4336 and REGN5678 | Up to 5 years | Dose escalation and dose expansion |
| Incidence and severity of TEAEs | Up to 5 years | Dose expansion |
| Incidence and severity of SAEs | Up to 5 years | Dose expansion |
| Incidence and severity of AESIs | Up to 5 years | Dose expansion |
| REGN4336 concentrations in serum in combination with REGN5678 | Up to 5 years | Dose expansion |
| Percentage of patients with ≥50% reduction in PSA confirmed by a second PSA test ≥3 weeks later | Up to 5 years | Dose escalation and dose expansion |
| Percentage of patients with ≥90% reduction in PSA confirmed by a second PSA test ≥3 weeks later | UP to 5 years | Dose escalation and dose expansion |
Countries
United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed