Clear Cell Renal Cell Carcinoma (ccRCC), Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Conditions
Brief summary
The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug\[s\]) and effectiveness (ability to treat the cancer) of REGN5678 (Nezastomig) 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
Interventions
DRUGREGN5678
Administered as per the protocol
DRUGCemiplimab
Administered as per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: mCRPC cohorts (men): 1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma. 2. 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. 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol ccRCC cohorts (men and women): 1. 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 a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC 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 described 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, as described in the protocol 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) | Through study completion, up to 5 years | Dose Escalation Phase |
| Incidence and severity of Adverse Event of Special Interests (AESIs) | Through study completion, up to 5 years | Dose Escalation Phase |
| Incidence and severity of Serious Adverse Events (SAEs) | Through study completion, up to 5 years | Dose Escalation Phase |
| Number of participants with Grade ≥3 laboratory abnormalities | Through study completion, up to 5 years | Dose Escalation Phase |
| Incidence of Dose-Limiting Toxicities (DLTs) | First dose through day 42 of last participant in each dose level | Dose Escalation Phase |
| Concentration of REGN5678 in serum over time | Through study completion, up to 5 years | Dose Escalation Phase |
| Concentration of REGN5678 in combination with cemiplimab in serum over time | Through study completion, up to 5 years | Dose Escalation Phase |
| Composite Response Rate (CRR) of 50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic response of complete (CR) or partial response (PR) | Through study completion, up to 5 years | Dose Expansion Phase - mCRPC cohort |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria | Through study completion, up to 5 years | Dose Expansion Phase - ccRCC cohort |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRR of 50% decline of PSA and/or confirmed radiographic of CR or PR | Through study completion, up to 5 years | Dose Escalation Phase - mCRPC cohort |
| ORR per RECIST 1.1 criteria | Through study completion, up to 5 years | Dose Escalation Phase - ccRCC cohort |
| Incidence and severity of TEAEs | Through study completion, up to 5 years | Dose Expansion Phase |
| Incidence and severity of AESIs | Through study completion, up to 5 years | Dose Expansion Phase |
| Incidence and severity of SAEs | Through study completion, up to 5 years | Dose Expansion Phase |
| Number of participants with grade ≥3 laboratory abnormalities | Through study completion, up to 5 years | Dose Expansion Phase |
| Concentration of REGN5678 in serum over time | Through study completion, up to 5 years | Dose Expansion Phase |
| Concentration of REGN5678 in combination with cemiplimab in serum over time | Through study completion, up to 5 years | Dose Expansion Phase |
| Percentage of participants with ≥50% decline of PSA | Through study completion, up to 5 years | Dose Escalation and Dose Expansion Phases - mCRPC cohorts |
| Percentage of participants with ≥90% decline of PSA | Through study completion, up to 5 years | Dose Escalation and Dose Expansion Phases- mCRPC cohorts |
| Presence or absence of antibodies against REGN5678 | Through study completion, up to 5 years | Dose Escalation and Dose Expansion Phases |
| Presence or absence of antibodies against cemiplimab | Through study completion, up to 5 years | Dose Escalation and Dose Expansion Phases |
Countries
United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trials Management
Regeneron Pharmaceuticals
Outcome results
None listed