A Trial to Find Out if REGN5678 (Nezastomig) 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

Официальное название

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

Обзор

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

Вмешательства

• Препарат REGN5678
  Administered as per the protocol
• Препарат Cemiplimab
  Administered as per the protocol

Первичные конечные точки

• Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Through study completion, up to 5 years]
• Incidence and severity of Adverse Event of Special Interests (AESIs) [Срок оценки: Through study completion, up to 5 years]
• Incidence and severity of Serious Adverse Events (SAEs) [Срок оценки: Through study completion, up to 5 years]
• Number of participants with Grade ≥3 laboratory abnormalities [Срок оценки: Through study completion, up to 5 years]
• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: First dose through day 42 of last participant in each dose level]
• Concentration of REGN5678 in serum over time [Срок оценки: Through study completion, up to 5 years]
• Concentration of REGN5678 in combination with cemiplimab in serum over time [Срок оценки: Through study completion, up to 5 years]
• Composite Response Rate (CRR) of 50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic response of complete (CR) or partial response (PR) [Срок оценки: Through study completion, up to 5 years]
• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [Срок оценки: Through study completion, up to 5 years]

Вторичные конечные точки (12)

• CRR of 50% decline of PSA and/or confirmed radiographic of CR or PR [Срок оценки: Through study completion, up to 5 years]
• ORR per RECIST 1.1 criteria [Срок оценки: Through study completion, up to 5 years]
• Incidence and severity of TEAEs [Срок оценки: Through study completion, up to 5 years]
• Incidence and severity of AESIs [Срок оценки: Through study completion, up to 5 years]
• Incidence and severity of SAEs [Срок оценки: Through study completion, up to 5 years]
• Number of participants with grade ≥3 laboratory abnormalities [Срок оценки: Through study completion, up to 5 years]
• Concentration of REGN5678 in serum over time [Срок оценки: Through study completion, up to 5 years]
• Concentration of REGN5678 in combination with cemiplimab in serum over time [Срок оценки: Through study completion, up to 5 years]
• Percentage of participants with ≥50% decline of PSA [Срок оценки: Through study completion, up to 5 years]
• Percentage of participants with ≥90% decline of PSA [Срок оценки: Through study completion, up to 5 years]
• Presence or absence of antibodies against REGN5678 [Срок оценки: Through study completion, up to 5 years]
• Presence or absence of antibodies against cemiplimab [Срок оценки: Through study completion, up to 5 years]

Критерии участия

Критерии включения

mCRPC cohorts (men):

• Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
• PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.
• 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:

• one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
• 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol

ccRCC cohorts (men and women):

• Histologically or cytologically confirmed RCC with a clear-cell component.
• Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
• 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

Критерии исключения

• 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
• Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
• Has received prior PSMA-targeting therapy with the exception of a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC
• Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
• Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as described in the protocol
• 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
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, as described in the protocol
• 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
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 24 центра

• Banner MD Anderson Cancer Center — Gilbert
• Mayo Clinic — Phoenix
• University of Arizona — Tucson
• John Wayne Cancer Institute (JWCI) — Santa Monica
• Sarah Cannon Research Institute (SCRI) — Denver
• Yale University Hospital — New Haven
• Mayo Clinic Jacksonville — Jacksonville
• Moffitt Cancer Center - McKinley Drive — Tampa
• … и ещё 16 центров

Идентификаторы

NCT: NCT03972657 · R5678-ONC-1879

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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