A Trial to Find Out if REGN4336 is Safe and How Well it Works Alone and in Combination With REGN5678 for Adult Participants With Advanced Prostate Cancer

Официальное название

Phase 1/2 Study of REGN4336 (a PSMAxCD3 Bispecific Antibody) Administered Alone or in Combination With REGN5678 (a PSMAxCD28 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer

Обзор

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)

Вмешательства

• Препарат REGN4336
  Administered per the protocol
• Препарат REGN5678
  Administered per the protocol

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: up to 21 days]
• Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Up to 5 years]
• Incidence and severity of Serious Adverse Events (SAEs) [Срок оценки: Up to 5 years]
• Incidence and severity of Adverse Events of Special Interest (AESIs) [Срок оценки: Up to 5 years]
• REGN4336 monotherapy concentrations in serum [Срок оценки: Up to 5 years]
• REGN4336 concentrations in serum in combination with REGN5678 [Срок оценки: Up to 5 years]
• 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) [Срок оценки: Up to 5 years]

Вторичные конечные точки (9)

• CRR of ≥50% decline of PSA and/or confirmed radiographic response of CR or PR [Срок оценки: Up to 5 years]
• Anti-Drug Antibodies (ADA) to REGN4336 [Срок оценки: Up to 5 years]
• ADA to REGN4336 and REGN5678 [Срок оценки: Up to 5 years]
• Incidence and severity of TEAEs [Срок оценки: Up to 5 years]
• Incidence and severity of SAEs [Срок оценки: Up to 5 years]
• Incidence and severity of AESIs [Срок оценки: Up to 5 years]
• REGN4336 concentrations in serum in combination with REGN5678 [Срок оценки: Up to 5 years]
• Percentage of patients with ≥50% reduction in PSA confirmed by a second PSA test ≥3 weeks later [Срок оценки: Up to 5 years]
• Percentage of patients with ≥90% reduction in PSA confirmed by a second PSA test ≥3 weeks later [Срок оценки: UP to 5 years]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
• 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:

• PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment
• Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression
• 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
• 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)

Критерии исключения

• 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
• 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
• 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
• 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
• 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 Virus (HBV), or Hepatitis C Virus (HCV) infection; or diagnosis of immunodeficiency, as described in the protocol.

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 · 14 центров

• Stanford University Medical Center - Blake Wilbur Drive — Palo Alto
• Yale University Hospital — New Haven
• Norton Cancer Institute — Louisville
• University of Maryland Greenebaum Cancer Center — Baltimore
• Rutgers Cancer Institute of New Jersey — New Brunswick
• Roswell Park Cancer Institute — Buffalo
• Atrium Health Levine Cancer Institute — Charlotte
• The Ohio State University James Cancer Hospital — Columbus
• … и ещё 6 центров

Идентификаторы

NCT: NCT05125016 · R4336-ONC-20104 · 2022-502130-17-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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