A Study of FG-3246 in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Официальное название

A Phase 2 Dose Optimization Trial Evaluating a CD46-Targeted Antibody-Drug Conjugate (FG-3246) in Patients With Metastatic Castration-Resistant Prostate Cancer

Обзор

The purpose of this study is to evaluate the safety, efficacy, tolerability, and pharmacokinetics (PK) of FG-3246, a cluster of differentiation 46 (CD46) targeting antibody-drug conjugate (ADC), in the treatment of participants with mCRPC who have progressed following treatment with one prior second-generation androgen receptor signaling inhibitor (ARSI) in any setting and no prior taxane therapy in the mCRPC setting.

Вмешательства

• Препарат FG-3246
  FG-3246 will be administered per schedule specified in the arm description.

Первичные конечные точки

• Radiographic Progression-free Survival (rPFS) By Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria [Срок оценки: Until radiographic progression is noted (up to approximately 25 months)]
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Срок оценки: From first dose until 28 days after last dose (up to approximately 25 months)]
• Maximum Plasma Concentration (Cmax) of FG-3246, Total Anti-cluster of Differentiation 46 Antibody (CD46), and Free Monomethyl Auristatin E (MMAE) [Срок оценки: Within each 21 day treatment cycle from Cycle 1 through 28 days post last dose (up to approximately 25 months)]

Вторичные конечные точки (12)

• rPFS Rate at 6 Months (rPFS6) Per RECIST v1.1 and PCWG3 Criteria [Срок оценки: Month 6]
• rPFS Rate at 12 Months (rPFS12) Per RECIST v1.1 and PCWG3 Criteria [Срок оценки: Month 12]
• Confirmed Objective Response Rate (ORR) Per RECIST v1.1 and PCWG3 Criteria [Срок оценки: From first dose up to approximately 25 months]
• Duration of Response (DoR) Per RECIST v1.1 and PCWG3 Criteria [Срок оценки: From first dose up to approximately 25 months]
• Confirmed PSA50 Response Rate: Percentage of Participants Achieving a Decline in Prostate-specific Antigen (PSA) ≥50% From Baseline [Срок оценки: Up to approximately 25 months]
• Confirmed PSA90 Response Rate: Percentage of Participants Achieving a Decline in PSA ≥90% From Baseline [Срок оценки: Up to approximately 25 months]
• Composite Response Rate (CRR) Per RECIST 1.1 and PCWG3 Criteria [Срок оценки: Up to approximately 25 months]
• PSA Progression-free Survival (PFS) [Срок оценки: Up to approximately 25 months]
• Disease Control Rate (DCR) per RECIST 1.1 and PCWG3 Criteria [Срок оценки: Up to approximately 25 months]
• Clinical Benefit Rate (CBR) per RECIST 1.1 and PCWG3 Criteria [Срок оценки: Up to approximately 25 months]
• Time to First Symptomatic Skeletal-related Event (SSRE) [Срок оценки: Up to approximately 25 months]
• Overall Survival (OS) [Срок оценки: Until death or up to approximately 25 months]

Критерии участия

Критерии включения

• Participant must have histological, and/or cytological confirmation of prostate adenocarcinoma on all prior tumor biopsies.
• Participant with soft tissue disease and a safely accessible soft tissue tumor lesion(s) must agree to biopsy of a primary or metastatic lesion during screening. Alternatively, participant may provide a suitable archival biopsy of a primary or metastatic lesion.
• Participant must have serum testosterone levels <50 nanograms (ng)/deciliter (dL) during screening.
• Participant is required to have progressed on no more than one prior treatment with a second generation ARSI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) initiated in either the castration-sensitive or castration-resistant setting.
• Participant must have progressive mCRPC following last treatment at screening.
• Participant must have ≥1 metastatic lesion that is present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or bone scan obtained ≤28 days prior to randomization.
• Participant must have adequate organ function during screening.

Критерии исключения

• Participant has received previous treatment with a therapeutic targeting CD46.
• Participant has small cell neuroendocrine carcinoma (pure or mixed) on any prior histologic evaluation of primary or metastatic lesion.
• Participant has progressed on more than one prior second-generation ARSI in any setting or has received more than two prior second-generation ARSIs in any setting.
• Participants must not have received recent anticancer treatments before enrollment. Ongoing supportive or hormonal therapies are allowed if they were started well before randomization and are continued without change.
• Participant has received any prior radiation therapy within 14 days prior to randomization.
• Participant has a known actionable mutation or gene alteration, for example, BRCA1 mutation, for which approved therapies are available, for example, PARP inhibitors, unless these therapies are not appropriate for the participant as determined by the investigator or the participant refuses such therapy.
• Participant has National Cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 2 peripheral neuropathy at the time of screening from any etiology.
• Participant has received any prior chemotherapy; however, one prior taxane-based chemotherapy in the castration-sensitive setting is allowed if completed >12 months before randomization.
• Participant has known hypersensitivity to the components of FG-3246 or its analogs or a history of allergic or anaphylactic reaction to human, humanized, or chimeric monoclonal antibodies.
• Participant has diagnosis with any other malignancy in the past 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin.
• Participant requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer drug that cannot be safely discontinued.

NOTE: Other protocol-defined inclusion/exclusion may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 20 центров

• Western Regional Medical Center - City of Hope Phoenix Goodyear — Goodyear
• HonorHealth Research Institute — Scottsdale
• The University of Arizona Cancer Center - North Campus — Tucson
• VA Greater Los Angeles Healthcare System — Los Angeles
• UCLA Clark Urology Center — Los Angeles
• University of California San Francisco — San Francisco
• New Haven Hospital - Yale Cancer Center — New Haven
• Bioresearch Partner - Aventura — Aventura
• … и ещё 12 центров

Идентификаторы

NCT: NCT06842498 · FGCL-3246-112

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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