A Study of DS9051b in Participants With Advanced or Metastatic Adrenocortical Carcinoma and Metastatic Castration-resistant Prostate Cancer

Официальное название

A Phase 1, First-in-human (FIH), Multicenter, Open-label Trial of DS9051b in Participants With Advanced or Metastatic Adrenocortical Carcinoma (ACC) and Metastatic Castration-resistant Prostate Cancer (mCRPC)

Обзор

This FIH study is designed to assess the safety, tolerability, and preliminary efficacy signals of DS9051b in participants with ACC and mCRPC.

Подробное описание

The purpose of the dose escalation part is to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE), as well as to establish the safety profile of DS9051b in participants with advanced or metastatic ACC and mCRPC.

Вмешательства

• Препарат DS9051b
  Administered orally

Первичные конечные точки

• Number of Participants Reporting Dose-limiting Toxicities (DLTs), Treatment-emergent Adverse Events (TEAEs), TEAEs Associated With Treatment Discontinuation, Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) - All Patients [Срок оценки: Baseline up to 50 months]

Вторичные конечные точки (5)

• Objective Response by Investigator Assessment in Participants With Advanced or Metastatic Adrenocortical Carcinoma and Metastatic Castration-resistant Prostate Cancer [Срок оценки: Baseline up to 50 months]
• Disease Control by Investigator Assessment in Participants With Advanced or Metastatic Adrenocortical Carcinoma and Metastatic Castration-resistant Prostate Cancer [Срок оценки: Baseline up to 50 months]
• Clinical Benefit by Investigator Assessment in Participants With Advanced or Metastatic Adrenocortical Carcinoma and Metastatic Castration-resistant Prostate Cancer [Срок оценки: Baseline up to 50 months]
• Duration of Response by Investigator Assessment in Participants With Advanced or Metastatic Adrenocortical Carcinoma and Metastatic Castration-resistant Prostate Cancer [Срок оценки: From date of initial response (CR or PR) to the earlier date of the first objective documentation of radiographic disease progression (based on investigator assessment per RECIST v1.1) or death due to any cause, up to 50 months]
• Progression-free Survival by Investigator Assessment in Participants With Advanced or Metastatic Adrenocortical Carcinoma [Срок оценки: From the date of the first administration of trial intervention to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to 50 months]

Критерии участия

General Inclusion Criteria for All Participants

• Sign and date the main ICF, prior to the start of any trial-specific procedures.
• Adults ≥18 years of age at the time the ICF is signed (Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old)
• Histologically confirmed diagnosis of ACC or adenocarcinoma of the prostate
• ECOG PS of 0 or 1 assessed no more than 14 days prior to C1D1. (ECOG PS of 2 due to cancer pain is acceptable)
• Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to C1D1 as defined below. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days of initiation of trial intervention as appropriate.

Additional Inclusion Criteria for Participants with mCRPC

• Treatment with at least 1 line (or more) of ARPI therapy for CSPC or in CRPC for a minimum of 12 weeks (eg, abiraterone, enzalutamide, darolutamide, apalutamide).
• Treatment with at least 1 line (or more) of chemotherapy, having ineligibility for chemotherapy or refusal of chemotherapy.
• Documented disease progression by one or more of the following criteria:

• PSA progression as defined by PCWG3 criteria.
• Soft tissue disease progression as defined by RECIST 1.1 criteria.
• Bone disease progression as defined by Prostate Cancer Working Group 3 criteria.

An individual who meets any of the following criteria will be excluded from participation in this trial:

• History of pituitary gland dysfunction.
• Active or uncontrolled autoimmune disease requiring systemic treatment.
• Any medical condition (other than the cancer disease) requiring a dose of concurrent systemic corticosteroid treatment greater than 5 mg of prednisone and/or 100 μg of fludrocortisone per day (or equivalent).
• Active infection or other medical conditions that would make corticosteroids contraindicated.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated, clinically progressive, symptomatic, or requiring systemic therapy with corticosteroids or anticonvulsants or local therapy (ie, radiotherapy) to control associated symptoms.
• Uncontrolled or significant cardiovascular disease.
• History of another primary malignancy (beyond the indication\[s\] under study) except for:

• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of trial intervention and of low potential risk for recurrence.
• Non-melanoma skin cancer, lentigo maligna, or lentigo maligna melanoma treated with curative intent and without evidence of disease.
• Carcinoma in situ treated with curative intent and without evidence of disease.
• Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who, in the opinion of the investigator, are not deemed to require active intervention.
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, Grade ≤1 or baseline.
• Participants who cannot swallow whole DS9051b tablets and/or follow DS9051b administration schedule at protocol-defined frequency due to some reasons (eg, dysphagia etc).
• Known gastrointestinal disease or gastrointestinal procedure that may interfere with absorption of trial intervention including proton pump inhibitors and antacids.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Florida Cancer Specialists — Sarasota
• Columbia University — New York
• Brown University — Providence

Франция · 2 центра

• Oncopole Claudius Regaud — Toulouse
• Centre Oscar Lambret — Villejuif

Великобритания · 1 центр

• Royal Marsden — London

Идентификаторы

NCT: NCT07189403 · DS9051-079 · 2025-521886-28-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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