A Study to Investigate the Safety and Tolerability of Oral INR731 Single Agent or in Combination With Androgen Receptor Pathway Inhibitor (ARPI) in Patients With Metastatic Prostate Cancer

Официальное название

An Open-label, Multi-center, First in Human Phase I Global Dose Escalation and Expansion Study of INR731 Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer

Обзор

The purpose of this study is to assess the safety, tolerability, pharmacokinetics/pharmacodynamics, preliminary anti-tumor activity, and recommended dose of INR731 as a single agent and in combination with standard-of-care androgen receptor pathway inhibitors (ARPIs) in adult patients with metastatic prostate cancer.

Подробное описание

This is a first-in-human, open-label, phase I, multi-center study which consists of three treatment arms: INR731 single agent (Arm A), and INR731 in combination with enzalutamide (Arm B) or abiraterone (Arm C).

The single agent arm has a dose escalation part followed by a dose expansion part. Once the single agent recommended dose(s) is determined during dose escalation, the study may proceed to dose expansion to further explore safety, tolerability and preliminary anti-tumor activity. The single agent dose expansion part will include a post-standard of care (SOC) metastatic castration resistant prostate cancer (mCRPC) group and patients with time to castration resistance (TTCR) \<12 months.

The combination arms have a dose escalation of INR731 in combination with enzalutamide or abiraterone followed by a dose expansion of INR731 in combination with enzalutamide only. The combination dose escalation will be conducted in patients with mCRPC who have progressed following standard of care (post-SOC). During combination escalation, once the safety and tolerability of INR731 with the combination agent(s) is assessed, the study may proceed to dose expansion. The combination dose expansion part will include first-line (1L) mCRPC patients with no prior treatment in the mCRPC setting.

Вмешательства

• Препарат INR731
  Oral administration
• Препарат Enzalutamide
  Oral administration
• Препарат Abiraterone
  Oral administration
• Препарат Androgen deprivation therapy (ADT)
  Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.

Первичные конечные точки

• Incidence and severity of dose-limiting toxicities (DLTs) [Срок оценки: 28 days]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to approximately 24 months]
• Frequency of dose interruptions and reductions [Срок оценки: Up to approximately 24 months]
• Dose intensity [Срок оценки: Up to approximately 24 months]

Вторичные конечные точки (10)

• Overall Response Rate (ORR) [Срок оценки: Up to approximately 24 months]
• Disease Control Rate (DCR) [Срок оценки: Up to approximately 24 months]
• Radiological Progression Free Survival (rPFS) [Срок оценки: Up to approximately 24 months]
• Prostate-Specific Antigen 50% response rate (PSA50 rate) [Срок оценки: Up to approximately 24 months]
• Area under the plasma concentration-time curve (AUC) of INR731 [Срок оценки: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.]
• Maximum plasma concentration (Cmax) of INR731 [Срок оценки: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.]
• Time to reach maximum plasma concentration (Tmax) of INR731 [Срок оценки: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.]
• Trough concentration (Ctrough) of INR731 [Срок оценки: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.]
• Plasma concentrations of study drugs [Срок оценки: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.]
• Progression Free Survival (PFS) [Срок оценки: Up to approximately 24 months]

Критерии участия

Критерии включения

• An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2.
• Participants must have histological and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are eligible as long as the non-adenocarcinoma feature is the minority component.
• At least 1 metastatic lesion (according to local radiology assessment by the investigator) present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to Cycle 1 Day 1 (C1D1).
• Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
• Ongoing androgen deprivation therapy (ADT) either via orchiectomy and/or ongoing gonadotropin-releasing hormone (GnRH) analog or inhibitor is allowed.
• Participants must be mCRPC patients who have either progressed on or are not candidates for other SOC. Prior taxane, poly(ADP) ribose polymerase (PARP) inhibitor, and lutetium Lu 177 vipivotide tetraxetan (Pluvicto) are allowed. Combination expansion patients, however, must be 1L mCRPC with no prior treatment in the mCRPC setting. Treatment within the mHSPC setting does not affect eligibility.

Критерии исключения

• Age < 18 years old.
• Histological and/or cytological confirmation of non-adenocarcinoma of the prostate.
• Patients with biochemical recurrence only or those without evidence of metastatic disease by radiographical imaging (CT/MRI or bone scan) are not eligible.
• Patients previously treated with a cereblon-based degrader.
• Patients who are HIV+ or immune compromised.
• Use of agents known to prolong QT interval unless they can be permanently discontinued for the duration of the study
• Treatment with an investigational agent within 7 days (or 5 half-lives, whichever is longer) of the anticipated Cycle 1 Day 1 (C1D1).

Other protocol-defined inclusion/exclusion criteria may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Mary Crowley Cancer Research — Dallas

Австралия · 1 центр

• Novartis Investigative Site — Melbourne

Япония · 1 центр

• Novartis Investigative Site — Hirakata

Идентификаторы

NCT: NCT07570979 · CINR731A12101 · 2025-524080-20

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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