A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)

Официальное название

A Phase 2 Open-Label, Multi-Center Study of BMS-986504 as Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion

Обзор

This is an open-label, multicenter Phase 2 study evaluating BMS-986504 in participants with advanced and/or metastatic solid tumors that have MTAP deletion. The study includes a monotherapy component and a combination component in which BMS-986504 is given with other anti-cancer agents. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of BMS-986504 alone and in combination regimens.

Подробное описание

Part 1 will include parallel enrolment of tumor-specific dose-expansion cohorts evaluating BMS-986504 as monotherapy. Part 2 will include dose-escalation cohorts in which BMS-986504 is given in combination with other anticancer agents. Additional cohorts may be added based on emerging data.

Вмешательства

• Препарат BMS-986504
  Specified dose on specified days
• Препарат Daraxonrasib
  Specified dose on specified days
• Препарат Nivolumab + Relatlimab FDC
  Specified dose on specified days
• Препарат Temozolomide
  Specified dose on specified days
• Препарат Pumitamig
  Specified dose on specified days
• Препарат Pemetrexed
  Specified dose on specified days
• Препарат Carboplatin
  Specified dose on specified days
• Препарат Nab-paclitaxel
  Specified dose on specified days
• Препарат Gemcitabine
  Specified dose on specified days
• Препарат Paclitaxel
  Specified dose on specified days

Первичные конечные точки

• Part 1: Number of participants who achieve Objective Response (OR) [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with adverse events meeting protocol defined dose limiting toxicities (DLTs) criteria [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with adverse events (AE) [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with Serious AEs (SAEs) [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with treatment related AEs [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with treatment related SAEs [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with AEs leading to study treatment discontinuation [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with AEs leading to death [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants with laboratory abnormalities [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (12)

• Part 1 and 2: Time to objective response (TTOR) [Срок оценки: Up to approximately 2 years]
• Part 1 and 2: Duration of response (DOR) [Срок оценки: Up to approximately 2 years]
• Part 1 and 2: Number of participants who achieve disease control (DC) [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with adverse events (AE) [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with Serious AEs (SAEs) [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with treatment related AEs [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with treatment related SAEs [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with AEs leading to study treatment discontinuation [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with AEs leading to death [Срок оценки: Up to approximately 2 years]
• Part 1: Number of participants with laboratory abnormalities [Срок оценки: Up to approximately 2 years]
• Part 2: Number of participants who achieve Objective Response (OR) [Срок оценки: Up to approximately 2 years]
• Part 1 and 2: Number of participants who achieved clinical benefit (CB) [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
• Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease.
• Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer must be ≤ 2 × ULN.
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Критерии исключения

• Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor.
• Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Participants must not have history of gastrointestinal disease or other gastrointestinal conditions within 6 months prior to enrollment (including uncontrolled nausea, vomiting, malabsorption syndrome or non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess) likely to alter absorption of study treatment or result in inability to swallow oral medications.
• Participants must not have inadequate organ function, as determined by laboratory testing within the screening period.
• Participants must not have active viral HBV or HCV hepatitis.
• Other protocol defined inclusion/exclusion criteria applies.

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 · 16 центров

• Local Institution - 0096 — San Francisco
• Local Institution - 0182 — Aurora
• Local Institution - 0178 — Atlanta
• Johns Hopkins Hospital — Baltimore
• Local Institution - 0124 — Boston
• Local Institution - 0119 — Ann Arbor
• Local Institution - 0129 — Rochester
• Local Institution - 0174 — Rochester
• … и ещё 8 центров

Китай · 6 центров

• Local Institution - 0155 — Пекин
• Local Institution - 0185 — Чунцин
• Local Institution - 0184 — Гуанчжоу
• Local Institution - 0152 — Xinxiang
• Shanghai GoBroad Cancer Hospital China Pharmaceutical University — Шанхай
• Fudan University Shanghai Cancer Center — Шанхай

Германия · 6 центров

• Local Institution - 0081 — Mainz
• Local Institution - 0040 — Hamburg
• Local Institution - 0039 — Heidelberg
• Local Institution - 0061 — Leipzig
• Local Institution - 0049 — München
• Local Institution - 0047 — Würzburg

Италия · 5 центров

• Local Institution - 0073 — Siena
• Local Institution - 0123 — Bergamo
• Local Institution - 0034 — Milan
• Local Institution - 0050 — Naples
• Local Institution - 0082 — Perugia

Франция · 4 центра

• Local Institution - 0078 — Dijon
• Local Institution - 0075 — Pierre-Bénite
• Local Institution - 0116 — Villejuif
• Local Institution - 0074 — Paris

Испания · 4 центра

• Local Institution - 0068 — Barcelona
• Local Institution - 0071 — Hospitalet
• Local Institution - 0033 — Madrid
• Local Institution - 0069 — Seville

Канада · 3 центра

• Local Institution - 0051 — Vancouver
• Local Institution - 0021 — Toronto
• Local Institution - 0007 — Toronto

Ирландия · 3 центра

• Local Institution - 0080 — Cork
• Local Institution - 0023 — Dublin
• Local Institution - 0146 — Dublin

South Korea · 3 центра

• Local Institution - 0004 — Seoul
• Local Institution - 0058 — Seoul
• Local Institution - 0052 — Seoul

Бельгия · 2 центра

• Local Institution - 0148 — Brussels
• Local Institution - 0114 — Ghent

Гонконг · 2 центра

• Local Institution - 0150 — Hksar
• Local Institution - 0063 — Shatin

Норвегия · 2 центра

• Local Institution - 0171 — Bergen
• Local Institution - 0022 — Oslo

Япония · 1 центр

• National Cancer Center Hospital — Chuo-ku

Идентификаторы

NCT: NCT07492680 · CA240-0005 · 2025-524285-18 · U1111-1330-1428

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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