AMG 436 as Monotherapy and Combination Therapy in Participants With MSI-H/dMMR Solid Tumors

Официальное название

A Phase 1/1b Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AMG 436 as Monotherapy and in Combination With Other Therapies in Participants With Microsatellite Instability-high (MSI-H)/Mismatch Repair Deficient (dMMR) Solid Tumors

Обзор

The primary objectives of this trial are to evaluate the safety profile of AMG 436 and to determine the maximum tolerated dose (MTD) and/or the recommended dose for AMG 436 as monotherapy and in combination with other anti-cancer therapies in participants with MSI-H/dMMR solid tumors.

Вмешательства

• Препарат AMG 436
  AMG 436 will be administered.

Первичные конечные точки

• Number of Participants with a Dose Limiting Toxicity (DLT) [Срок оценки: Up to 21 days]
• Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to 5 years]

Вторичные конечные точки (12)

• Maximum Serum Concentration (Cmax) of AMG 436 [Срок оценки: Up to 57 days]
• Minimum Serum Concentration (Cmin) of AMG 436 [Срок оценки: Up to 57 days]
• Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436 [Срок оценки: Up to 57 days]
• Time to Achieve Cmax (Tmax) of AMG 436 [Срок оценки: Up to 57 days]
• Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State [Срок оценки: Up to 24 days]
• Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State [Срок оценки: Up to 24 days]
• Part 1B: AUC Over the Dosing Interval of AMG 436 in the Fed and/or Fasted State [Срок оценки: Up to 24 days]
• Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Срок оценки: Up to 5 years]
• Duration of Response (DOR) per RECIST v1.1 [Срок оценки: Up to 5 years]
• Time to Response (TTR) per RECIST v1.1 [Срок оценки: Up to 5 years]
• Disease Control Rate (DCR) per RECIST v1.1 [Срок оценки: Up to 5 years]
• Progression-free Survival (PFS) per RECIST v1.1 [Срок оценки: Up to 5 years]

Критерии участия

Критерии включения

• Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
• Histologically confirmed MSI-H or dMMR metastatic or locally advanced solid tumor by local testing or central testing.
• Tumor tissue (formalin-fixed, paraffin-embedded sample) archival block must be available. Participants without archived tumor tissue may enroll by undergoing tumor biopsy before dosing.
• Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
• Eastern Cooperative Oncology Group performance (ECOG) 0-1.
• Adequate organ function as defined in the protocol.

Критерии исключения

• Participants with primary central nervous system (CNS) tumors.
• Impaired cardiac function or clinically significant cardiac disease.
• Major surgery within 28 days of trial day 1.
• Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 21 days of first dose of trial treatment, unless anti-tumor therapy is a therapy with 5 times the half-life being shorter than 21 days (in this case, enrollment may be allowed with washout from prior therapy of < 21 days.
• Radiation therapy within 28 days of the first dose of trial treatment (or local or focal radiotherapy with palliative intent within 14 days of the first dose).
• Gastrointestinal tract disease causing the inability to take per os (PO) medication, malabsorption syndrome, requirement for intravenous (IV) alimentation, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).

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 · 6 центров

• City of Hope Orange County Lennar Foundation Cancer Center — Irvine
• Midwestern Regional Medical Center dba City of Hope Chicago — Zion
• Community Health Network MD Anderson Cancer Center - North — Indianapolis
• New England Cancer Specialists — Westbrook
• Tennessee Oncology PLLC — Nashville
• Next Oncology - Dallas — Irving

Япония · 4 центра

• Aichi Cancer Center — Nagoya
• National Cancer Center Hospital East — Kashiwa-shi
• National Cancer Center Hospital — Chuo-ku
• The Cancer Institute Hospital of Japanese Foundation for Cancer Research — Koto-ku

Испания · 3 центра

• Hospital Universitari Vall d Hebron — Barcelona
• Hospital Clinic i Provincial de Barcelona — Barcelona
• Clinica Universidad de Navarra — Madrid

Австралия · 2 центра

• Calvary Mater Newcastle Hospital — Waratah
• Peter MacCallum Cancer Centre — Melbourne

Бельгия · 2 центра

• Universite Catholique de Louvain Cliniques Universitaires Saint Luc — Brussels
• Universitair Ziekenhuis Gent — Ghent

Китай · 2 центра

• Sun Yat-Sen University Cancer Center — Гуанчжоу
• Zhongshan Hospital Fudan University — Шанхай

Франция · 2 центра

• Hopital Saint Antoine — Paris
• Gustave Roussy — Villejuif

Канада · 1 центр

• Princess Margaret Cancer Centre — Toronto

South Korea · 1 центр

• Asan Medical Center — Seoul

Тайвань · 1 центр

• Taipei Veterans General Hospital — Taipei

Идентификаторы

NCT: NCT07403721 · 20250004 · 2025-524056-63-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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