A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Clinical Activity of RO7673396 in Participants With Advanced Solid Tumors Harboring Rat Sarcoma Viral Oncogene Homolog (RAS) Mutation(s)

Официальное название

A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Clinical Activity of RO7673396 as a Single Agent and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors Harboring RAS Mutation(s)

Обзор

This study aims to evaluate the safety and tolerability of RO7673396 in participants with advanced solid tumors harboring RAS mutation(s). This study consists of two stages: Stage 1 (Dose Escalation) and Stage 2 (Dose Expansion). Stage 1 will define the recommended dose(s) for expansion (RDEs) of RO7673396. Stage 2 will evaluate preliminary anti-tumor activity of the RDE(s) defined in Stage 1 and of other doses of interest for future development in selected solid tumor indications.

Вмешательства

• Препарат RO7673396
  RO7673396 will be administered as per the schedule specified in the protocol.

Первичные конечные точки

• Stage I: Number of Participants With Adverse Events (AEs) [Срок оценки: Up to approximately 40 months]
• Stage I: Number of Participants With Dose-limiting Toxicities (DLTs) [Срок оценки: Up to Day 21]
• Stage II: Objective Response Rate (ORR) as Assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) [Срок оценки: Up to approximately 40 months]

Вторичные конечные точки (4)

• Plasma Concentrations of RO7673396 and its Metabolite(s) [Срок оценки: Up to approximately 49 months]
• Stage I: ORR as Assessed by the Investigator per RECIST V1.1 [Срок оценки: Up to approximately 49 months]
• Stage I and II: Duration of Response (DOR) as Assessed by the Investigator per RECIST V1.1 [Срок оценки: Up to approximately 49 months]
• Stage I and II: Progression-free Survival (PFS) as Assessed by the Investigator per RECIST V1.1 [Срок оценки: Up to approximately 49 months]

Критерии участия

Критерии включения

• Histologically documented, locally advanced, recurrent, or metastatic incurable solid tumors
• Participants with measurable disease according to RECIST v1.1 assessed by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy ≥12 weeks
• Adequate hematologic and end-organ function
• Confirmed presence of the RAS mutation(s)

Критерии исключения

• Current participant or enrollment in another interventional clinical trial
• Known hypersensitivity or medical contraindication to any component of RO7673396 formulation
• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study treatment absorption
• Known and untreated, or active central nervous system (CNS) metastases
• Participants with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal (GI) surgery including gastric resection, a history of inflammatory bowel disease (IBD)
• Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 4 weeks or five half-lives prior to initiation of study treatment
• Participants who are on acid-reducing agents and unable to safely discontinue them as required in the study
• Major surgical procedure within 28 days prior to initiation of study treatment, or incomplete recovery from surgery that would interfere with the determination of safety or efficacy of study treatment, or anticipation of need for a major surgical procedure during the study
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Known clinically significant liver disease

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 Comprehensive Cancer Center — Duarte
• University of Colorado - Anschutz Medical Campus - PPDS — Aurora
• Smilow Cancer Hospital at Yale New Haven — New Haven
• Florida Cancer Specialists - Sarasota (North Catttlemen Rd) — Sarasota
• MD Anderson Cancer Center — Houston
• South Texas Accelerated Research Therapeutics (START) — San Antonio

Китай · 4 центра

• Sun Yat-Sen University Cancer Center - Huangpu Campus — Гуанчжоу
• Sun Yat-Sen University Cancer Center;Department of Thoracic Surgery — Гуанчжоу
• Fudan University Shanghai Cancer Center — Шанхай
• Hubei Cancer Hospital — Ухань

Австралия · 2 центра

• St Vincent's Hospital Sydney — Darlinghurst
• Peter MacCallum Cancer Center — Parkville

Новая Зеландия · 2 центра

• New Zealand Clinical Research - Auckland — Auckland
• New Zealand Clinical Research - Christchurch — Christchurch

Тайвань · 2 центра

• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei

Канада · 1 центр

• Princess Margaret Hospital — Toronto

Дания · 1 центр

• Rigshospitalet — København Ø

Гонконг · 1 центр

• Prince of Wales Hospital — Гонконг

Сингапур · 1 центр

• National Cancer Centre - 30 Hospital Blvd — Singapore

Испания · 1 центр

• Clinica Universidad de Navarra — Pamplona

Идентификаторы

NCT: NCT06884618 · YO45758 · 2024-519622-20-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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