A Study to Investigate the Safety and Preliminary Efficacy of GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Participants With Solid Tumors

Официальное название

A Phase 1/2 Open-label, Multicenter Study of Oral GSK5460025 Alone or in Combination With Other Anti-cancer Agents in Adult Participants With Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) Solid Tumors

Обзор

Solid tumours are abnormal lumps of tissue that can occur in different parts of the body. The tumours involved in this study have specific genetic characteristics that can make them more aggressive and challenging to treat. The study will test whether GSK5460025 alone or in combination (potential combinations may be included in future amendments to the protocol) with other anti-cancer agents can decrease tumor size, is safe, well-tolerated, and how the drug is processed in the body over time.

Вмешательства

• Препарат GSK5460025
  GSK5460025 will be administered

Первичные конечные точки

• Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level [Срок оценки: Up to 28 days]
• Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level [Срок оценки: Up to approximately 33 months]
• Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period [Срок оценки: Up to 28 days]
• Part 1: Number of participants with dosage modifications due to TEAEs per dose level [Срок оценки: Up to approximately 33 months]
• Part 2: Objective Response Rate (ORR) [Срок оценки: Up to approximately 33 months]

Вторичные конечные точки (11)

• Part 1: Plasma concentrations for GSK5460025 [Срок оценки: Up to approximately 36 months]
• Part 1: Area under the concentration-time curve (AUC) for GSK5460025 [Срок оценки: Up to approximately 36 months]
• Part 1: Maximum concentration (Cmax) for GSK5460025 [Срок оценки: Up to approximately 36 months]
• Part 1: Time to maximum concentration (Tmax) for GSK5460025 [Срок оценки: Up to approximately 36 months]
• Part 1: Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level [Срок оценки: Up to approximately 36 months]
• Part 2: Number of participants with TESAEs and TEAEs by severity [Срок оценки: Up to approximately 36 months]
• Part 2: Number of participants with TEAEs leading to dosage modifications [Срок оценки: Up to approximately 36 months]
• Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs [Срок оценки: Up to approximately 36 months]
• Part 2: Progression-free Survival (PFS) [Срок оценки: Up to approximately 36 months]
• Part 2: Duration of Response (DoR) [Срок оценки: Up to approximately 36 months]
• Part 2: Plasma concentration of GSK5460025 [Срок оценки: Up to approximately 36 months]

Критерии участия

Критерии включения

• Has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor
• Has a known dMMR/MSI-H status as determined by a certified local laboratory at the time of Pre-screening or has an unknown Mismatch repair (MMR)/ Microsatellite Instability (MSI) status at the time of Pre-screening and MMR/MSI status will be determined by central reference laboratory
• Provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample
• Intends to receive GSK5460025 as next treatment
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Is expected to have a minimum of 3 months life expectancy
• Has adequate organ function, as defined in the protocol

Part 1 inclusion criteria:

• Has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options

Part 2 inclusion criteria:

• Has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC)
• Has received at least 1 but no more than 3 lines of systemic anticancer therapy for their advanced (unresectable, metastatic or recurrent) disease including at least one line of Immune checkpoint inhibitors (ICI) therapy
• Has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator

Критерии исключения

• Has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs)
• Has received prior treatment with a Werner (WRN) inhibitor or Nucleotide Excision Repair Targeting (NERT) agent.
• Is unable to swallow and retain orally administered study treatment
• Has untreated or progressed metastases in brain or CNS
• Has a known additional malignancy that progressed or required active treatment within the last 2 years because reoccurrence of another malignancy would confound interpretation by RECIST 1.1 criteria. Exceptions include basal or squamous cell carcinomas of the skin or in situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of metastatic disease.
• Has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs
• Has cirrhosis or current unstable liver or biliary disease
• Has known hypersensitivity to any of the study interventions or any of their excipients

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

Испания · 5 центров

• GSK Investigational Site — Barcelona
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid

США · 4 центра

• GSK Investigational Site — Aurora
• GSK Investigational Site — Detroit
• GSK Investigational Site — Canton
• GSK Investigational Site — Nashville

Япония · 4 центра

• GSK Investigational Site — Chiba
• GSK Investigational Site — Osaka
• GSK Investigational Site — Tokyo
• GSK Investigational Site — Tokyo

Канада · 3 центра

• GSK Investigational Site — Hamilton
• GSK Investigational Site — Toronto
• GSK Investigational Site — Montreal

Швеция · 3 центра

• GSK Investigational Site — Lund
• GSK Investigational Site — Stockholm
• GSK Investigational Site — Uppsala

Нидерланды · 2 центра

• GSK Investigational Site — Amsterdam
• GSK Investigational Site — Utrecht

Дания · 1 центр

• GSK Investigational Site — Copenhagen

Идентификаторы

NCT: NCT07213609 · 224035 · 2025-522318-21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗