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.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 21
- 主要终点
- Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
研究概览
简要总结
"Part 1: Determine the safety and tolerability, and the recommended dose for expansion (RDE) and/or maximum tolerated dose (MTD) for GSK5460025 as monotherapy Part 2: Evaluate the preliminary anti-tumor activity of GSK5460025 as monotherapy in Colorectal cancer (CRC) and, separately, Endometrial cancer (EC) "
研究设计
- 分配方式
- Non Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Participant is at least 18 years of age.
- •Part 2: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) Colorectal cancer (CRC) or Endometrial cancer (EC).
- •Part 2: Participant 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.
- •Part 2: Participant has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator.
- •Participant has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor.
- •Participant 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.
- •Participant provides an archival or fresh (preferred) formalin fixed, paraffin embedded (FFPE) sample.
- •Participant intends to receive GSK5460025 (as described in the protocol) as next treatment.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Participant is expected to have a minimum of 3 months life expectancy.
- •Participant has adequate organ function, as defined in the protocol.
- •Part 1: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options.
排除标准
- •Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced Adverse Events (AEs).
- •Participant has received prior treatment with a Werner (WRN) inhibitor or Nucleotide Excision Repair Targeting (NERT) agent.
- •Participant is unable to swallow and retain orally administered study treatment.
- •Participant has untreated or progressed metastases in brain or CNS.
- •Participant 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.
- •Participant has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs.
- •Participant has cirrhosis or current unstable liver or biliary disease.
- •Participant has known hypersensitivity to any of the study interventions or any of their excipients.
研究组 & 干预措施
null, null, null
干预措施: null, null, null (Drug)
结局指标
主要结局
Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
Part 1: Number of participants with dose limiting toxicities (DLTs) per dose level
Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level
Part 1: Number of participants with treatment emergent serious adverse events (TESAEs) and treatment emergent adverse events (TEAEs) by severity per dose level
Part 1: Duration of TESAEs and TEAEs per dose level
Part 1: Duration of TESAEs and TEAEs per dose level
Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period
Part 1: Number of participants with TESAEs and TEAEs by severity per dose level during DLT observation period
Part 1: Number of participants with dosage modifications due to TEAEs per dose level
Part 1: Number of participants with dosage modifications due to TEAEs per dose level
"Part 2: Objective Response Rate (ORR) ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator assessment."
"Part 2: Objective Response Rate (ORR) ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator assessment."
次要结局
- Part 2: Plasma concentration of GSK5460025
- Part 1: Plasma concentrations for GSK5460025
- Part 1: Area under the concentration-time curve (AUC) for GSK5460025
- Part 1: Time to maximum concentration (Tmax) for GSK5460025
- Part 1: Number of participants with clinically important changes in laboratory parameters, Electrocardiogram (ECGs), and vital signs per dose level
- Part 2: Number of participants with TESAEs and TEAEs by severity
- Part 2: Number of participants with TEAEs leading to dosage modifications
- Part 2: Number of participants with clinically important changes in laboratory parameters, ECGs, and vital signs
- PFS is defined as time from first dose to progressive disease (as assessed per RECIST 1.1 by Investigator assessment) or death from any cause, whichever is earlier
- DoR is defined as time from first documented PR or CR to progressive disease (as assessed per RECIST 1.1 by investigator assessment) or death from any cause, whichever is earlier for participants who have achieved a confirmed CR or PR.
研究者
EU GSK Clinical Trials Call Center
Scientific
Glaxosmithkline Research & Development Limited