A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-133214 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)

Vividion Therapeutics, Inc.48 个研究点分布在 9 个国家目标入组 295 人2024年1月25日

适应症Advanced Solid Tumors

干预措施VVD-133214 Pembrolizumab

概览

阶段: 1 期
干预措施: VVD-133214
疾病 / 适应症: Advanced Solid Tumors
发起方: Vividion Therapeutics, Inc.
入组人数: 295
试验地点: 48
主要终点: Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验相关资讯

概览

简要总结

This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of VVD-133214 monotherapy, and in combination with pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. VVD-133214 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, VVD-133214 may be able to block the growth of these types of cancer.

注册库

clinicaltrials.gov

开始日期

2024年1月25日

结束日期

2027年5月31日

最后更新

2个月前

研究类型

Interventional

研究设计

Sequential

性别

All

研究者

发起方

Vividion Therapeutics, Inc.

责任方

Sponsor

入排标准

入选标准

•Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
•Have a microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor; for the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic colorectal adenocarcinoma (CRC) with no prior systemic treatment for metastatic disease and not amenable to surgery
•Have received and then progressed following, or are intolerant to, standard therapy in the advanced setting
•Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
•Life expectancy of at least (≥)12 weeks
•Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for submission to Sponsor/central laboratory for retrospective central testing; for participants without archival tissue, a biopsy from either primary or metastatic tumor lesion, deemed medically feasible, must be taken
•Adequate hematologic, end-organ, and cardiovascular function, as defined in the protocol

排除标准

•Inability or unwillingness to swallow pills
•Malabsorption syndrome or other condition that would interfere with enteral absorption
•Known hypersensitivity or intolerance to ingredients from the study drug formulation including patients with rare genetic disorders such as galactosaemia, glucose-galactose intolerance or congenital lactase deficiency
•Known uncontrolled central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous meningitis
•Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis and atypical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds), or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 2 weeks prior to the start of drug administration (related to the completion of the course of antibiotics, except if for tumor fever) or 6 months for any intracranial abscess
•Has a positive test at screening for hepatitis B virus, hepatitis C virus, or for human immodeficiency virus (HIV), per local diagnostic standard and in accordance with local laws and regulations
•Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined as a screening hemoglobin A1c \<8% and no urinary ketoacidosis)
•Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
•Alcohol or drug dependence or abuse
•Patients with known Werner (WRN) syndrome

研究组 & 干预措施

VVD-133214 Dose Escalation

干预措施: VVD-133214

VVD-133214 Monotherapy Expansion

干预措施: VVD-133214

VVD-133214 + Pembrolizumab Expansion

干预措施: VVD-133214

VVD-133214 + Pembrolizumab Expansion

干预措施: Pembrolizumab

结局指标

主要结局

Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)

时间窗: From first dose of study drug(s) until 30 days after the final dose of VVD-133214 or 90 days after last dose of pembrolizumab

Incidence of Dose-Limiting Toxicities

时间窗: Cycle 1 (1 cycle is 3 weeks)

次要结局

Volume of Distribution (V/F) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Progression-Free Survival, as Assessed by the Investigator(From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months))
Overall Survival(From start of study treatment to the time of death from any cause (up to approximately 36 months))
Maximum Plasma Concentration Observed (Cmax) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Time of Maximum Plasma Concentration Observed (Tmax) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Area Under the Plasma Concentration-Time Curve (AUC) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Apparent Oral Clearance (CL/F) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Terminal Half-Life (T1/2) of VVD-133214(At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months))
Objective Response Rate(From start of study treatment until end of follow-up (up to approximately 36 months))
Disease Control Rate(From start of study treatment until end of follow-up (up to approximately 36 months))
Duration of Response(From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months))