A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-806 in Participants With KRAS G12D Mutated Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Arvinas Inc.
- 入组人数
- 159
- 试验地点
- 15
- 主要终点
- Part A (Phase 1): Number of dose-limiting toxicities of ARV-806
研究概览
简要总结
This is a study to evaluate the safety and potential anti-tumor activity of an investigational agent called ARV-806 in Adults with Advanced Cancer having a specific Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. This is an open-label study which means that participants and study staff will know that all participants will receive ARV-806.
Researchers think that ARV-806 can work by breaking down a specific protein with a mutation that is present in some tumors, which might help prevent or slow tumors from growing. This will be the first time ARV-806 will be used in people. The investigational drug will be given through a vein. This is called intravenous (IV) infusion.
This study will include 2 parts:
In Part A (Phase 1), different small groups of participants will receive lower to higher doses of ARV-806. Adults with advanced cancers having a specific KRAS mutation will be included.
In Part B (Phase 2), participants will be assigned to receive one of up to 2 dose levels decided by the information from Part A. Part B will include participants with advanced pancreatic ductal cancer having a specific KRAS mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological diagnosis of unresectable or metastatic solid tumor malignancy, AND
- •Must have evidence of KRAS G12D mutation in tumor tissue or blood (circulating tumor deoxyribonucleic acid [ctDNA]), AND
- •Must have received prior standard-of-care (SOC) therapy appropriate for their type and stage of disease and have no other available treatment options with curative intent, or, in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy, AND
- •Must have at least 1 measurable lesion
- •Histological or cytological diagnosis of unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D mutation status confirmed by local testing of tumor tissue using a validated molecular or next-generation sequencing (NGS) testing, AND
- •Must be willing to provide archival tumor tissue or willing to undergo pretreatment biopsy, AND
- •Must have received at least one prior standard of care systemic therapy for PDAC (systemic therapy received in the neoadjuvant or adjuvant setting is allowed), AND
- •Participants must have at least 1 measurable lesion
- •Part A / Part B:
- •Eastern Cooperative Oncology Group performance status of 0 or 1,
- •Participants with adequate organ function,
- •Participants must accept and follow pregnancy prevention guidance.
排除标准
- •Part A / Part B:
- •Active brain metastases
- •Carcinomatous meningitis
- •Uncontrolled hypertension despite optimal medical therapy
- •Prior treatment with a KRAS G12D or a KRAS G12C targeting therapy (pan-KRAS inhibitor/degrader included)
- •Participants with an inability to comply with listed prohibited treatments
- •Systemic anticancer therapy within 2 weeks or 5 half-lives (whichever is shorter) or radiation therapy (excluding palliative radiation) within 2 weeks prior to the study intervention treatment. If the last immediate anticancer treatment contained an antibody-based agent(s), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) is required prior to receiving the study intervention treatment.
- •Standard 12-lead electrocardiogram that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
研究组 & 干预措施
Phase 1/Part A Monotherapy (Dose Escalation)
Participants will receive ARV-806 at the assigned doses and regimen (weekly or every 2 weeks).
干预措施: ARV-806 (Drug)
Phase 2/Part B Monotherapy (Dose Expansion)
Participants will receive ARV-806 at one of up to 2 dose levels/regimens selected from Part A)
干预措施: ARV-806 (Drug)
结局指标
主要结局
Part A (Phase 1): Number of dose-limiting toxicities of ARV-806
时间窗: 28 days from first ARV-806 administration
Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (28 days).
Part B (Phase 2): Overall Response Rate (ORR)
时间窗: Approximately 2 years
ORR is a parameter measuring the anti-tumor activity of ARV-806. ORR is the percentage of participants for whom the study treatment resulted in a complete response or partial response of the disease under study. It is measured using CT/MRI and RECIST 1.1 criteria per investigator assessment.
Part A (Phase 1): Number of participants with AEs
时间窗: From the study baseline to at least 28 days after last dose of ARV-806
AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability
Part B (Phase 2): Overall Response Rate (ORR)
时间窗: Approximately 2 years
ORR is a parameter measuring the anti-tumor activity of ARV-806. ORR is the percentage of participants for whom the study treatment resulted in a complete response or partial response of the disease under study. It is measured using CT/MRI and RECIST 1.1 criteria per investigator assessment.
Part A (Phase 1): Number of dose-limiting toxicities (DLTs) of ARV-806
时间窗: 28 days from first ARV-806 administration
Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (28 days).
次要结局
- PK of ARV-806 (Part A): Time for Cmax (Tmax)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- Part B: ARV-806 whole blood pre and post dose concentration(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUCtau)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- PK of ARV-806 (Part A): Area under the plasma or blood concentration time profile from time zero to the time of the last quantifiable concentration (Clast) (AUClast)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- PK of ARV-806 (Part A): Minimum observed concentration (Cmin)(Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- PK of ARV-806 (Part A): Plasma or blood clearance (CL)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUC0-tau)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.)
- PK of ARV-806 (Part A): Area under the plasma or blood concentration time profile from time zero to the time of the last quantifiable concentration (Clast) (AUC0-last)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.)
- PK of ARV-806 (Part A): Minimum observed concentration (Cmin)(Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.)
- PK of ARV-806 (Part A): Plasma or blood clearance (CL)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.)
- PK of ARV-806 (Part A): Time for Cmax (Tmax)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.)
- PK of ARV-806 (Part A): Volume of distribution (Vd)(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- Part A: Overall Response Rate (ORR)(Approximately 2 years)
- Part A: Time to Response (TTR)(Approximately 2 years)
- Part A: Duration of Response (DOR)(Approximately 2 years)
- Part A: Disease Control Rate (DCR)(Approximately 2 years)
- Part B: Number of participants with AEs(From the study baseline to at least 28 days after last dose of ARV-806)
- Part B: ARV-806 whole blood pre-dose concentration(At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806)
- Part B: Time to Response (TTR)(Approximately 2 years)
- Part B: Duration of Response (DOR)(Approximately 2 years)
- Part B: Disease Control Rate (DCR)(Approximately 2 years)