A Phase 1, Open-Label, Dose Escalation Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of SNDX-6352 Monotherapy and SNDX-6352 in Combination With Durvalumab in Patients With Unresectable, Recurrent, Locally-Advanced, or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 5
- 主要终点
- Phase 1b: Determination of Recommended Phase 2 dose (RP2D) of Axatilimab when given in combination with a fixed dose of durvalumab
研究概览
简要总结
A Phase 1 dose escalation study to determine if axatilimab as monotherapy and axatilimab in combination with a fixed dose of durvalumab will be sufficiently safe and well-tolerated at biologically active doses to warrant further investigation in patients with solid tumors.
详细描述
This is an open label, multi-center Phase 1 study consisting of Phase 1a and Phase 1b. The study will evaluate axatilimab monotherapy (in Phase 1a) and axatilimab combined with durvalumab (in Phase 1b) in patients with advanced solid tumors which must have progressed following prior treatment and have no standard therapy alternatives left (i.e., patients must not be candidates for regimens known to provide clinical benefit). The primary objective will be to determine the MTD and/or RP2D of axatilimab as monotherapy (Phase 1a) and in combination with durvalumab (Phase 1b) as evaluated by the incidence of AEs that are defined as DLTs. In both study phases, a standard "3+3" dose escalation schema will be used to determine an MTD with 3-6 evaluable patients enrolled per dose level. The RP2D will be determined based on data from the dose escalation patients as reviewed by the Safety Review Committee (SRC; comprised of investigators and the Sponsor).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ph1a D1: 1 mg/kg Axatilimab
Three (3) patients receive starting dose of 1 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1a D2: 3 mg/kg Axatilimab
Three (3) patients receive next higher dose of 3 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1a D3: 6 mg/kg Axatilimab
Three (3) patients receive next higher dose of 6 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1a D4: 10 mg/kg Axatilimab
Three (3) patients receive next higher dose of 10 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1b D1: 1 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive starting dose of 1 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee. If 1 DLT is observed in 1 of 3 patients, then 3 additional patients will be treated at the 1 mg/kg axatilimab dose level; if none of the 3 additional patients experience a DLT (i.e. 1 of 6), the dose will be escalated to an intermediate dose of 2 mg/kg. Escalation from 2 mg/kg to 3 mg/kg will follow the general dose escalation rules described above for both study phases.
干预措施: Axatilimab (Drug)
Ph1b D1: 1 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive starting dose of 1 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee. If 1 DLT is observed in 1 of 3 patients, then 3 additional patients will be treated at the 1 mg/kg axatilimab dose level; if none of the 3 additional patients experience a DLT (i.e. 1 of 6), the dose will be escalated to an intermediate dose of 2 mg/kg. Escalation from 2 mg/kg to 3 mg/kg will follow the general dose escalation rules described above for both study phases.
干预措施: Durvalumab (Drug)
Ph1b D2: 3 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive next higher dose of 3 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1b D2: 3 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive next higher dose of 3 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Durvalumab (Drug)
Ph1b D3: 6 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive next higher dose of 6 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Axatilimab (Drug)
Ph1b D3: 6 mg/kg Axatilimab+1500 mg durvalumab
Three (3) patients receive next higher dose of 6 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Phase 1b: Determination of Recommended Phase 2 dose (RP2D) of Axatilimab when given in combination with a fixed dose of durvalumab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.
Phase 1a: Determination of Recommended Phase 2 dose (RP2D) of Axatilimab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.
Phase 1b: Determination of any Dose limiting toxicities (DLT)s of Axatilimab when given in combination with a fixed dose of durvalumab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.
Phase 1a: Determination of Maximum tolerable dose (MTD) of Axatilimab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.
Phase 1a: Determination of any Dose limiting toxicities (DLT)s of Axatilimab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.
Phase 1b: Determination of Maximum tolerable dose (MTD) of Axatilimab when given in combination with a fixed dose of durvalumab
时间窗: Approximately 9 months (from first dose to 90-day follow-up post-last dose)
All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.
次要结局
- Phase 1a: PK endpoint of Cmax (maximum observed concentration) for Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: Evaluation of preliminary anti-tumor activity of Axatilimab on solid tumors(Approximately 9 months (from baseline scan to 90-day follow-up post-last dose))
- Phase 1b: PK endpoint of Cmax (maximum observed concentration) for Axatilimab when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of T1/2 (apparent terminal elimination half-life)) for Axatilimab when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: PK endpoint of AUC (area under the curve) for Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: PK endpoint of Tmax (time to reach maximum observed concentration) for Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of AUC (area under the curve) for durvalumab when given in combination with Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of Tmax (time to reach maximum observed concentration) for durvalumab when given in combination with Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of T1/2 (apparent terminal elimination half-life) for durvalumab when given in combination with Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: Evaluation of the immunogenicity of Axatilimab(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: Effect of Axatilimab on CSF-1 and IL-34(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of AUC (area under the curve) for Axatilimab when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of Cmax (maximum observed concentration) for durvalumab when given in combination with Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: Evaluate the immunogenicity of Axatilimab(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1a: PK endpoint of T1/2 (apparent terminal elimination half life)) for Axatilimab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: PK endpoint of Tmax (time to reach maximum observed concentration) for Axatilimab when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups.(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: Evaluation of preliminary anti-tumor activity of Axatilimab when given in combination with a fixed dose of durvalumab on solid tumors.(Approximately 9 months (from baseline scan to 90-day follow-up post-last dose))
- Phase 1b: Evaluation of the immunogenicity of durvalumab(Approximately 6 months (from first dose to End of Treatment visit))
- Phase 1b: Effect of Axatilimab on CSF-1 and IL-34(Approximately 6 months (from first dose to End of Treatment visit))