A Phase 1 Study to Investigate Axatilimab Alone or in Combination With Durvalumab in Patients With Solid Tumors
- Conditions
- Unresectable Malignant NeoplasmMetastatic TumorLocally Advanced Malignant NeoplasmSolid Tumor
- Interventions
- Registration Number
- NCT03238027
- Lead Sponsor
- Syndax Pharmaceuticals
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Ph1a D2: 3 mg/kg Axatilimab 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. Ph1a D4: 10 mg/kg Axatilimab 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. Ph1a D3: 6 mg/kg Axatilimab 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. Ph1b D1: 1 mg/kg Axatilimab+1500 mg durvalumab Axatilimab 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. Ph1b D2: 3 mg/kg Axatilimab+1500 mg durvalumab Axatilimab 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. Ph1b D3: 6 mg/kg Axatilimab+1500 mg durvalumab Axatilimab 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. Ph1a D1: 1 mg/kg Axatilimab 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. Ph1b D3: 6 mg/kg Axatilimab+1500 mg durvalumab 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. Ph1b D1: 1 mg/kg Axatilimab+1500 mg durvalumab 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. Ph1b D2: 3 mg/kg Axatilimab+1500 mg durvalumab 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.
- Primary Outcome Measures
Name Time Method Phase 1b: Determination of Recommended Phase 2 dose (RP2D) of Axatilimab when given in combination with a fixed dose of durvalumab 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 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 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 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 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 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.
- Secondary Outcome Measures
Name Time Method 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) Cmax for SDNX-6352 for axatilimab will be computed.
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) To determine if the size and number of target lesions changes in response to treatment with axatilimab by analyzing CT-Scans/MRIs per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and irRECIST.
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) Cmax for axatilimab will be computed.
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) T1/2 for axatilimab will be computed.
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) AUC for SDNX-6352 for axatilimab will be computed.
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) Tmax for SDNX-6352 for axatilimab will be computed.
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) AUC for durvalumab will be computed.
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) Tmax for durvalumab will be computed.
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) T1/2 for durvalumab will be computed.
Phase 1b: Evaluation of the immunogenicity of Axatilimab Approximately 6 months (from first dose to End of Treatment visit) To assess the immunogenicity of axatilimab as measured by presence of anti-drug antibodies (ADA)
Phase 1a: Effect of Axatilimab on CSF-1 and IL-34 Approximately 6 months (from first dose to End of Treatment visit) To assess change from Baseline in plasma CSF-1 and IL-34 following IV administration
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) AUC for axatilimab will be computed.
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) Cmax for durvalumab will be computed.
Phase 1a: Evaluate the immunogenicity of Axatilimab Approximately 6 months (from first dose to End of Treatment visit) To assess the immunogenicity of axatilimab as measured by presence of anti-drug antibodies (ADA)
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) T1/2 for SDNX-6352 for axatilimab will be computed.
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) Tmax for axatilimab will be computed.
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) To determine if the size and number of target lesions changes in response to treatment with axatilimab by analyzing CT-Scans/MRIs per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and irRECIST.
Phase 1b: Evaluation of the immunogenicity of durvalumab Approximately 6 months (from first dose to End of Treatment visit) To assess the immunogenicity of durvalumab as measured by presence of anti-drug antibodies (ADA)
Phase 1b: Effect of Axatilimab on CSF-1 and IL-34 Approximately 6 months (from first dose to End of Treatment visit) To assess change from Baseline in plasma CSF-1 and IL-34 following IV administration
Trial Locations
- Locations (5)
Honor Health
🇺🇸Scottsdale, Arizona, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States