Approval Probability
TA Base Rate
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ML Risk
Label indication NIKTIMVO is indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. NIKTIMVO is a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in… FDA label
Also known as Niktimvo, SNDX-6352
Axatilimab · 4 trials · 6 indications
The ORR was defined as the percentage of participants with objective response (complete response \[CR\] or partial response \[PR\]). CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site.
A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.
The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease \[cGVHD\] and pharmacokinetic/pharmacodynamic effects).
CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.
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.
All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.
All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Axatilimab | EXPERIMENTAL | Participants will receive axatilimab every 2 weeks during the 26-week Treatment Period. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo every 2 weeks during the 26-week Treatment Period. |
| Axatilimab Dose Cohort 1 | EXPERIMENTAL | Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years. |
| Axatilimab Dose Cohort 2 | EXPERIMENTAL | Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years. |
| Axatilimab Dose Cohort 3 | EXPERIMENTAL | Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years. |
| Cohorts of escalating dose levels of axatilimab | EXPERIMENTAL | Escalating dose levels of axatilimab to establish the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D). Intravenous (IV) infusion; axatilimab at a dose of 0.15 milligrams (mg)/kilogram (kg) to 3 mg/kg. |
| Phase 2 Dose Expansion | EXPERIMENTAL | Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample size. IV infusion; axatilimab at a dose of 1 mg/kg. |
| Ph1a D1: 1 mg/kg Axatilimab | EXPERIMENTAL | 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. |
| Ph1a D2: 3 mg/kg Axatilimab | EXPERIMENTAL | 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 D3: 6 mg/kg Axatilimab | EXPERIMENTAL | 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. |
| Ph1a D4: 10 mg/kg Axatilimab | EXPERIMENTAL | 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. |
| Ph1b D1: 1 mg/kg Axatilimab+1500 mg durvalumab | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| Axatilimab | DRUG | Administered as intravenous (IV) infusion |
| Placebo | OTHER | Placebo to match axatilimab administered as IV infusion. Placebo will not contain active ingredient. |
| Durvalumab | DRUG | Durvalumab (MEDI4736) is a humanized IgG1 kappa mAb that blocks the interaction of PD-L1 with PD-1 CD80 (B7.1) molecules |
Key Inclusion Criteria: * Documented diagnosis of IPF per the 2018 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society Clinical Practice Guideline (Raghu 2018). * Chest high-resolution computed tomography (HRCT) perfo...
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Axatilimab is an investigational monoclonal antibody being studied for chronic graft-versus-host disease (cGVHD), idiopathic pulmonary fibrosis (IPF), and solid tumors. It is in Phase 2 development, with clinical trials in cGVHD and IPF, and earlier Phase 1 studies in solid tumors and active cGVHD. It has received a Priority Review designation from the FDA.
Axatilimab targets CSF1R, the colony-stimulating factor 1 receptor. It is an inhibitor of this receptor, which is involved in the biology of macrophages. By binding CSF1R, axatilimab is designed to modulate macrophage activity, a mechanism relevant to its study in chronic graft-versus-host disease, idiopathic pulmonary fibrosis, and solid tumors.
Axatilimab is being developed by Syndax Pharmaceuticals, Inc., which trades under the ticker SNDX. The company is running clinical trials of the monoclonal antibody in chronic graft-versus-host disease and idiopathic pulmonary fibrosis, and earlier studies in solid tumors.
Axatilimab is in Phase 2 clinical development. It is an investigational monoclonal antibody and has not been approved by the FDA. The Phase 2 program includes the MAXPIRe study in idiopathic pulmonary fibrosis and a dose-ranging study in chronic graft-versus-host disease. An earlier Phase 1/2 study in active cGVHD and a Phase 1 solid tumor study have been completed.
Axatilimab is being studied in two Phase 2 trials: NCT06132256 (MAXPIRe) in idiopathic pulmonary fibrosis, which is active but not recruiting, and NCT04710576 in chronic graft-versus-host disease, which is recruiting. Completed studies include NCT03604692, a Phase 1/2 trial in active cGVHD, and NCT03238027, a Phase 1 trial in solid tumors alone or with durvalumab.
Axatilimab is investigational and has not been approved by the FDA. It is in Phase 2 clinical development for chronic graft-versus-host disease, idiopathic pulmonary fibrosis, and solid tumors. The FDA has granted it a Priority Review designation, which is a regulatory status for review of a marketing application, not an approval.