Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as CSF-1R inhibitor, SNDX-6352, Ab969.g2, C24H23FN4O3, Anti-M-CSFR Monoclonal Antibody SNDX-6352, UCB6352, SNDX6532, INCA034176
Axatilimab · 13 trials · 22 indications
Defined for each treatment group as complete response (CR) or partial response (PR) at 6 months (Cycle 7 Day 1, 28-day cycles) in the absence of new systemic therapy for cGVHD. Responses defined by the 2014 NIH consensus criteria.
Defined from the date of randomization to the date of any predefined event, whichever occurs first.
ORR was defined as the percentage of participants with a physician-assessed complete response (CR) or a physician-assessed partial response (PR), evaluated as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host disease (cGVHD). A participant was considered an objective responder if they had an overall response of CR or PR at any timepoint up to the beginning of Cycle 7. CR was defined as the 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.
The proportion of patients with confirmed PR or CR per RECIST v1.1, assessed from the start of study treatment (defined as from first dose of pembrolizumab) for up to two years. ORR in the non-targeted, unirradiated lesion(s) as defined by CR or PR per iRECIST. Objective response will be assessed separately in all sites that are not irradiated.
Defined as a best response of CR or PR in the first 6 months (up to and including Cycle 7 Day 1) in the absence of new systemic therapy for cGVHD.
Best overall response rate (ORR) will be reported as the percentage of participants who achieve partial response (PR) or a complete response (CR) to study therapy, as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host disease (cGVHD) while on study treatment.
Defined as Complete Response (CR) or Partial Response (PR) at 6 months in the absence of new systemic therapy for cGVHD. Response assessment will be based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.
The proportion of patients with absence of invasive disease in the breast and lymph nodes at the time of SOC curative-intent treatment.
evaluate the efficacy of combination of Axatilimab (SNDX-6352) and Nivolumab in the study population
Defined as adverse events reported for the first time or worsening of a pre-existing event, occurring after the first dose.
The overall response rate will be assessed by the number of participants with objective response by Cycle 7 (28-day cycles), Day 1, with responses defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.
MTD is determined by Bayesian optimal interval (BOIN) design, where the target toxicity rate for the MTD is 0.25 and the maximum sample size is 20.
If the MTD is identified as 3mg/kg, we will complete enrollment of 10 pts at the 1 mg/kg dose level, to determine if there is biological effectiveness (and clinical efficacy) at the lower dose level.
Includes hematologic and non-hematologic toxicities
The number of participants whose best response (according to the 2006 International Working Group response criteria) over the efficacy analysis period is a complete response or partial response will be tallied to estimate the overall response rate and provide a 95% exact confidence interval, according to the Clopper-Pearson method.
Will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (version 5.0).
Defined as percentage of participants with complete response or partial response confirmed by scans at least 4 weeks apart, or stable disease for \> 4 months. Will be reported with exact 95% confidence interval.
| Arm | Type | Description |
|---|---|---|
| Axatilimab | EXPERIMENTAL | Axatilimab at the protocol-defined dose. |
| Best available Treatment (BAT) | EXPERIMENTAL | Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. |
| Axatilimab + Corticosteroids | EXPERIMENTAL | Axatilimab and Corticosteroids at the protocol-defined dose. |
| Placebo + Corticosteroids | EXPERIMENTAL | Matching placebo and Corticosteroids at the protocol-defined dose. |
| Axatilimab Dose | EXPERIMENTAL | Axatilimab at the protocol-defined dose. |
| Pembrolizumab, Radiotherapy, Axatilimab | EXPERIMENTAL | Pembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. Radiotherapy, 8 Gy x 3 fractions over 3 consecutive days at C1D8/Week 2; Axatilimab (SNDX-6352; INCA034176), 1 mg/kg, IV, Q2W starting 1 week post- RT C1D15/Week 3 until disease progression or treatment intolerance. |
| Axatilimab in combination with ECP Group | EXPERIMENTAL | Participants in this group will receive Axatilimab in combination with extracorporeal photopheresis (ECP) therapy for up to seven (7) four-week cycles. Total participation duration is about 15 months. |
| Treatment Group A | EXPERIMENTAL | Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose. |
| Treatment Group B | EXPERIMENTAL | Ruxolitinib will be administered at a protocol defined starting dose. |
| Treatment Group C | EXPERIMENTAL | Corticosteroids alone will be administered at a protocol defined starting dose. |
| Pembrolizumab with Radiation Therapy and Axatilimab | EXPERIMENTAL | - |
| Treatment: All Patients | EXPERIMENTAL | Nivolumab 480 mg IV Q4 weeks Axatilimab (SNDX 6532) dose (3mg/kg IV) Q4 weeks. If DLT criteria are met, Axatilimab dosing will be reduced to 2mg/kg IV Q4W for the remainder of patients on the study. The combination will be continued until progression/toxicity up to a maximum of 12 cycles. |
| Part 1 Safety Evaluation | EXPERIMENTAL | Axatilimab at the protocol-defined dose. |
| Part 2 Efficacy Evaluation | EXPERIMENTAL | Axatilimab at the protocol-defined dose. |
| Axatilimab + Olaparib | EXPERIMENTAL | A Bayesian Optimal Interval design will be used to establish the maximum tolerated dose of Axatilimab. Dose reduction and escalation will be per protocol. Participants will complete: * Baseline visit, tumor biopsy, and imaging * Imaging every 8 weeks * Window Phase: --Predetermined dose of Olaparib 2x daily, taken 12 hours apart for 14 days * Combination Treatment Phase: * Cycle 1 through Cycle 2: * Day 1 of 28 day cycle: Tumor biopsy * Days 1 and 15 of 28 day Cycle: Predetermined dose of Axalitimab 1x daily * Days 1 through 28 of 28 day cycle Predetermined dose of Olaparib 2x daily, 12 hours apart * Tumor biopsy after two weeks of Olaparib and at the end of Cycle 2 * Cycle 3 through End of Treatment: * Days 1 and 15 of 28 Day Cycle: Predetermined dose of Axalitimab 1x daily * Predetermined dose of Olaparib 2x daily, taken 12 hours apart * End of Treatment Visit with imaging * Follow Up: Every 6 months for 3 years. Imaging will be every 10 weeks. |
| Phase I (Axatilimab) | EXPERIMENTAL | Patients receive axatilimab IV over 30 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At time of phase Ib completion, patients with clinical improvement may transition to phase II. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. |
| Phase II (Axatilimab and azacitidine) | EXPERIMENTAL | Patients receive axatilimab IV over 30 minutes on days 1 and 15 and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve PR or better may continue for up to 24 total cycles. Patients who achieve less than PR receive 2 additional cycles and, if PR or better is achieved, may complete up to 24 total cycles. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study. |
| Treatment (axatilimab, retifanlimab, paclitaxel) | EXPERIMENTAL | Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study. |
| Name | Type | Description |
|---|---|---|
| INCA034176 | DRUG | IV infusion |
| Best Available Therapy (BAT) | DRUG | Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. |
| Placebo | DRUG | IV infusion |
| Corticosteroids | DRUG | Oral/IV Infusion |
| Pembrolizumab | DRUG | Pembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. |
| Radiotherapy | RADIATION | RT, 8 Gy x 3 fractions over 3 consecutive days at C1D8/Week 2; |
| Axatilimab | DRUG | Axatilimab (SNDX-6352; INCA034176), 1 mg/kg, IV, Q2W starting 1 week post- RT C1D15/Week 3 until disease progression or treatment intolerance. |
| Best available Treatment (BAT) | DRUG | Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. |
| Extracorporeal Photopheresis | PROCEDURE | Mandatory ECP therapy will be administered at a frequency of two treatment sessions per week during Cycles 1 through 3, two treatment bi-weekly during Cycles 4 through 6, and two treatments during week 1 of Cycle 7. Optional ECP therapy will be administered at a frequency of two treatment sessions during weeks 2 and 4 of Cycles 4 through 6, when mandatory ECP is not administered. Optional ECP therapy will also be administered as two treatment sessions during week 3 of Cycle 7. After Cycle 7, participants may receive ECP therapy only at the Investigator's discretion for a maximum Treatment Period of 12 months. |
| Ruxolitinib | DRUG | Ruxolitinib will be administered at protocol defined dose. |
| Radiation Therapy | RADIATION | Radiation therapy (RT) consists of 8 Gy for 3 fractions over 3 consecutive days at Week 2. |
| Nivolumab | DRUG | Nivolumab is a programmed death receptor-1 (PD-1)-blocking antibody |
| Olaparib | DRUG | Inhibitor of poly ADP ribose polymerase (PARP)1-3, 100 or 150 mg tablet, taken orally per standard of care. |
| Azacitidine | DRUG | Given IV or SC |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Bone Marrow Aspiration and Biopsy | PROCEDURE | Undergo bone marrow biopsy and aspiration |
| Survey Administration | OTHER | Ancillary study |
| Biopsy | PROCEDURE | Undergo tumor biopsy |
| Computed Tomography | PROCEDURE | Undergo CT scan |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Paclitaxel | DRUG | Given IV |
| Positron Emission Tomography | PROCEDURE | Undergo PET scan |
| Retifanlimab | BIOLOGICAL | Given IV |
Inclusion Criteria: * Age ≥ 12 years at the time of signing the ICF. * Active, moderate to severe cGVHD, requiring systemic immune suppression. * Participants with refractory or recurrent cGVHD who have received at least 2 lines of systemic therapy, including corticosteroids and ruxolitinib. * Conc...
Axatilimab is an investigational monoclonal antibody being studied in oncology and chronic graft versus host disease. Research indications include triple-negative breast cancer, other breast cancers, chronic graft versus host disease, atypical chronic myeloid leukemia, Hodgkin lymphoma, and advanced malignant solid neoplasms. It is not yet approved for these uses and remains in clinical development.
Axatilimab targets CSF1R, the colony-stimulating factor 1 receptor. It is a monoclonal antibody that acts as an inhibitor of this receptor. By targeting CSF1R, the drug is designed to modulate myeloid cell activity, which is being explored in combination with other therapies across several cancer and graft versus host disease settings.
Axatilimab is being developed by Incyte Corporation, which trades on the Nasdaq under the ticker INCY. Incyte is the sponsor of the clinical trials evaluating the drug in oncology and chronic graft versus host disease indications.
Axatilimab is in Phase 1 and Phase 2 clinical development. The program includes a Phase 1 study in myeloproliferative neoplasms and a Phase 1b study in BRCA1/2 and PALB2-associated metastatic HER2-negative breast cancer, along with Phase 2 studies in triple-negative breast cancer and chronic graft versus host disease. It is investigational and not approved.
Axatilimab is being evaluated in several registered trials. These include NCT07015853 in triple-negative breast cancer, NCT06663722 in chronic graft versus host disease, NCT06523556 in advanced phase myeloproliferative neoplasms and related conditions, and NCT06488378 in BRCA1/2 and PALB2-associated metastatic HER2-negative breast cancer. All are actively recruiting or not yet recruiting.