Axatilimab + Ruxolitinib for Myelofibrosis and CMML

Overseen By Naveen Pemmaraju, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: JAK inhibitors

Must not be taking: CSF1-R inhibitors

Disqualifiers: Active infections, Tuberculosis, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for people with myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). The researchers aim to determine the best dose of axatilimab, both alone and with ruxolitinib, to assess if this combination can effectively manage these conditions. Participants should have previously tried other treatments for MF or CMML without success. This study targets those dealing with symptoms and challenges from these specific blood disorders. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot be on other investigational agents or certain treatments close to starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating how axatilimab, alone or with ruxolitinib, can determine the best dose and ensure safety for treating myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). Previous studies have shown that axatilimab is generally well-tolerated by patients. It has also been tested in other conditions, such as chronic graft-versus-host disease (GVHD), where it provided benefits when combined with other treatments.

Ruxolitinib is already used to treat myelofibrosis and is usually well-tolerated, though it can cause side effects like low blood counts or infections. These ongoing studies aim to assess the safety of axatilimab when used with ruxolitinib and to identify the optimal dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Axatilimab and Ruxolitinib for myelofibrosis and CMML because they offer a fresh approach to treatment. Unlike standard therapies that primarily target the Janus kinase (JAK) pathways, Axatilimab works by inhibiting the colony-stimulating factor 1 receptor (CSF1R), potentially reducing fibrosis and inflammation. This new mechanism of action could provide benefits beyond what current JAK inhibitors offer, addressing unmet needs in these conditions. Additionally, the potential to combine Axatilimab with Ruxolitinib could enhance effectiveness, offering a promising new option for patients.

What evidence suggests that this trial's treatments could be effective for MF and CMML?

Research has shown that axatilimab could be a promising treatment. In patients with chronic graft-versus-host disease (cGVHD), axatilimab led to improvement in 74% of cases. Participants in this trial may receive axatilimab alone or with ruxolitinib, a drug that aids in treating blood disorders. Early studies of this combination showed a 25% improvement rate in patients who had tried many other treatments. These results suggest that this combination might also be effective for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML), which are serious blood conditions. While more research is needed, these early findings are encouraging. ^{1 6 7 8 9}

Who Is on the Research Team?

Naveen Pemmaraju, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Myelofibrosis (MF) or Chronic Myelomonocytic Leukemia (CMML), who can consent to treatment and follow contraception guidelines. They should have adequate kidney and liver function, not be pregnant or breastfeeding, and cannot have severe heart issues or active infections.

Inclusion Criteria

Ability to understand and sign a written informed consent document

I am 18 years old or older.

Signed informed consent document required

Exclusion Criteria

I am currently being treated for cancer.

I have not taken any experimental drugs or therapies within the last week.

Platelet count <50x10^9/L prior to enrollment (for specific cohorts)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Axatilimab alone or in combination with Ruxolitinib to determine safety, tolerability, and efficacy

6 cycles

IV administration every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Monitoring of adverse events and overall survival

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab
• Ruxolitinib

Trial Overview The study tests Axatilimab alone and combined with Ruxolitinib in patients with MF and CMML. It aims to determine the optimal dose of Axatilimab and assess if this combination can control these conditions effectively.

How Is the Trial Designed?

Group I: Monotherapy or Combination: Treatment with Axatilimab +/- Ruxolitinib IV Q4W Experimental Treatment 2 Interventions

Participants will self-administered approximately 12 hours apart without regard to food

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Incyte, Inc

Collaborator

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07128381

Study Details | NCT07128381 | Phase I/II Clinical Trial of ... To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825002434

Efficacy and safety of axatilimab in chronic graft-versus- ... Axatilimab demonstrates robust clinical activity in refractory cGVHD. · Overall response rate reached 65 % in clinical trials. · 64 % of patients showed ...

3. targetedonc.com targetedonc.com/view/safety-and-efficacy-results-from-agave-201-axatilimab-therapy-in-cgvhd-

Safety and Efficacy Results from AGAVE-201 (Axatilimab ... 74% overall response rate · Median time to response of 1.4-1.7 months · Median failure-free survival of approximately 11 months · Main adverse ...

4. pharmacytimes.com pharmacytimes.com/view/axatilimab-a-new-frontier-for-steroid-refractory-chronic-gvhd

Axatilimab: A New Frontier for Steroid-Refractory Chronic ... The AGAVE-201 trial showed a 74% overall response rate for axatilimab in heavily pretreated cGVHD patients.

5. ir.syndax.com ir.syndax.com/news-releases/news-release-details/syndax-announces-compelling-revuforjr-revumenib-and-niktimvotm

Syndax Announces Compelling Revuforj® (revumenib) and ... Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype ...

6. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-more-50-abstracts-accepted-presentation-2025-0

Incyte Announces More than 50 Abstracts Accepted for ... The studies are evaluating the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) and/or recommended dose(s) ...

7. withpower.com withpower.com/trial/phase-2-primary-myelofibrosis-2026-3e5a4

Axatilimab + Ruxolitinib for Myelofibrosis and CMML What is the purpose of this trial? * To find the recommended dose of axatilimab given alone and in combination with ruxolitinib in patients with MF and CMML.

8. ir.syndax.com ir.syndax.com/news-releases/news-release-details/syndax-announces-data-presentations-eha-2025-showcasing

Syndax Announces Data Presentations at EHA 2025 ... “The data being presented at EHA showcase the potential for revumenib and axatilimab to transform the treatment paradigm for patients with acute ...

9. targetedonc.com targetedonc.com/view/axatilimab-plus-ruxolitinib-belumosudil-may-yield-benefit-in-cgvhd

Axatilimab Plus Ruxolitinib/Belumosudil May Yield Benefit ... In a retrospective cohort of patients with severe chronic GVHD, combination axatilimab with other GVHD therapies led to clinical benefit.