Axatilimab for GVHD

Recruiting at 2 trial locations

Overseen By cGVHD Intake Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Disqualifiers: Organ dysfunction, Uncontrolled psychiatric illness, Others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 31

Duration: 24 cycles (approximately 24 months)

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new treatment, axatilimab, works for individuals experiencing skin thickening and hardening due to chronic graft-versus-host disease (cGVHD) after a stem cell transplant. cGVHD can cause serious skin problems, and current treatments often lead to unwanted side effects. Axatilimab, a special type of protein, aims to reduce inflammation and prevent skin issues from worsening. Individuals who have undergone a donor stem cell transplant and are experiencing active cGVHD affecting their skin might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from a potentially effective new therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any new non-corticosteroid systemic immunosuppressive agents within 28 days before screening, unless you plan to stop them no later than 21 days after the first dose of axatilimab. You can continue taking systemic corticosteroids like prednisone at a dose of 1 mg/kg or less per day.

Is there any evidence suggesting that axatilimab is likely to be safe for humans?

Research has shown that axatilimab is generally safe for people with chronic graft-versus-host disease (cGVHD). Studies found that a low dose of axatilimab, administered every two weeks, was the easiest for patients to manage, with only about 6% needing to stop treatment due to side effects.

Higher doses caused more problems. For instance, in the group taking a 1 mg dose, 22% of patients discontinued due to side effects. However, many patients responded well to the treatment overall.

These findings suggest that axatilimab can be used safely, especially at lower doses, with fewer people experiencing serious issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for graft-versus-host disease (GVHD), which often include corticosteroids and immunosuppressants, axatilimab offers a novel approach by targeting the CSF1R pathway. This mechanism aims to reduce the activity of certain immune cells that contribute to the disease, potentially leading to fewer side effects and more effective disease control. Researchers are excited about axatilimab because it represents a new way to tackle GVHD, offering hope for patients who don't respond well to existing therapies.

What evidence suggests that axatilimab might be an effective treatment for sclerosis related to chronic graft-versus-host disease?

Research shows that axatilimab, the treatment under study in this trial, holds promise for treating chronic graft-versus-host disease (cGVHD). Studies found that 65% of patients with cGVHD who received axatilimab experienced improvements, meaning more than half felt better. Some patients also showed significant improvements in joint and connective tissue issues, with a 76% response rate. Axatilimab targets cells that cause inflammation and scarring, major issues in cGVHD. These early findings suggest that axatilimab could help manage symptoms like skin thickening and hardening. ^{3 4 6 7 8}

Who Is on the Research Team?

Stephanie J. Lee, MD, MPH

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with skin sclerosis from chronic graft-versus-host disease after a donor stem cell transplant. It's not specified who can't join, but typically those with other serious health issues or allergies to the treatment may be excluded.

Inclusion Criteria

My skin is moderately thickened or I have moderate symptoms due to chronic graft-versus-host disease.

I am using immunosuppressive drugs for sclerotic chronic GVHD and responding to them.

I was diagnosed with sclerosis less than 6 months ago.

Exclusion Criteria

I have a history of myositis.

I am taking more than 1 mg/kg/day of prednisone or its equivalent.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive axatilimab IV over 30 minutes on days 1 and 15 of cycles 1-6 and then on day 1 of remaining cycles. Cycles repeat every 28 days for up to 24 cycles.

24 cycles (approximately 24 months)

Visits on days 1 and 15 of cycles 1-6, then on day 1 of remaining cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Follow-up at 30 days post-treatment, then periodically up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab

Trial Overview The study tests axatilimab, a monoclonal antibody that targets and blocks receptors involved in inflammation and fibrosis in cGVHD. The trial includes questionnaires, skin biopsies, biospecimen collection, and skin measurements to assess effectiveness.

How Is the Trial Designed?

Group I: Treatment (axatilimab) Experimental Treatment 5 Interventions

Patients receive axatilimab IV over 30 minutes on days 1 and 15 of cycles 1-6 and then on day 1 of remaining cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Additionally, patients may undergo optional skin biopsies and optional skin flexibility assessments throughout the study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39292927/

Axatilimab in Recurrent or Refractory Chronic Graft-versus- ... The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD. Methods: In this phase 2, multinational, pivotal, ...

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. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2401537

Axatilimab in Recurrent or Refractory Chronic Graft-versus- ... The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD. Methods. In this phase 2, multinational, pivotal, ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7361/527993/Efficacy-of-Axatilimab-in-the-Management-of

Efficacy of Axatilimab in the Management of Chronic Graft ... In this systematic review, axatilimab exhibited promising therapeutic outcomes for refractory cGVHD based on the findings from Phase I and II clinical trials.

5. targetedonc.com targetedonc.com/view/agave-201-outcomes-support-low-dose-of-axatilimab-for-chronic-gvhd

AGAVE-201 Outcomes Support Low Dose of Axatilimab for ... In the joints and fascia, there was a good response rate at 76%, but similar to what we saw with belumosudil [Rezurock] there was a low CR rate.

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1/499054/Safety-and-Efficacy-of-Axatilimab-at-3-Different

Safety and Efficacy of Axatilimab at 3 Different Doses in ... Safety and efficacy of Axatilimab at 3 different doses in patients with chronic graft-versus-host disease (AGAVE-201)

7. astctjournal.org astctjournal.org/article/S2666-6367(23)01795-5/fulltext

Safety and Efficacy of Axatilimab in Patients with Chronic ... Conclusion. In AGAVE-201, the primary endpoint was met. AXA 0.3 mg/kg Q2W was well tolerated and resulted in robust clinical activity and durable responses.

8. niktimvohcp.com niktimvohcp.com/

Niktimvo™ (axatilimab-csfr) Axatilimab for chronic graft-versus-host disease after failure of at least two prior systemic therapies: results of a phase I/II study. J Clin Oncol. 2023 ...