Axatilimab for Graft-versus-Host Disease

(AGAVE-201 Trial)

Not currently recruiting at 139 trial locations

Overseen By Tim O'Toole

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Syndax Pharmaceuticals

Must be taking: Corticosteroids, CNI, mTOR inhibitors

Must not be taking: CSF1-R therapies

Disqualifiers: AIDS, Hepatitis B, Hepatitis C, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests axatilimab's effectiveness in treating chronic graft-versus-host disease (cGVHD), a condition that can occur after stem cell transplants when donor cells attack the body. The study explores three different dose levels of axatilimab to assess its effectiveness and safety. Individuals with active cGVHD symptoms, despite trying at least two different treatments, might be suitable for this trial. Participants will receive axatilimab through an IV every few weeks for up to two years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

You may need to stop taking some of your current medications. If you're on treatments for cGVHD other than corticosteroids, CNI, or mTOR inhibitors, you'll need a washout period (time without taking certain medications) of 2 weeks or 5 half-lives, whichever is shorter, before joining the study.

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

Research has shown that axatilimab has been tested for safety in people with chronic graft-versus-host disease (cGVHD). One study found that the 0.3 mg/kg dose of axatilimab was generally well tolerated. However, higher doses led to more side effects. Specifically, 6% of participants stopped treatment with the 0.3 mg/kg dose due to side effects, while 22% stopped at the 1 mg/kg dose.

This indicates that while axatilimab appears promising, the risk of side effects may increase with higher doses. Overall, earlier studies suggest axatilimab can be a safe option at lower doses for cGVHD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic graft versus host disease?

Researchers are excited about axatilimab for treating graft-versus-host disease (GVHD) because it offers a novel approach compared to current treatments like corticosteroids and immunosuppressants. Axatilimab is unique because it targets the CSF-1 receptor, which is involved in the inflammatory process of GVHD, potentially leading to a more direct and effective control of symptoms. Additionally, axatilimab is administered intravenously, with varying dosages and frequencies being tested, offering flexibility in how it might be integrated into patient care. This targeted mechanism and flexible administration have the potential to improve outcomes for patients who may not respond well to existing therapies.

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

Research has shown that axatilimab may help treat chronic graft-versus-host disease (cGVHD). Studies found that 65% of patients with difficult-to-treat cGVHD responded to this treatment. Axatilimab works by blocking a specific receptor involved in the disease. The treatment was well-tolerated, meaning it did not cause serious side effects. In this trial, participants will join different dose cohorts of axatilimab to further evaluate its effectiveness and safety. These findings suggest axatilimab could be a good option for patients who have not responded to other treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Vedran Radojcic, M.D.

Principal Investigator

Syndax Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people aged 2 or older with chronic graft versus host disease (cGVHD) who've had at least two prior systemic therapies. They must have a certain level of physical function, adequate organ and bone marrow function, and not be pregnant or breastfeeding. Participants can't join if they're on other cGVHD treatments besides corticosteroids/CNI/mTOR inhibitors, in another study, have been exposed to CSF1-R targeted therapies, or have severe illnesses.

Inclusion Criteria

I can care for myself but may not be able to do active work or play.

My organs and bone marrow are functioning well.

I had a stem cell transplant and need treatment for ongoing graft-versus-host disease.

Exclusion Criteria

I haven't had any cancer other than the one I'm seeking treatment for in the last 3 years, or if I have, it was treated with the intent to cure and is approved by the study's medical team.

I am not taking any cGVHD treatments other than steroids, CNI, or mTOR inhibitors.

Receiving another investigational treatment within 28 days of randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axatilimab at 3 different doses in 28-day treatment cycles

Up to 2 years

Every 2 or 4 weeks depending on dose cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab

Trial Overview The study tests the effectiveness and safety of axatilimab at three different doses in patients with active cGVHD that's come back or hasn't responded to treatment after an allogeneic stem cell transplant. It's a Phase 2 trial focusing on those who've tried multiple treatments already.

How Is the Trial Designed?

Group I: Axatilimab Dose Cohort 3 Experimental Treatment 1 Intervention

Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.

Group II: Axatilimab Dose Cohort 2 Experimental Treatment 1 Intervention

Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.

Group III: Axatilimab Dose Cohort 1 Experimental Treatment 1 Intervention

Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

Who Is Running the Clinical Trial?

Syndax Pharmaceuticals

Lead Sponsor

Trials

49

Recruited

2,700+

Published Research Related to This Trial

A new method for isolating and expanding regulatory T cells (Treg) from donors was successfully developed, resulting in high-purity Treg preparations that were transfused into five patients with chronic graft-versus-host disease (cGvHD).

Two out of five patients showed clinical improvement in cGvHD symptoms after Treg transfusion, while three maintained stable symptoms for up to 21 months, indicating potential efficacy; however, there were also risks, as two patients developed skin cancers months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease. Theil, A., Tuve, S., Oelschlägel, U., et al.[2021]

In a phase 1 clinical trial involving 16 patients with steroid-refractory chronic graft-versus-host disease (SR-cGVHD), the immunomodulatory drug abatacept was found to be safe and well-tolerated, with no dose-limiting toxicities reported.

Abatacept led to a 44% clinical partial response rate and a significant 51.3% reduction in prednisone usage among responders, indicating its potential as an effective treatment option for SR-cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Nahas, MR., Soiffer, RJ., Kim, HT., et al.[2021]

In a phase 2 study involving 36 patients with steroid-refractory chronic graft-versus-host disease (cGVHD), abatacept demonstrated an overall response rate of 58%, with all responders achieving a partial response, indicating its efficacy as a treatment option.

Abatacept was well tolerated, showing few serious infections, and it positively impacted the immune system by reducing levels of inflammatory markers like IL-1α and TNF-α, suggesting it modifies the immune microenvironment in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Koshy, AG., Kim, HT., Liegel, J., et al.[2023]

Axatilimab, a monoclonal antibody targeting CSF-1R, shows promise in treating chronic graft-versus-host disease (cGVHD) with a 50% overall response rate after 7 treatment cycles in a phase II study involving 23 patients, and an 82% response rate in the first six cycles.

The treatment demonstrated a favorable safety profile, with manageable adverse effects primarily related to on-target CSF-1R inhibition, and no cases of cytomegalovirus reactivation, indicating its potential as a safe option for patients with refractory cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. Kitko, CL., Arora, M., DeFilipp, Z., et al.[2023]

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

Safety and Efficacy of Axatilimab in Patients with Chronic ... 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.

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. onclive.com onclive.com/view/safety-and-efficacy-of-axatilimab-at-3-different-doses-in-patients-with-chronic-graft-versus-host-disease-agave-201-

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). Author(s)Karolina Faysman ...