Axatilimab for Graft-versus-Host Disease

(AGAVE-201 Trial)

Recruiting at 124 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

241 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Axatilimab for treating graft-versus-host disease?

Research shows that Axatilimab, a drug that blocks certain signals in the body, can help reduce chronic graft-versus-host disease by targeting specific cells that contribute to the condition. This was observed in a study where Axatilimab was used after other treatments had failed. ^{1 2 3 4 5}

Is Axatilimab safe for humans?

Axatilimab has been studied in a Phase I/II trial for chronic graft-versus-host disease, and it is a humanized monoclonal antibody that targets specific immune cells. While the study focused on its effectiveness, the trial's completion suggests it was considered safe enough to proceed through these phases. ^{5 6 7 8 9}

What makes the drug Axatilimab unique for treating graft-versus-host disease?

Axatilimab is unique because it is a humanized monoclonal antibody that targets and inhibits the colony-stimulating factor 1 receptor (CSF-1R), which helps reduce the development of macrophages that contribute to chronic graft-versus-host disease (cGVHD) fibrosis. This mechanism of action is different from other treatments that focus on T-cell modulation. ^{5 7 10 11 12}

What is the purpose of this trial?

This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.

Research Team

Vedran Radojcic, M.D.

Principal Investigator

Syndax Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with steroid-refractory acute graft-versus-host disease. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Adoptive transfer of allogeneic regulatory T cells into patients with chronic graft-versus-host disease. [2021]

3. England pubmed.ncbi.nlm.nih.gov

HLA-A*02:01-directed chimeric antigen receptor/forkhead box P3-engineered CD4+ T cells adopt a regulatory phenotype and suppress established graft-versus-host disease. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Treatment of severe intestinal acute graft-versus-host disease with CD25 monoclonal antibody in haploidentical hematopoietic stem cell transplantation]. [2018]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Vedolizumab for acute gastrointestinal graft-versus-host disease: A systematic review and meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Bortezomib modulates regulatory T cell subpopulations in the process of acute graft-versus-host disease. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2023]