Axatilimab + Corticosteroids for Chronic Graft-Versus-Host Disease

(AXemplify-357 Trial)

Recruiting at 117 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must be taking: Corticosteroids

Must not be taking: CNIs, mTOR inhibitors

Disqualifiers: Multiple allo-HCT, Overlap cGVHD, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new drug, axatilimab, combined with corticosteroids for treating moderate or severe chronic graft-versus-host disease (cGVHD), a condition that can occur after a stem cell transplant. Participants will receive either axatilimab with corticosteroids or a placebo with corticosteroids to determine which combination is more effective. The trial seeks individuals who have recently developed moderate or severe cGVHD and require systemic treatment (treatment affecting the whole body). Those who have had only one stem cell transplant from any donor and have not received extensive previous treatments for cGVHD may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have started certain treatments like CNIs or mTOR inhibitors within 2 weeks before the trial begins. It's best to discuss your current medications with the trial team.

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

Studies have shown that axatilimab is generally well-tolerated by patients with chronic graft-versus-host disease (cGVHD). In one study, 97% of patients experienced side effects, but only 58% had more serious ones. Importantly, only 16% of patients stopped treatment due to these side effects. This suggests that while some people may experience side effects, most can continue with the treatment.

Axatilimab has demonstrated strong results in treating cGVHD, a challenging condition to manage. For many patients, the benefits of the treatment might outweigh the risks. The safety data from trials is promising, but discussing potential risks and benefits with a doctor remains important. ^{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 chronic graft-versus-host disease (cGVHD) because it targets a specific part of the immune system differently than current treatments. Most treatments for cGVHD, like corticosteroids, primarily suppress the immune response as a whole. In contrast, axatilimab focuses on blocking the CSF-1R pathway, which plays a crucial role in immune cell activation involved in cGVHD. This targeted approach has the potential to reduce symptoms with possibly fewer side effects, offering new hope for patients who don't respond well to existing therapies.

What evidence suggests that axatilimab combined with corticosteroids could be an effective treatment for chronic graft-versus-host disease?

Research has shown that axatilimab offers promising results for treating chronic graft-versus-host disease (cGVHD). In one study, 65% of patients with hard-to-treat cGVHD responded well to the treatment. Another study found that 64% of patients experienced significant symptom relief. In this trial, participants will receive either axatilimab with corticosteroids or a placebo with corticosteroids. These findings suggest that axatilimab, when combined with corticosteroids, could effectively manage moderate to severe cGVHD. ^{1 2 3 6 7}

Who Is on the Research Team?

Albert Assad, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older who have recently been diagnosed with moderate to severe chronic graft-versus-host disease (cGVHD) after a stem cell transplant from any donor. They must need systemic therapy, have stable blood counts without growth factors, and be willing to prevent pregnancy.

Inclusion Criteria

I have had a stem cell transplant from a donor.

I am 12 years old or older.

I have a new case of severe chronic GVHD needing systemic treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axatilimab or placebo in combination with corticosteroids as initial treatment for chronic graft-versus-host disease

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Axatilimab
• Corticosteroids

Trial Overview The study compares the effectiveness of axatilimab plus corticosteroids against a placebo combined with corticosteroids in treating cGVHD as an initial treatment. Participants will randomly receive either the drug or placebo.

How Is the Trial Designed?

Group I: Placebo + Corticosteroids Experimental Treatment 2 Interventions

Matching placebo and Corticosteroids at the protocol-defined dose.

Group II: Axatilimab + Corticosteroids Experimental Treatment 2 Interventions

Axatilimab and Corticosteroids at the protocol-defined dose.

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?

Incyte Corporation

Lead 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

Published Research Related to This Trial

In a survey of 1377 allogeneic hematopoietic cell transplant survivors, those with moderate to severe chronic graft-versus-host disease reported significantly worse quality of life and higher symptom burden compared to those whose condition had resolved or who never had it.

A notable percentage (26.7-39.4%) of patients with active chronic graft-versus-host disease were unable to work due to health issues, highlighting the need for improved prevention and treatment strategies to enhance survivorship after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health status associated with chronic graft-versus-host disease. Lee, SJ., Onstad, L., Chow, EJ., et al.[2019]

In a study of 36 patients with moderate to severe steroid-refractory chronic GvHD, ruxolitinib demonstrated a 59% overall response rate at three months and 62% at six months, indicating its efficacy as a treatment option.

Ruxolitinib was well-tolerated, with no permanent discontinuations due to adverse events, and it significantly reduced the need for steroid doses, highlighting its safety profile in managing chronic GvHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience. Xue, E., Lorentino, F., Pavesi, F., 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]

Ruxolitinib, used as a treatment for chronic graft-versus-host disease (GVHD) resistant to other therapies, can cause significant skin reactions, including ulcerative lesions, as seen in an 18-year-old patient with refractory chronic cutaneous GVHD.

After discontinuing ruxolitinib due to suspected drug-related skin ulcers, the lesions fully recovered within four weeks, highlighting the importance of monitoring for adverse effects in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin ulcers caused by ruxolitinib in a patient with chronic cutaneous graft-versus-host disease. Aslan Candır, B., Yiğenoğlu, TN., Kızıl Çakar, M., et al.[2022]

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 3 trial involving 203 patients with steroid-resistant acute graft-versus-host disease (aGVHD), the addition of mesenchymal stromal cells (MSCs) to standard second-line therapy significantly improved overall response rates at day 28 (82.8% vs. 70.7%) and at day 56 (78.8% vs. 64.6%).

The MSC treatment not only enhanced efficacy but also reduced the incidence of chronic graft-versus-host disease (cGVHD) and drug-related toxicity, with no increase in tumor relapse rates, indicating that MSCs are a safe and effective second-line treatment option for aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. Zhao, K., Lin, R., Fan, Z., et al.[2022]

In a study of 15 patients with steroid-refractory chronic graft-versus-host disease, a combination of low doses of alemtuzumab and rituximab resulted in a 100% overall response rate at 30 days, with 67% achieving partial remission and 33% achieving complete remission.

While the treatment showed efficacy, 67% of patients experienced infections as adverse effects, highlighting the need for careful monitoring, although most infections were resolved quickly, except for one case that resulted in death from pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease. Gutiérrez-Aguirre, CH., Cantú-Rodríguez, OG., Borjas-Almaguer, OD., 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]

Acute graft-versus-host disease (GVHD) affects about 50% of patients after allogeneic hematopoietic cell transplant, and high-dose systemic steroids are the primary treatment, but many patients experience treatment failure.

Ruxolitinib is the first FDA-approved treatment specifically for steroid-refractory GVHD, and the review highlights various new treatments being studied, categorized by their mechanisms of action, which may offer hope for better management of this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Targeted Therapies for Acute Graft-Versus-Host Disease. Kasikis, S., Etra, A., Levine, JE.[2022]

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40675460/

Efficacy and safety of axatilimab in chronic graft-versus- ... The pooled Overall Response Rate was 58 % (95 % CI: 45-72 %). Clinically meaningful symptom improvement occurred in 64 % (95 % CI: 53-75 %). Any ...

3. 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.

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

Axatilimab in Recurrent or Refractory Chronic Graft-versus- ... The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the ...

5. 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.

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. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.3731

Exposure‐Response Relationships for Axatilimab in Patients ... A clinically meaningful reduction in cGVHD symptom burden (defined as a ≥ 7-point improvement in mLSS) in the first 6 cycles was reported by 55% ...