MaaT013: Positive Phase 3 Results in Acute Graft-vs-Host Disease

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Study Design

Inclusion criteria:

  • Age ≥ 18 years old
  • Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen
  • Patients who develop aGvHD episode with GI involvement per MAGIC guidelines (=grades II to IV), with or without involvement of other organs (Harris et al. 2016)
  • Patients resistant to steroids AND either resistant to OR with intolerance to ruxolitinib (intolerant patients: who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib). The diagnosis must be confirmed within 48h prior to study pre-treatment start.

The study was conducted in 6 European countries (Austria, Belgium, France,Germany, Italy and Spain) accross 50 sites.

Read more: Clinical Trial.Gov

ARES: Strong Response to MaaT013 in aGvHD Following Steroid and Ruxolitinib Failure

  • 62% GI-ORR with high CR and VGPR rates.

  • 64% ORR indicating efficacy beyond the GI tract.

  • The 12-month probability of survival was 54% (median survival not reached).

  • The 12-month probability was significantly higher in patients who responded at Day 28 than those who did not respond (67% vs 28% respectively, p <0.0001), demonstrating MaaT013’s significant survival benefit in refractory GI-aGvHD.

  • Response-driven prolonged survival

  • 1-year probability of survival of 54% vs 15%  following best available therapy (Abedin et al. 2021).

Enrolled patients will continue to be followed for secondary and exploratory endpoints for the duration of the study.

See the press release

“The impressive results of MaaT013’s Phase 3 trial mark a transformative step forward in treating refractory GI-aGvHD. With a GI-ORR of 62% at Day 28 and an estimated 12-month survival probability of 54%, these outcomes underscore the curative role of microbiota-based therapies in achieving durable responses leading to prolonged survival. As MaaT013 gains adoption in Europe, it has the potential to redefine care standards for patients facing this life-threatening complication.”

Prof. Malard, MD, hematology professor at Saint-Antoine Hospital and Sorbonne University, lead investigator for the Phase 3 ARES trial

Definitions

  • 1SR-GI-aGvHD in ARES Study is defined as patients resistant to steroids AND either resistant to OR with intolerance to ruxolitinib (intolerant patients: who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib). SR-aGvHD includes patients administered high-dose systemic CS (methylprednisolone 2 mg/kg/day – or equivalent prednisone dose 2.5 mg/kg/day), given alone or combined with CNI or mTOR inhibitor and either:
    • Lack of improvement (i.e., no decrease in stage in at least 1 involved organ system) after ≥ 5 days of treatment with CS at 2 mg/Kg/d methylprednisolone equivalent dose, or
    • Progression (i.e., increase in any organ system or any new organ involvement) after ≥ 3 days of treatment with CS at 2 mg/Kg/d methylprednisolone equivalent dose, or
    • Patients treated with 1 mg/Kg/d of CS because the physician deemed that they would not tolerate 2 mg/Kg/d and who correspond to the definition of SR patients, or
    • Patients who previously began CS therapy at a lower dose (at least 1 mg/Kg/d methylprednisolone equivalent) but develop new GvHD in another organ system, or
    • Patients who cannot tolerate CS tapering, i.e., begin CS at 2.0 mg/Kg/d, demonstrate response, but show disease progress before a 50% decrease from the initial starting dose of CS is achieved.
  • Resistance to ruxolitinib is defined as any of the following (Mohty M. 2020):
    • Progression of GvHD compared to baseline after at least 5 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement, or
    • Lack of improvement in GvHD (partial response or better) compared to baseline after at least 14 days of treatment with ruxolitinib, or
    • Loss of response, defined as objective worsening of GvHD determined by increase in stage, grade or new organ involvement at any time after initial improvement, or
    • Absence of complete response or very good partial response at day 28 after ruxolitinib.
  • Intolerance to ruxolitinib is defined as GvHD manifestations persisting without improvement in patients who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib.
  • aGVHD: acute graft-versus-host disease
  • GI:gastrointestinal
  • MAGIC: Mount Sinai Acute GVHD International Consortium
  • ORR: overall response rate
  • SR: steroid-refractory
  • D: Day
  • M: Month