ARES Trial of MaaT013 in GI-aGVHD Meets Primary End Point of GI-ORR

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The phase 3 ARES study (NCT04769895), which is evaluating MaaT013 in patients with acute graft-versus-host disease (aGVHD) with gastrointestinal (GI) involvement in the third-line treatment setting following treatment refractoriness to steroids or ruxolitinib (Jakafi), met its primary end point of GI-overall response rate (ORR) at day 28.¹

Patients who received MaaT013 (n = 66), a standardized, off-the-shelf, pooled-donor Microbiome Ecosystem Therapy, achieved a GI-ORR of 62%, including a complete response (CR) rate of 38% and a very good partial response (VGPR) rate of 20%. The ORR in all evaluable organs was 64%, including CR and VGPR rates of 36% and 18%, respectively. The GI-ORR at day 28 exceeded the expected response rate of 38%, and independent review committee–assessed responses exceed the per-protocol prespecified response threshold.

Moreover, the estimated 12-month overall survival (OS) rate was 54%, and the median OS was not yet reached. The estimated 12-month OS rate among responders at day 28 was 67% compared with 28% among nonresponders (P < .0001).

“GI involvement in aGVHD is a devastating condition, particularly for patients who do not respond to ruxolitinib,” Mohamad Mohty, MD, PhD, a professor of hematology and head of the Clinical Hematology and Cellular Therapy Department at Saint-Antoine Hospital and Sorbonne University in Paris, France, stated in a news release. “These individuals face an urgent unmet medical need with alarmingly low survival rates and a critical lack of effective treatment options. The results for MaaT013 in this phase 3 trial represent a groundbreaking advancement in third-line treatment for GI-aGVHD. By directly targeting the gut-immune interface, this innovative therapy has the potential to redefine disease management, bringing new hope to patients and clinicians alike.”

ARES was a single-arm study that enrolled adult patients with GI-aGVHD across 50 sites in Austria, Belgium, France, Germany, Italy, and Spain.^1,2Patients were required to undergo allogeneic hematopoietic stem cell transplantation with any type of donor, stem cell source, GVHD prophylaxis, or conditioning regimen. Patients also needed to have an aGVHD episode with GI involvement per Mount Sinai Acute GVHD International Consortium guidelines, with or without other organ involvement.² Eligible patients also needed to be resistant to steroids and resistant or intolerant to ruxolitinib or have a contra-indication to the agent.

Following enrollment, eligible patients received pretreatment therapy with oral vancomycin (Vancocin) at a dose of 250 mg 4 times daily on days 0 and 1. On day 2, patients received 1 dose of MaaT013 vial rectal enema; between days 3 to 5, patients received another dose of MaaT013, followed by 1 dose 7 +/– 2 days after the last dose during week 2 and another dose 7 +/– 2 days after the last dose during week 3. A supplementary dose of MaaT013 was permitted in case of GVHD relapse or massive antibiotic use.

Secondary end points of the study included safety and tolerability, aGVHD ORR at various time points, GI-aGVHD ORR at various time points, best response rates, survival rates, duration of response, and chronic GVHD incidence and severity.

The median age of the patients included in the data update was 55.5 years (range, 24.0-76.0), and most patients were male (53%).¹ Patients had grade II (9.1%), grade III (57.6%), or grade IV (33.3%) aGVHD. All patients were refractory to ruxolitinib, and 86.4% of patients were steroid refractory. No patients were intolerant to ruxolitinib, and 13.6% of patients were steroid dependent.

Previous safety data from ARES showed that MaaT013 was well tolerated and was not associated with increased infection risk or treatment-related fatal adverse effects in the first 30 patients who were treated.

“We would like to thank all patients who participated in this landmark study,” Gianfranco Pittari, MD, PhD, chief medical officer of MaaT Pharma, added in the news release.“These positive topline results strongly position MaaT013 as a first-in-class therapeutic for GI-aGVHD, potentially bringing a new option for patients in need of effective treatments when both steroids and ruxolitinib have failed. ARES represents the first-ever positive pivotal clinical study for an immunosuppressant-sparing, microbiome-based approach, confirming MaaT Pharma’s leadership in the field, validating the company’s therapeutic platform, supporting its programs, and broadening potential applications in oncology, inflammation, and other therapeutic areas.”

References

1. MaaT Pharma announces positive topline results from the pivotal phase 3 ARES study evaluating MaaT013 in acute graft-versus-host disease. News release. MaaT Pharma. January 8, 2025. Accessed January 9, 2025. https://www.maatpharma.com/january-8-2025-maat-pharma-announces-positive-topline-results-from-the-pivotal-phase-3-ares-study-evaluating-maat013-in-acute-graft-versus-host-disease/
2. MaaT013 as salvage therapy in ruxolitinib refractory GI-aGVHD patients (ARES). ClinicalTrials.gov. Updated October 17, 2024. Accessed January 8, 2025. https://clinicaltrials.gov/study/NCT04769895