Investigational Microbiotherapy MaaT033 Is Safe in Allo-HSCT Recipients

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MaaT033 has been deemed tolerable and has a favorable safety profile in patients with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) in the ongoing phase 2b PHOEBUS trial (NCT05762211), according to findings from an unblinded interim safety review from an independent data safety monitoring board (DSMB).1

MaaT033 is a standardized, pooled multi-donor–derived, freeze-dried oral microbiotherapy. Based on these findings, the DSMB has recommended the PHOEBUS trial to continue without modification.

“We are pleased to report that MaaT033’s safety profile continues to be positive,” Gianfranco Pittari, MD, PhD, chief medical officer of MaaT Pharma, the developer of MaaT033, stated in a news release. “The confirmed absence of a prespecified mortality excess in patients receiving MaaT033 is of critical relevance. These patients would enormously benefit from innovative therapies enhancing HSCT outcomes while avoiding toxic effects.”

The international, multicenter, randomized, double-blind PHOEBUS is investigating the efficacy and safety of MaaT033 vs placebo in patients undergoing allo-HSCT. Following allo-HSCT, patients are at an increased risk of non-relapse mortality (NRM). Therefore, the PHOEBUS protocol included a specific safety analysis that was designed to trigger a stopping rule in the event of a predefined mortality excess in the MaaT033 arm after 30 patients had been randomly assigned to receive the investigational agent and had been monitored for 90 days following allo-HSCT.

This safety analysis is separate from the ongoing safety assessments that are being conducted every 6 months. Positive outcomes from the second DSMB safety assessment in the ongoing safety assessment protocol were reported in January 2025 and showed that MaaT033 was well tolerated and had an acceptable safety profile among 59 evaluable patients.2

PHOEBUS is enrolling patients at least 50 years of age with hematologic malignancies for which allo-HSCT is indicated with the use of a reduced-toxicity or reduced-intensity conditioning regimen.3 Patients also need to have polynuclear neutrophil counts higher than 0.5 G/L; have received wide-spectrum antibiotics within 90 days prior to enrollment; have a Karnofsky index of at least 70%; and have an available sibling donor, unrelated stem cell donor, or familial haploidentical donor.

Patients will be excluded if they are planned to receive a non-myeloablative conditioning regimen, a conventional myeloablative conditioning regimen, a conditioning regimen with alemtuzumab, allogeneic hematopoietic cell transplantation (allo-HCT) with cord blood cells, allo-HCT from an unrelated donor with at least 3 out of 10 HLA mismatches; are receiving a manipulated graft; are receiving a large-spectrum antibiotic at the time of randomization; are planned to receive vedolizumab (Entyvio) or abatacept (Orencia) for graft-vs-host disease (GVHD) prophylaxis; have creatinine clearance levels lower than 30 mL per minute; have bilirubin or aminotransferase abnormalities contraindicating allo-HCT; have a cardiac ejection fraction of less than 40%; or have pulmonary impairment with less than 50% lung carbon monoxide diffusing capacity.

Patients receive 3 oral capsules per day of either MaaT033 or placebo. The primary end point is OS with MaaT033 12 months after allo-HCT. Secondary end points include restoration of gut microbiota diversity, grade 2 to 4 acute GVHD (aGVHD), grade 3/4 aGVHD, NRM, infectious-related mortality, GVHD-related mortality, GVHD-free relapse-free survival, quality of life, severe infections, rate of immune suppression therapy discontinuation, time to platelet engraftment, time to neutrophil engraftment, and the incidence of adverse effects.

Enrollment to PHOEBUS is ongoing in Belgium, France, Germany, Netherlands, Spain, and the United Kingdom. The trial plans to enroll 387 patients and will be conducted at up to 60 investigational sites.

The next DSMB unblinded interim analysis that will include mortality monitoring is scheduled to be conducted in the third quarter of 2025 at the 120-patient mark. The next routine DSMB ongoing safety review readout is also expected in the third quarter of 2025.

References

1. April 8, 2025: MaaT Pharma announces positive safety interim analysis from DSMB for phase 2b trial evaluating MaaT033 for patients receiving allo-HSCT. News release. MaaT Pharma. April 8, 2025. Accessed April 9, 2025. https://www.maatpharma.com/april-8-2025-maat-pharma-positive-safety-interim-analysis-phase-2b-trial-evaluating-maat033-in-allo-hsct/
2. January 21, 2025: MaaT Pharma announces positive second DSMB review of ongoing phase 2b clinical trial evaluating MaaT033 for patients receiving allo-HSCT. News release. MaaT Pharma. January 21, 2025. Accessed April 9, 2025.https://www.maatpharma.com/january-21-2025-maat-pharma-announces-positive-second-dsmb-review-of-ongoing-phase-2b-clinical-trial-evaluating-maat033-for-patients-receiving-allo-hsct/
3. Oral pooled fecal microbiotherapy to prevent allogeneic hematopoietic cell transplantation complications (PHOEBUS trial). ClinicalTrials.gov. Updated December 27, 2024. Accessed April 9, 2025. https://clinicaltrials.gov/study/NCT05762211