Phase 2b/3 MO-TRANS Trial of Mocravimod Enrolls First Patients With AML

After the FDA cleared an investigational new drug application for mocravimod in April 2022, the first patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant have been enrolled in a phase 2b/3 study of the agent.

The first patients with acute myeloid leukemia (AML) have been enrolled in the pivotal phase 2b/3 MO-TRANS trial (NCT05429632) of mocravimod (also known as KRP203) in patients undergoing allogeneic hematopoietic cell transplant (HCT), according to a press release from Priothera.1

Mocravimod is a sphingosine 1 phosphate receptor modulator that has previously been tested for multiple autoimmune indications. The agent is currently being explored as a treatment to enhance the curative potential of allogeneic HCT, as the agent’s mechanism of action maintains graft-vs-leukemia activity while reducing tissue damage from graft-vs-host disease.

Previously, mocravimod demonstrated a clinically relevant benefit in a phase 1b/2a clinical study in patients with hematologic malignancies who are undergoing allogeneic HCT. Additionally, mocravimod received clearance from the FDA for an investigational new drug application to initiate this phase 2b/3 study.2

"We are excited to be part of the important MO-TRANS global phase 2b/3 study to investigate mocravimod, a potential new adjunctive and maintenance therapy for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant. Maintenance therapy is fast becoming the new frontier in the treatment of AML and we are committed to bringing forth new innovative therapies to AML patients," said Marcos de Lima, MD, professor of medicine at The Ohio State University College of Medicine and a hematologist/oncologist at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and principal investigator of the MO-TRANS trial, in the press release.1

The pivotal, global, phase 2b/3 MO-TRANS study is ongoing in the United States, Europe, Israel, and in additional Asian and Latin American countries. The trial aims to assess the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in patients with AML who are undergoing allogeneic HCT.3

In the double-blind, placebo-controlled study, investigators will evaluate mocravimod at 2 dose levels, 3 mg or 1 mg, in order to determine the primary end point of relapse-free survival and secondary end point of overall survival compared with placebo. Patients will continue treatment once per day for 12 months.

Enrollment in the study is open to patients 18 to 75 years of age with a diagnosis of AML and an ECOG performance status of 0 or 1. Patients must also have planned allogeneic HCT from a fully matched sibling donor or unrelated donor using a peripheral blood stem cell graft, planned use of protocol-suggested myeloablative conditioning regimen, and planned use of cyclosporine A and methotrexate or tacrolimus and methotrexate for graft-vs-host disease prophylaxis.

Patients will be excluded from the trial if they are receiving anti-thymocyte globulin, post-transplantation cyclophosphamide, sirolimus, mycophenolate mofetil, abatacept, or any other approved or non-approved medication other than cyclosporine A and methotrexate or tacrolimus and methotrexate. If patients have a diagnosis of macular edema during screening or cardiac, pulmonary, hepatic, or renal dysfunction, they will also be excluded from the study.

Topline data from this trial are expected to be announced in 2025.

"This MO-TRANS global phase 2b/3 study builds on pre-clinical and clinical proof of concept studies which demonstrated mocravimod's ability to improve survival outcomes for patients with hematological malignancies requiring allogeneic HCT. The mode of action has been well-established in autoimmune indications, but never in hematology. Mocravimod has the potential to be a first-in-class therapy in maintaining the graft-versus-leukemia effect, while preventing graft-versus-host disease, one of the most serious complications of allogeneic HCT. We expect this trial to deliver important clinical data supporting the registration of mocravimod in this indication," added Elisabeth Kueenburg, MD, chief medical officer of Priothera, in the press release.

REFERENCES:
  1. Priothera announces first patients enrolled in pivotal MO-TRANS global Phase 2b/3 study with mocravimod as an adjunctive and maintenance therapy for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplant (HCT). News release. Priothera Ltd. January 23, 2023. Accessed January 23, 2023. https://prn.to/3QXatLR
  2. Priothera receives FDA clearance of investigational new drug (IND) to start phase 2b/3 study with mocravimod in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). News release. Priothera Ltd. April 25, 2022. Accessed January 23, 2023. https://prn.to/3Xu5ftf
  3. Phase IIb placebo-controlled study of mocravimod as adjunctive and maintenance treatment in AML patients in allo-hsct (MO-TRANS). ClinicalTrials.gov. Updated January 20, 2023. Accessed January 23, 2023. https://clinicaltrials.gov/ct2/show/NCT05429632