The VBP101 trial is actively recruiting and we anticipate initial clinical data in Q4 of 2022. If successful, this trial will provide important validating evidence of the potential of VOR33 and our broader engineered Hematopoietic Stem Cell (eHSC) approach. We plan to initially evaluate engraftment and tolerability, then preliminarily assess clinical activity in the second part of the trial.
The primary goals of the VBP101 trial are to evaluate tolerability and feasibility, with a focus on confirming that VOR33 can engraft in patients in a timely manner. Patients will then be eligible for subsequent treatment with Mylotarg. We will examine the incidence of hematopoietic toxicities associated with Mylotarg in patients engrafted with VOR33. Any observed protection from such on-target toxicity in this Phase 1/2a trial would serve as an important proof of principle for our research and development platform. While this trial is not powered to confirm significance of efficacy, relapse-free survival and overall survival will be assessed.
Enrollment & follow-up
The VBP101 trial (NCT04849910) is open to AML patients who are at high risk of relapse and undergoing myeloablative hematopoietic stem cell transplant (HCT). Participants (18-70 years old) must have a diagnosis of CD33+ AML, an HLA-matched related or unrelated (10/10) donor and be a candidate for myeloablative HCT. Additional key inclusion criteria include morphologic remission with intermediate/poor cytogenetics and the presence of minimal residual disease. Patients with 5-10% bone marrow-only blasts with any cytogenetic risk are also eligible. Key exclusion criteria include prior auto/allo-HCT or treatment with Mylotarg.
To administer VOR33, HSCs from matched healthy donors will be mobilized and isolated from peripheral blood, engineered into VOR33 and then introduced into patients following myeloablative conditioning. As a safety measure, we will freeze and preserve a portion of the original donor cells to use in case of the failure of VOR33 to engraft.
At day 60, we will re-evaluate patients for disease status and peripheral blood counts. Those patients remaining in remission and meeting dosing criteria will be treated with maintenance doses (escalated in separate dosing cohorts) of Mylotarg once a month for four months to potentially reduce the risk of relapse by killing residual AML cells. Patients in early relapse may be treated with salvage therapies including Mylotarg. Patients will be followed up for two years after HCT and for up to 15 years post-HCT in a separate long-term follow-up study.