First Patient With AML Receives CD33-CAR T Cells From Previous HCT Donor


Vor Bio recently also announced data from the phase 1/2 trial of trem-cel.

Guenther Koehne, MD, PhD

Guenther Koehne, MD, PhD

Credit Miami Cancer Institute

Vor Bio has dosed the first patient with previously transplanted acute myeloid leukemia (AML) in the phase 1/2 VBP301 trial (NCT05984199) of VCAR33ALLO CD33-directed chimeric antigen receptor (CAR)-T cell therapy.1

“We are pleased to start 2024 with strong execution and we look forward to sharing initial clinical data from the VBP301 trial later this year,” Eyal Attar, MD, Vor Bio, Chief Medical Officer, said in a statement.1 “We are excited to bring to AML patients, for the first time, a healthy transplant donor-derived CAR-T developmental therapy which may overcome shortfalls seen with either autologous or allogeneic off-the-shelf approaches.”

VCAR33ALLO is made from healthy lymphocytes obtained from the same donor from which the patient was previously transplanted, which Vor believes has greater potential for expansion, persistence, and anti-leukemia activity compared to an autologous product. The update also represents the successful manufacturing of VCAR33ALLO in the company’s in-house manufacturing facility.

The first patient treated in the multicenter, open-label, first-in-human study had their disease relapse after standard-of-care treatment, but the trial is also enrolling patients whose disease has relapsed after receiving tremtelectogene empogeditemcel (trem-cel; VOR33), Vor’s genome-edited, CD33-deleted, hematopoietic stem cell transplant therapy. The company is interested in investigating the combination trem-cel +VCAR33 treatment system to reduce the risk of relapse or treat evidence of relapse.Initial data from the trial is expected in the second half of 2024.

READ MORE: Hemogenyx Sends the FDA a Complete Response Related to the IND Hold on AML CAR-T HEMO-CAR-T

Vor recently presented data on the phase 1/2a clinical trial (NCT04849910) of trem-cel in combination with gemtuzumab ozogamicin (Mylotarg) at the ASTCT/EBMT 6th International Conference on Relapse After Transplant and Cellular Therapy (HSCT²) in Los Angeles, California in November 2023.2

“With this additional hematologic protection data in multiple patients over multiple doses of Mylotarg, we are now seeing the promise of our approach come to light as a potential next-generation therapeutic option for AML patients,” Attar said in a statement at that time.2 “Now with VCAR33ALLO in the clinic, we have the potential for an even better combination with trem-cel with the goal of providing durable responses or even a potential cure for AML.”

Investigators observed primary neutrophil engraftment occurred in all 7 patients treated at a median of 10 days with a median platelet recovery at 15.5 days, excluding 1 patient with previously documented anti-platelet antibodies (immune thrombocytopenia). All 3 patients treated with Mylotarg experienced hematologic protection from deep cytopenias through repeat doses and pharmacokinetics in these patients revealed that the 0.5 mg/m2 dose was within the exposure range measured for the therapeutic dose of Mylotarg in this population. The percentage of CD33-negative donor cells also increased following Mylotarg administration.2

Vor now plans to initiate dose escalation of Mylotarg to 1.0 mg/m2 as well as provide treatment opportunities for patients who become measurable residual disease positive or relapse, such as induction-course Mylotarg and VCAR33ALLO.

“The results being presented further validate Vor Bio’s platform and approach. We are excited to see that trem-cel has worked as expected in these patients, providing them with hematologic protection and exposing their leukemia to targeted therapy,” the presenter, investigator Guenther Koehne, MD, PhD, Deputy Director and Chief, Blood & Marrow Transplant and Hematologic Oncology, Miami Cancer Institute, Baptist Health South Florida, added.2

1. Vor Bio doses first AML patient with VCAR33 (ALLO) and provides corporate update. News release. Vor Bio. January 17, 2024.
2. Vor Bio presents positive data update on Trem-cel at HSCT² conference. News release.
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