Interim results from an ongoing Phase 1 clinical trial for an off-the-shelf CAR-T therapy indicate that no dose-limiting toxicities or severe cytokine release syndrome instances occurred in an early and limited cohort of patients.
The results were reported in Nature Communications on Nov. 24. Vanderbilt-Ingram Cancer Center accrued the most patients nationwide for the clinical trial for P-BCMA-ALLO1 – a chimeric antigen receptor T cell therapy (CAR-T) derived from healthy donors’ white blood cells. Currently, all CAR-T therapies approved by the U.S. Food and Drug Administration are autologous or made individually from each patient’s own reengineered T cells. An off-the-shelf or allogenic therapy derived from healthy donors would expedite the manufacture of this immunotherapy and make it readily available to patients, allowing them to start treatment sooner and expanding access to those patients not healthy enough for their own T cells to be reengineered.
The results reported in the Nature Communications study include data from 11 patients who received enhanced lymphodepletion, which is short-course chemotherapy to reduce the number of lymphocytes and create a favorable environment for the CAR-T therapy. Clinical analyses of patient responses and additional enrollment continue in the ongoing phase 1 trial.
“P-BCM-ALLO1 differs from other CAR T-cell products due to the non-viral vector gene editing technology used during manufacturing. This approach allows P-BCMA-ALLO1 to retain T-cell memory phenotype compared with an activated T-cell phenotype common with CAR-T products using a viral-vector,” said Bhagirathbhai Dholaria, MBBS, associate professor of Medicine at Vanderbilt University Medical Center, who is leading the clinical trial at VUMC and is one of the study’s lead authors.
P-BCMA-ALLO1 has exhibited characteristics that are crucial for CAR-T therapy because it is typically a one-and-done treatment. The study’s authors noted that the therapy had an optimal potency profile characterized by a strong memory phenotype and significant proliferative capacity. They stated that it “functions as a prodrug, conferring multipotency to rapid expansion and control of the tumor.”
The interim results do not include enough data to make determinations about clinical efficacy of P-BCMA-ALLO1 because of the limited number of participant responses analyzed at this point, but Dholaria has observed positive results in individual patients.
“I have observed remarkable response rates in heavily pre-treated multiple myeloma with minimal cytokine release syndrome or neurological side effects,” he said. “In this study, I have also treated patients who have previously failed autologous CAR-T therapies or bi-specific antibodies. The ongoing study will help determine optimal cell dose and conditioning regimen for P-BCMA ALLO1.”
The clinical trial for P-BCMA-ALLO1 is continuing to recruit participants. For more information about the clinical trial at Vanderbilt-Ingram Cancer Center, call 800-811-8480 or 615-936-5847 or email cip@vumc.org.
“These are exciting times for our patients,” said Olalekan Oluwole, MBBS, MPH, associate professor of Medicine, who leads the cellular therapy research program at Vanderbilt-Ingram. “P-BCMA-ALLO1 CAR-T was engineered for the safety of patients. Furthermore, being an off-the-shelf CAR-T product meant we could get it to our patients almost immediately.”
