First-in-Human Phase I Study Results Presented: Trispecific CAR T-Cell Therapy

A first-in-human phase I study has evaluated trispecific chimeric antigen receptor (CAR) T-cell therapy for targeting CD19, CD20, or CD22. This therapy is safe and viable for production, according to findings presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

“Despite lack of persistence of cells beyond day 30, durable remissions have been observed. Remissions have been observed in [mantle cell lymphoma (MCL)], [follicular lymphoma (FL)], [diffuse large B-cell lymphoma (DLBCL)] and [B-cell acute lymphoblastic leukemia (B-ALL)],” explained lead author Evandro Bezerra, MD, of the Ohio State University, Columbus.

For the study, successful manufacture of a trispecific CAR T-cell product was achieved for 15 of 16 patients, with a median transduction efficiency of 26%, median fold expansion of 5, and median time to manufacturing of seven days.

Among 15 patients, complete response (CR) was achieved in six, two of whom by day 30 and four by day 90.

Of nine patients with non-Hodgkin lymphoma (NHL), five achieved CR, three of whom have maintained CR beyond one year following treatment.

CR was observed in patients with B-ALL, DLBCL, FL, and MCL, while there were no responses in patients with Richter’s transformation. One patient with B-ALL had achieved response after disease progression following commercial anti-CD19 CAR T-cell therapy. In patients with chronic lymphocytic leukemia (CLL) and B-cell prolymphocytic leukemia (B-PLL) stable disease was observed at day 30.

In three patients who had disease relapse, biopsy was performed to evaluate CD19, CD20, or CD22 expression before and after the trispecific CAR T-cell therapy.

“In one patient, CD20 positivity changed to CD20 dim expression upon relapse. In another patient, CD20 negative status changed to CD20 + after CAR-T,” Dr. Bezerra noted.

Regarding safety events, cytokine release syndrome (CRS) occurred in three patients, two experiencing grade 1, one experienced grade 2, and all required tocilizumab. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). There were no occurrences of hemophagocytic lymphohistiocytosis observed and no patients required steroids.

Among the patients who achieved CR, pleomorphic sarcoma manifested in one and prostate cancer in another, both malignancies deemed unrelated to the treatment. Mortality due to intracranial hemorrhage occurred on day 32 in one patient with persistent B-ALL.

Reference

Vasu S, Bezerra E, Denlinger N, et al. Initial results of a first-in-human, phase I study point-of-care manufacturing of trispecific CAR-T cells targeting CD19/20/22 in B-cell malignancies. Abstract #2078. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.