Talicabtagene autoleucel for patients with R/R B-cell malignancies: Results from a phase I/II trial

Outcomes for patients with R/R B-cell malignancies in low- and middle-income countries remain poor compared with the rest of the world, with a lack of effective therapies contributing to this disparity.¹ Talicabtagene autoleucel (formerly actalycabtagene autoleucel) is a novel, humanized, second-generation, anti-CD19 4-1BB CAR T-cell therapy developed to address these challenges.¹

An open-label, multicenter, phase I/II trial assessed the efficacy and safety of talicabtagene autoleucel in patients aged ≥15 years with R/R B-cell ALL (n = 17) or B-cell lymphoma (n = 47) across six centers in India.¹ Results from this trial were published in Lancet Haematology by Jain et al.¹

Key learnings 

In the phase I part (n = 14), no DLTs were observed at doses of 2 × 10⁶ – 17 × 10⁶ CAR T-cells per kg. A dose of ≥5 × 10⁶ CAR T-cells per kg was selected as the phase II dose as a result of a CR in 3 out of 7 patients.

The phase II primary endpoint was met; the ORR was 73% in the efficacy-evaluable population (B-cell lymphoma, n = 36; B-cell ALL, n = 15), with the median DOR not reached.

The most common Grade ≥3 AEs were hematological events, including neutropenia (96%), thrombocytopenia (65%), anemia (61%), and febrile neutropenia (47%). Two treatment-related deaths occurred.

Talicabtagene autoleucel demonstrated a manageable safety profile and durable responses in patients with B-cell malignancies, with local manufacturing and a short vein-to-vein time (median 18 days) enabling timely delivery and allowing the potential for this therapy to be viable in low-resource settings.