On July 24, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to brexucabtagene autoleucel (Tecartus™), a CD19-directed genetically modified autologous T cell immunotherapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
Approval was based on an open-label, multicenter, single-arm trial (ZUMA-2; NCT02601313) of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. Patients received a single IV infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate (ORR) per Lugano 2014 criteria as assessed by an independent review committee (IRC).
Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of six months, ORR was 87% (95% CI = 75, 94) with a complete remission (CR) rate of 62% (95% CI = 48, 74). The estimated median duration of response was not reached (0–29.2+ months) after a median follow-up of 8.6 months for duration of response. Of all 74 patients with leukapheresis, ORR as assessed by IRC was 80% (95% CI = 69, 88) with a CR rate of 55% (95% CI = 43, 67).
The most common grade 3 or higher reactions (≥ 10%) were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection (pathogen unspecified), pneumonia, hypocalcemia, and lymphopenia.
FDA approved brexucabtagene autoleucel with a risk evaluation and mitigation strategy because of the risk of cytokine release syndrome and neurologic toxicities.
The recommended dose of brexucabtagene autoleucel is a single IV infusion of 2 x 106 CAR-positive viable T cells per kg body weight (maximum 2 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.
FDA approved the indication under accelerated approval based on ORR and durability of response. Continued approval for the indication may be contingent on verification and description of clinical benefit in a confirmatory trial.
FDA granted orphan drug designation, breakthrough therapy designation, and priority review to brexucabtagene autoleucel for the indication. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.