On July 24, Gilead subsidiary Kite announced that the FDA had granted accelerated approval for Tecartus (brexucabtagene autoleucel, KTE-X19) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
Mantle Cell Lymphoma (MCL) is one of more than 70 subtypes of non-Hodgkin lymphoma (NHL), accounting for 6%–7% of NHL cases. According to authoritative data from CA: A Cancer Journal for Clinicians, there were over 500,000 new cases of NHL globally in 2018, making MCL a relatively common subtype in terms of patient numbers. As the median age at onset for MCL is over 60 years, and most patients are already at stage III or IV at diagnosis, many are unsuitable for, unwilling to undergo, or even abandon treatments such as systemic radiotherapy and stem cell transplantation. If MCL relapses after initial therapy, the disease is highly aggressive and tends to progress rapidly.
Tecartus (KTE-X19) is a CD19 CAR-T therapy developed by Gilead/Kite using a novel manufacturing process. It shares the same CAR structure as Yescarta (KTE-C19), which was previously approved for market launch; however, during the manufacturing process, KTE-X19 filters out CD19+ tumor cells to reduce premature activation and exhaustion of CAR-T cells, thereby improving manufacturing success rates. Tecartus is manufactured at Kite Pharma’s facility in El Segundo, California. In the ZUMA-2 study, the manufacturing success rate reached 96%, with a median manufacturing time for CAR-T cells (from leukapheresis to infusion) of 15 days. For critically ill patients with advanced-stage disease at high risk of rapid progression, the speed of CAR-T cell manufacturing is crucial.
Based on the results of the ZUMA-2 study, Tecartus was granted Breakthrough Therapy Designation and Priority Review by the FDA for the treatment of MCL, and it is currently the first and only approved CAR-T therapy for MCL. Tecartus also received the Priority Medicines (PRIME) designation from the EMA for the treatment of relapsed or refractory MCL and is currently under review.
The pivotal Phase II ZUMA-2 study is currently ongoing. This single-arm, open-label trial enrolled a total of 74 adult patients with relapsed or refractory mantle cell lymphoma (MCL) who had previously received anthracycline- or bendamustine-containing chemotherapy regimens, anti-CD20 antibody therapy, and a Bruton’s tyrosine kinase (BTK) inhibitor (ibrutinib or acalabrutinib). The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).
The results showed that after a single infusion of Tecartus, 60 patients had evaluable efficacy, with an overall response rate of 87%, including a complete response rate of 62%. All responding patients were followed for more than 6 months, and the median duration of response data is not yet mature.
Among the 82 patients with evaluable safety data, the incidence of grade ≥3 cytokine release syndrome (CRS) was 18%, and the incidence of grade ≥3 neurotoxicity was 37%. The most common (≥10%) grade ≥3 adverse reactions included anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, fever, hyponatremia, hypertension, infection with unidentified pathogen, pneumonia, hypocalcemia, and lymphopenia. The FDA also approved a Risk Evaluation and Mitigation Strategy (REMS) for Tecartus and included a boxed warning in its drug labeling to highlight the risks of CRS and neurotoxicity.
In addition to MCL, Phase I/II clinical studies of Tecartus for the treatment of acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are also ongoing.