The U.S. Food and Drug Administration ( FDA ) has granted accelerated approval to Tecartus ( Brexucabtagene autoleucel, formerly KTE-X19 ), the first and only approved chimeric antigen receptor ( CAR ) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma ( MCL).
Tecartus is an autologous, anti-CD19 CAR T cell therapy.
The approval of this one-time therapy follows a priority review and FDA Breakthrough Therapy Designation and is based on results of ZUMA-2, a single-arm, open-label study in which 87% of patients responded to a single infusion of Tecartus, including 62% of patients achieving a complete response ( CR ).
Among patients evaluable for safety, 18% experienced grade 3 or higher cytokine release syndrome ( CRS ) and 37% experienced grade 3 or higher neurologic toxicities.
Tecartus has a Boxed Warning in its product label regarding the risks of cytokine release syndrome and neurologic toxicities.
A Risk Evaluation and Mitigation Strategy ( REMS ) has been approved by the FDA for Tecartus and has been combined with the Yescarta ( Axicabtagene ciloleucel ) REMS. The REMS program will inform and educate healthcare professionals about the risks associated with Tecartus therapy, and training and certification on the REMS program will be an integral part of the final authorization for centers offering Tecartus.
Tecartus will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California. In the ZUMA-2 trial, Kite demonstrated a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Manufacturing speed is especially critical for patients with advanced disease, who are very ill and at risk for quick progression.
The ZUMA-2 trial enrolled 74 adult patients with relapsed or refractory mantle cell lymphoma who had previously received anthracycline- or Bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor ( Ibrutinib or Acalabrutinib ).
The primary endpoint was objective response rate ( ORR ) per the Lugano Classification ( 2014 ), defined as the combined rate of complete responses and partial responses as assessed by an Independent Radiologic Review Committee ( IRRC ).
In the study, 87% of patients ( n=60 evaluable for efficacy analysis ) responded to a single infusion of Tecartus, including 62% of patients who achieved a complete response.
Among all patients, follow-up was at least six months after their first objective disease response.
Median duration of response has not yet been reached.
In the trial, 18% of patients ( n=82 evaluable for safety ) experienced grade 3 or higher CRS and 37% experienced neurologic events.
The most common ( 10% or more ) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia and lymphopenia.
Mantle cell lymphoma is a rare form of non-Hodgkin lymphoma ( NHL ) that arises from cells originating in the mantle zone of the lymph node and predominantly affects men over the age of 60.
Mantle cell lymphoma is highly aggressive following relapse, with many patients progressing following therapy. ( Xagena )
Source: Gilead, 2020