Jūlijs 25, 2021: Kite, Gilead Company (Nasdaq: GILD), šodien paziņoja, ka FDA ir piešķīrusi pirmo un vienīgo apstiprināto TecartusTM (brexucabtagene autoleucel, agrāk KTE-X19) himēriskā antigēna receptoru CAR T-šūnu terapija for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, accelerated approval (MCL). The FDA granted priority review and breakthrough therapy designation to this one-time therapy, which was based on the results of ZUMA-2, a single-arm, open-label study in which 87 percent of patients responded to a single infusion of Tecartus, with 62 percent achieving a complete response (CR). 18% of patients who were evaluated for safety had citokīnu atbrīvošanas sindroms (CRS) of Grade 3 or higher, and 37% had neurologic toxicities of Grade 3 or higher.
“Despite promising advances, there are still significant gaps in treatment for MCL patients who progress after initial therapy,” said Michael Wang, MD, ZUMA-2 Lead Investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center. “Many patients have high-risk disease, which means they are more likely to progress despite treatment. “Tecartus is the first cell therapy available to people with relapsed or refractory MCL. It has an impressive response rate of nearly 90% and early clinical evidence suggests that remissions may last through later lines of therapy. This makes it an important choice for these patients.”
“Mēs esam lepni uzsākt savu otro šūnu terapiju, jo Kite ir apņēmusies dot solījumu CAR T terapija to patients with haematological cancers,” said Christi Shaw, Kite’s Chief Executive Officer. “I would like to express my gratitude to the patient study participants, caregivers, clinical researchers, regulators, and dedicated Kite colleagues who contributed to this approval, and we look forward to working with the limfoma community to bring this potentially transformative therapy to patients with relapsed or refractory MCL.”
Tecartus’ product label includes a boxed warning about the risks of DRS and neurologic toxicities. The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Tecartus, which has been combined with the REMS for Yescarta® (axicabtagene ciloleucel). The REMS programme will inform and educate healthcare professionals about the risks associated with Tecartus therapy, and training and certification in the REMS programme will be a requirement for centres offering Tecartus therapy to receive final authorization.
MCL is a rare type of ne-Hodžkina limfoma (NHL) that develops from cells in the lymph node’s “mantle zone” and primarily affects men over the age of 60. Following a relapse, MCL is extremely aggressive, and many patients progress after treatment.
The Lymphoma Research Foundation’s Chief Executive Officer, Meghan Gutierrez, said, “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.” “Researchers have made significant progress in our understanding of this disease over the last decade, and we’ve seen an increase in patient clinical trials, which we hope will continue to improve treatment strategies and options for people with mantle cell lymphoma. Today’s news builds on that progress and gives mantle cell patients and their families reason to be hopeful.”
Kite’s commercial manufacturing facility in El Segundo, California, will produce Tecartus. Kite achieved a 96 percent manufacturing success rate in the ZUMA-2 trial, with a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Patients with advanced disease, who are severely ill and at risk of rapid progression, require manufacturing speed in particular.
Kite Konnect®, integrēta tehnoloģiju platforma, kas sniedz informāciju un palīdzību visā terapijas procesā Kite komercializētajam CAR T terapijas, including courier tracking for shipments and manufacturing status updates, is available to patients whose healthcare professionals have prescribed Tecartus therapy. Kite Konnect is a support system for patients who are receiving Yescarta or Tecartus, as well as information for the healthcare teams who are supporting them.
KTE-X19 pašlaik tiek vērtēts Eiropas Savienībā, un Eiropas Zāļu aģentūra ir piešķīrusi tai prioritāro zāļu (PRIME) apzīmējumu recidivējošai vai ugunsizturīgai MCL.
Tecartus izmēģinājuma rezultāti
The approval of Tecartus is based on results from the ongoing ZUMA-2 pivotal trial, which is a single arm, open-label study. 74 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, anti-CD20 antibody treatment, or a Bruton tyrosine kinase inhibitor were enrolled in the trial (ibrutinib or acalabrutinib). The primary endpoint was the objective response rate (ORR), which was defined as the combined rate of CR and partial responses as judged by an Independent Radiologic Review Committee according to the Lugano Classification (2014). (IRRC).
Pētījumā 87 procenti pacientu (n = 60 novērtējami efektivitātes analīzei) reaģēja uz vienu Tecartus infūziju, un 62 procenti sasniedza pilnīgu atbildes reakciju. Pēcpārbaude visiem pacientiem bija vismaz sešus mēnešus pēc pirmās objektīvās atbildes reakcijas uz slimību. Vidējais reakcijas laiks vēl nav noteikts.
In the experiment, 18% of patients (n=82 evaluable for safety) had Grade 3 or higher CRS, while 37% of patients had neurologic problems. Anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unclear, pneumonia, hypocalcemia, and lymphopenia were the most prevalent Grade 3 or higher adverse effects (10%). With a Risk Evaluation and Mitigation Strategy, the FDA approved Tecartus (REMS). The Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program has been integrated with the Tecartus REMS and is now known as the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program”
Par Tecartus
Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP™ manufacturing process that includes T cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature. In addition to MCL, Tecartus is also currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL) and hroniska limfoleikoze (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.
Tecartus indikācija
Tecartus ir uz CD19 vērsta ģenētiski modificēta autologa T šūnu imūnterapija, kas paredzēta pieaugušiem pacientiem ar recidivējošu vai refraktāru mantijas šūnu limfomu (MCL).
Šī indikācija ir apstiprināta ar paātrinātu apstiprinājumu, pamatojoties uz vispārējo reakcijas ātrumu un reakcijas ilgumu. Šīs indikācijas turpmāka apstiprināšana var būt atkarīga no klīniskā ieguvuma pārbaudes un apraksta apstiprinošā pētījumā.
