Tecartus: First Global CAR-T Therapy for Acute Lymphoblastic Leukemia with 71% Complete Remission Rate After Single Infusion

Acute Lymphoblastic Leukemia-ALL (Image source: wikidoc.org)

June 06, 2021 /BioonBIOON/ -- Kite, a T-cell therapy company under Gilead Sciences, recently announced the primary analysis results of the ZUMA-3 trial, a global, multicenter, single-arm, open-label Phase 1/2 study evaluating Tecartus (brexucabtagene autoleucel, formerly known as KTE-X19) for the treatment of relapsed or refractory B-cell precursor acute lymphoblasticLeukemia(ALL) adult patients. Results showed that following a single infusion of Tecartus,71% of patients achieved a complete response, of whom 97% were minimal residual disease (MRD) negative.

Tecartus is a CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy., the Biologics License Application (BLA) for the treatment of adult patients with relapsed or refractory B-cell precursor ALL has been approved by the U.S.FDAAccepted and granted priority review, with a Prescription Drug User Fee Act (PDUFA) target action date of October 1, 2021.

If approved, Tecartus will become the first and only CAR-T cell therapy approved for the treatment of adult patients (≥18 years) with relapsed or refractory ALL. In 2016,FDABreakthrough Therapy Designation (BTD) was granted to Tecartus for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

In the pivotal Phase 2 portion of this study, 71 patients with relapsed or refractory disease were enrolled. Among treated patients (n=55), 47% had received three or more prior lines of therapy. With a median follow-up of 16.4 months,Following a single infusion of Tecartus, 71% of patients achieved complete response (CR) or complete response with incomplete hematologic recovery (CRi)., 31% of patients maintained response at the time of data cutoff.97% of responding patients achieved deep molecular remission with undetectable minimal residual disease (MRD)., the median overall survival (OS) for all responding patients has not been reached. Among 25 patients treated with Blincyto (blinatumomab, a CD19/CD3 bispecific BiTE immunotherapy developed by Amgen), the CR/CRi rate was 60%. Among all treated patients, the median duration of response (DOR), relapse-free survival (RFS), and OS were 12.8 months, 11.6 months, and 18.2 months, respectively.

Regarding safety, grade ≥3 adverse events occurred in 95% of patients, with the most common beingAnemia(49%) and fever (36%). Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 24% and 25% of patients, respectively, and were reversible with treatment. In the study, 2 Grade 5 treatment-related adverse events occurred (1 case of brain herniation and 1 case of septic shock).

Dr. Frank Neumann, Global Head of Clinical Development at Kite, stated: "The data presented today at ASCO confirm the response rates observed in the Phase 1 portion of the ZUMA-3 study, as well as the transformative potential of Tecartus in adult patients with ALL. Tecartus has already begun to change the treatment landscape for many patients with relapsed or refractory mantle cell lymphoma (MCL), and these new data represent a very important next step in our ongoing commitment to developing innovative therapies for patients with leukemia and lymphoma."

T-cell therapy is a highly promising treatment modality, and Kite Pharma is a leading company in this field. In late August 2017, Gilead Sciences acquired Kite for $12 billion to enter the sector. In October 2017, Kite's first CAR-T cell therapy, Yescarta (axicabtagene ciloleucel, KTE-C19), received U.S.FDAapproved, becoming the world's first CAR-T therapy approved for the treatment of DLBCL, and this therapy is also followingNovartisThe second CAR-T therapy approved for marketing after Kymriah (tisagenlecleucel-T, CTL019).

In July 2020, Tecartus received U.S.FDAAccelerated approval for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL) who have previously received two or more systemic therapies, including a BTK inhibitor. Tecartus is the first and only CAR T-cell therapy approved for the treatment of R/R MCL, offering a transformative treatment option for patients. From the pivotal ZUMA-2Clinical TrialsData show that the overall response rate (ORR) for a single infusion of Tecartus was as high as 93%, and the complete response rate (CR) was 67%. Notably, in the ZUMA-2 trial,Kite demonstrated a manufacturing success rate of up to 96% and an average manufacturing turnaround time of 15 days from leukapheresis to product delivery.Manufacturing speed is particularly critical for patients with advanced-stage disease, whose conditions are severe and carry a risk of rapid deterioration.

The mechanism of action of Yescarta, Kymriah, and Tecartus involves genetically modifying the patient's own T cells to express chimeric antigen receptors (CARs) targeting the CD19 antigen. CD19 is an antigenic protein expressed on the surface of various hematologic tumor cells, including B-cell lymphoma and leukemia cells. The engineered T cells are subsequently reinfused into the patient, thereby recognizing and attacking CD19-expressing...TumorCells and other B cells.

Tecartus is an autologous, anti-CD19 CAR-T cell therapy that utilizes the XLP manufacturing process, including T-cell selection and lymphocyte enrichment. For certain B-cell malignancies with evidence of circulating lymphoblastsTumor, lymphocyte enrichment is a necessary step. Currently, Tecartus is being developed for the treatment of mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and other indications.

Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system, and other organs. The survival rate for adult patients with relapsed or refractory ALL remains very low, with a median overall survival of approximately 8 months when treated with the most commonly used therapies. B-cell precursor ALL is the most common subtype, accounting for approximately 75% of ALL cases. Compared with other types of ALL, treatment outcomes for this subtype are generally poorer. (Bioon.com)

Original Source: Kite's Tecartus® Demonstrates High Response Rate in Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia Earning Priority Review Designation