Kite’s Tecartus Receives Conditional EU Approval as First CAR-T Therapy for Relapsed/Refractory Mantle Cell Lymphoma with 93% Response Rate

December 17, 2020 /BIOON/ -- Kite, a Gilead company specializing in T-cell therapy, recently announced that the European Commission (EC) has granted conditional approval for Tecartus (brexucabtagene autoleucel, formerly known as KTE-X19), a chimeric antigen receptor T-cell (CAR-T) therapy, 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 Bruton's tyrosine kinase (BTK) inhibitor. In Europe, conditional approval is initially valid for one year but may be extended or converted to unconditional approval upon submission and evaluation of additional confirmatory data.

In the United States, Tecartus received accelerated approval from the FDA in July this year for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL). In the US and the EU, Tecartus had previously been granted Breakthrough Therapy Designation (BTD) and Priority Medicines (PRIME) status, respectively.

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma (NHL) that originates from cells in the “mantle zone” of lymph nodes and typically affects men over the age of 60. MCL is highly aggressive upon relapse, with many patients experiencing progressive disease during treatment. Patients with relapsed or refractory (R/R) MCL who have received two or more prior systemic therapies, including Bruton’s tyrosine kinase (BTK) inhibitors, have a poor prognosis, with a median overall survival of only 6–10 months. In Europe, at least 7,400 new cases of MCL are diagnosed annually.

It is worth noting that,Tecartus is the first and only CAR-T therapy approved for the treatment of R/R MCL, offering patients a transformative treatment option.Data from the pivotal ZUMA-2 clinical trial show that,Tecartus achieved an overall response rate (ORR) of up to 93% and a complete response rate (CR) of 67% with a single infusion.

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

This EU approval is based on data from the registrational Phase II clinical study ZUMA-2. This was a single-arm, multicenter, open-label study conducted in adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL) whose disease had progressed or recurred after five prior lines of therapy, including anthracycline- or bendamustine-based chemotherapy regimens, anti-CD20 monoclonal antibodies, and the BTK inhibitors ibrutinib or acalabrutinib. The study aimed to evaluate the efficacy (in 60 patients) and safety (in 82 patients) of a single infusion of KTE-X19. The primary endpoint was the objective response rate (ORR), defined as the sum of the complete response (CR) and partial response (PR) rates assessed by an Independent Radiologic Review Committee (IRRC).

A total of 74 patients were enrolled in the study. Tecartus was manufactured for 71 patients, and 68 patients received a single infusion. The results showed that the overall response rate (ORR) was 93% and the complete response (CR) rate was 62% following a single infusion of Tecartus. In all patients, the follow-up duration was at least 6 months after the first objective disease response. The median duration of response (DoR) had not been reached. In this trial, 18% of patients (n=82 in the safety analysis set) experienced grade ≥3 cytokine release syndrome (CRS), and 37% experienced neurological events. The most common (≥10%) grade ≥3 adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, fever, hyponatremia, hypertension, infections with unidentified pathogens, pneumonia, hypocalcemia, and lymphopenia.

The above results indicate that a single infusion of Tecartus induced remission in most patients with relapsed/refractory mantle cell lymphoma (R/R MCL), and the severe and life-threatening toxicities observed in the study were consistent with those reported for other CAR-T cell therapies.

In recent years, despite some progress, patients with relapsed/refractory mantle cell lymphoma (R/R MCL) who no longer respond to their current treatment regimens face a severe lack of effective therapeutic options. Based on the encouraging results from the ZUMA-2 study, Tecartus will bring an innovative CAR-T cell therapy to the R/R MCL patient population.

T-cell therapy is a highly promising treatment modality, with Kite Pharma being a leader in this field. In late August 2017, Gilead Sciences acquired Kite Pharma for $12 billion, marking its entry into this sector. In October 2017, Kite’s first CAR-T cell therapy, Yescarta (axicabtagene ciloleucel, KTE-C19), received approval from the U.S. FDA, becoming the first CAR-T therapy approved worldwide for the treatment of diffuse large B-cell lymphoma (DLBCL). Yescarta was also the second CAR-T therapy to be approved for market launch, following Novartis’ Kymriah (tisagenlecleucel-T, CTL019).

Both Yescarta and Kymriah work by genetically modifying a patient’s own T cells to express chimeric antigen receptors (CARs) that target 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 then infused back into the patient, where they recognize and attack CD19-expressing tumor cells as well as other B cells.

In China, FOSUN Kite Biotechnology Co., Ltd. (FOSUN Kite) is advancing the development of FKC876 (proposed name: Yikililunse Injection). In mid-March this year, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) included the New Drug Application (NDA) for FKC876 in the priority review program. The application is for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma.

FKC876 is a CD19-targeted autologous CAR-T cell therapy product, developed by Fosun Kite through the introduction of Yescarta technology from Kite Pharma and authorized for localized production in China. Yescarta was approved by the U.S. FDA on October 18, 2017, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma. It was the first CAR-T cell therapy approved by the U.S. FDA for specific types of non-Hodgkin lymphoma. On August 27, 2018, YESCARTA became one of the first CAR-T cell therapy products approved for marketing and use in Europe, indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL).

Notably, FKC876 is the first CAR-T cell therapy product that Fosun Kite has advanced toward commercialization in China, and it is also the first CAR-T cell therapy product for which the National Medical Products Administration (NMPA) has formally accepted a marketing application to date. As a novel cancer treatment modality, FKC876 offers new hope and opportunities for patients in China with relapsed or refractory large B-cell lymphoma who have received two or more prior lines of systemic therapy. (Bioon.com)

Original Source: Kite’s Tecartus™ (KTE-X19) Granted Conditional Marketing Authorization for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma in Europe