Yescarta (Axicabtagene Ciloleucel) Demonstrates 80% Complete Response Rate in Relapsed or Refractory Indolent Non-Hodgkin Lymphoma in ZUMA-5 Trial

Gilead’s cell therapy subsidiary, Kite Pharma, recently announced the interim analysis results of the Phase II ZUMA-5 study of its CD19 CAR-T cell therapy, Yescarta (axicabtagene ciloleucel). The study was conducted in adult patients with relapsed or refractory indolent (slow-growing) non-Hodgkin lymphoma (iNHL) who had previously received at least two prior therapies. The data showed that 93% of patients achieved an objective response, and 80% achieved a complete response (CR), following a single infusion of Yescarta. These data were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

Following the release of the primary analysis results at 12 months, Kite Pharma plans to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) later this year to expand the indications for Yescarta. Yescarta was previously granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL)—two types of indolent non-Hodgkin lymphoma (NHL)—in patients who have received at least two prior lines of therapy. If approved, Yescarta would become the first and only CAR-T cell therapy approved for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma (indolent NHL, iNHL).

ZUMA-5 (NCT03105336) is a single-arm, multicenter, open-label Phase II study designed to enroll 160 adult patients (≥18 years of age) with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), including follicular lymphoma (FL) or marginal zone lymphoma (MZL) subtypes, who have previously received at least two prior systemic therapies, including a combination of an anti-CD20 monoclonal antibody and an alkylating agent. The study aims to evaluate the efficacy and safety of a single infusion of Yescarta in this patient population. The primary endpoint is the objective response rate (ORR) assessed by an Independent Review Committee (IRC) according to the Lugano classification (2014). Secondary endpoints include complete response rate (CR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, CAR T-cell kinetics, and cytokine levels. This study is ongoing.

The interim analysis showed that among patients evaluable for efficacy (n=96), the ORR was 93% and the CR rate was 80%. Subgroup analysis revealed that in patients with relapsed or refractory FL (n=80), the ORR was 95% and the CR rate was 81%, with 68% of patients still in remission after at least 9 months of follow-up. In patients with relapsed or refractory MZL (n=16), the ORR was 81%, and the CR rate was 75% after at least 1 month of follow-up. Regarding secondary endpoints, the median follow-up time for all patients was 15.3 months, the median DOR was 20.8 months, the median PFS was 23.5 months, and the median OS had not yet been reached.

In the safety analysis of 140 patients with follicular lymphoma (FL) or marginal zone lymphoma (MZL) who received treatment, grade 3 or higher cytokine release syndrome (CRS) and neurological events occurred in 8% and 17% of patients, respectively. Two grade 5 adverse events were reported in patients with FL, including one case of multi-organ failure due to CRS related to Yescarta treatment and one case of aortic dissection unrelated to Yescarta treatment. The primary analysis at 12 months of follow-up is still ongoing.

Dr. Caron A. Jacobson, Assistant Professor of Medicine at Harvard Medical School and Medical Director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute, stated: “For patients with certain indolent non-Hodgkin lymphomas (such as follicular lymphoma), despite the availability of treatment options, relapses become increasingly frequent over time, and the disease can progress to a more aggressive form. Therefore, the robust overall response rate and complete response rate data demonstrating the potential of Yescarta, announced this time, are highly promising for these patients.”

Ken Takeshita, M.D., Global Head of Clinical Development at Kite Pharma, stated, “Yescarta is significantly improving outcomes for certain patients with relapsed and refractory cancers, such as diffuse large B-cell lymphoma. These results from the ZUMA-5 study support our assessment that Yescarta has the potential to provide therapeutic benefit in indolent NHL, and we look forward to sharing the primary analysis results for patients with relapsed or refractory disease later this year.”

Yescarta was approved by the U.S. FDA in October 2017 as the first CAR-T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma (LBCL). Its specific indications include the treatment of adult patients with relapsed or refractory LBCL who have received two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBL), and DLBCL arising from follicular lymphoma (FL) (i.e., transformed FL, TFL). Yescarta is not indicated for the treatment of primary central nervous system lymphoma.

In China, Yescarta (axicabtagene ciloleucel injection [proposed], code FKC876) is being developed by Fosun Kite Biotechnology Co., Ltd. (FOSUN Kite), a joint venture established by Shanghai Fosun Pharmaceutical Group and Kite Pharma. In mid-March this year, Fosun Kite announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) had included the New Drug Application (NDA) for the CAR-T cell therapy product axicabtagene ciloleucel injection (proposed) in the priority review program. The therapy is indicated for 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.

Yescarta® (axicabtagene ciloleucel) Injection (code FKC876) is a CD19-targeted autologous CAR-T cell therapy product, for which Fosun Kite has licensed the Yescarta technology from Kite Pharma and obtained authorization for localized manufacturing in China.

This product 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: Yescarta® (Axicabtagene Ciloleucel) Demonstrates High Rates of Response in Relapsed or Refractory Indolent Non-Hodgkin Lymphoma

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