ASH | Gilead Sciences Reports Positive Progress for Two CAR-T Therapies

Recently, Kite Pharma, a subsidiary of Gilead Sciences, announced at the 61st ASH Annual Meeting that its CD19-targeted CAR-T therapy, KTE-X19, achieved positive results in the pivotal Phase 2 ZUMA-2 clinical trial. In the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL),67% of patients achieved complete remission after one treatment.Based on this data, Gilead Sciences expects to submit a Biologics License Application (BLA) to the U.S. FDA by the end of this year.

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that arises from malignant transformation of cells in the mantle zone of lymph nodes and typically affects men over the age of 60. Although multiple therapies are currently available for this cancer, patients ultimately develop resistance to existing treatments, necessitating innovative therapeutic options. Patients with MCL enrolled in the ZUMA-2 trial had previously received five prior lines of therapy, including chemotherapy, anti-CD20 monoclonal antibody therapy, and the BTK inhibitors ibrutinib or acalabrutinib, but their disease became refractory or relapsed.

KTE-X19 is an autologous anti-CD19 CAR-T cell therapy. It utilizes the XLP manufacturing process, which incorporates T-cell selection and lymphocyte enrichment. For certain B-cell malignancies with evidence of circulating lymphoblasts, lymphocyte enrichment is a critical step in CAR-T cell therapy manufacturing. KTE-X19 has previously received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) and PRIME medicine designation from the European Medicines Agency (EMA).

Results from the ZUMA-2 trial demonstrated that among 60 evaluable patients with mantle cell lymphoma (MCL), 67% achieved complete response. At a median follow-up of 12.3 months, 57% of patients maintained their response. Among the initial cohort of 28 patients with at least 24 months of follow-up, 43% remained alive and in sustained remission without requiring additional therapy. The estimated 12-month progression-free survival and overall survival rates were 61% and 83%, respectively.

“This result represents an important milestone for both Kite and the MCL patient community,” said Christi Shaw, Chief Executive Officer of Kite. “KTE-X19 has the potential to become the second CAR-T therapy from our industry-leading cell therapy development program, and it is the first CAR-T therapy for patients with relapsed or refractory MCL. We look forward to working with the FDA and other regulatory authorities to make KTE-X19 available to patients as soon as possible.”

Yescarta Real-World Treatment Outcomes Are Comparable to Clinical Trial Results

Furthermore, Kite also presented real-world data on its first CAR-T therapy, Yescarta, at the ASH annual meeting. This study, conducted in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR), demonstrated that in the treatment of relapsed or refractory large B-cell lymphoma,The real-world outcomes achieved with Yescarta were comparable to those observed in the ZUMA-1 clinical trial.

Specifically, this analysis included a total of 533 patients, with a higher proportion of elderly patients (aged ≥65 years) at 37% and a higher proportion of patients with two or three relapses of lymphoma at 36%. In contrast, these figures in the ZUMA-1 trial were 25% and 11%, respectively.

Follow-up results at 6 months and beyond indicate that, among the 326 patients evaluable for efficacy who received a single infusion of Yescarta,The best objective response rate (ORR) reached 84%, with 66% of patients achieving complete remission (CR). In patients younger than 65 years old, the ORR was 80%. In patients aged 65 or older, the ORR was 92%. The complete remission rates for the two groups were 62% and 72%, respectively.In terms of safety, the risk of grade 5 adverse events (cytokine release syndrome and neurotoxicity) is approximately 1%, which is also similar to that observed in the ZUMA-1 clinical trial.

“In this post-approval analysis, the efficacy and safety results, which are similar to those observed in the ZUMA-1 trial, are highly encouraging. Appropriate patients with relapsed or refractory large B-cell lymphoma are expected to benefit from Yescarta,” said Dr. Marcelo Pasquini, Senior Scientific Director at CIBMTR and co-leader of this study. “Early real-world data, including side effect profiles, validate the potential of Yescarta in older, high-risk, and more difficult-to-treat patients—populations that clinicians frequently encounter.”

Ms. Christi Shaw, CEO of Kite, also pointed out that these results can promote more doctors to bring this CAR-T therapy to patients in the real world, thereby benefiting more patients.

References:

[1] Kite Presents Positive Results From Pivotal ZUMA-2 Trial in Relapsed or Refractory Mantle Cell Lymphoma. Retrieved December 9, 2019, from http://investors.gilead.com/news-releases/news-release-details/kite-presents-positive-results-pivotal-zuma-2-trial-relapsed-or

[2] Kite and the CIBMTR® Present Positive Findings From Real-World Use of Yescarta® (Axicabtagene Ciloleucel) in Relapsed or Refractory Large B-Cell Lymphoma. Retrieved December 19, 2019, from https://www.gilead.com/news-and-press/press-room/press-releases/2019/12/kite-and-the-cibmtr-present-positive-findings-from-realworld-use-of-yescarta-axicabtagene-ciloleucel-in-relapsed-or-refractory-large-bcell-lymph

Original Title: ASH | Double Good News for Gilead Sciences: Positive Progress in Two CAR-T Therapies

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