Yescarta (axicabtagene ciloleucel), Kite Pharma’s CAR T-cell therapy, leads to a high rate of strong and sustained responses in adults with relapsed or refractory (resistant) follicular lymphoma, known as FL, or marginal zone lymphoma, called MZL, who received at least two prior therapy lines, according to interim data from a Phase 2 trial.
Both FL and MZL are subtypes of indolent non-Hodgkin’s lymphoma (NHL), which is characterized by a slow cancer growth and spread that can become more aggressive over time.
Notably, 92% of patients with evaluable efficacy data had responded to treatment after nearly 1.5 years since the single Yescarta dosing, and more than 60% were still responding.
“It is encouraging to see this level of response to CAR T-cell therapy in a heavily pretreated and multiply relapsed patient population, in whom response duration to other available therapies is expected to be short,” Caron A. Jacobson, MD, the principal investigator of the trial’s site at the Dana-Farber Cancer Institute, in Boston, said in a press release.
Jacobson also is the medical director of Dana-Farber’s immune effector cell therapy program and an assistant professor of medicine at Harvard Medical School.
The findings, “Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL),” were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, held virtually Dec. 5–8.
Based on these promising data, the U.S. Food and Drug Administration (FDA) has accepted and granted priority review to Kite Pharma’s supplemental biologics license application seeking the approval of Yescarta for the treatment of relapsed or refractory FL and MZL after two or more prior lines of therapy.
A final decision is expected no later than March 5, 2021. If approved, Yescarta would become the first CAR T-cell therapy available for relapsed or refractory indolent NHL, mimicking its previous FDA-approval, granted in 2017, for adults with large B-cell NHL who received at least two prior therapies.
“We’re excited about the potential role of Yescarta in indolent NHL and look forward to continuing to work with the FDA to bring it to these patients as soon as possible,” said Ken Takeshita, MD, Kite’s global head of clinical development.
Yescarta, developed by Gilead Sciences-owned Kite and formerly known as KTE-C19, is a type of immunotherapy that modifies a person’s own T-cells — a type of immune cell with anti-cancer activity — to fight cancer. The cells are collected and then engineered in the lab, after which they are expanded and infused back into the patient.
Specifically, Yescarta delivers T-cells engineered to recognize and kill cells containing CD19 — a protein found at high levels on certain malignant B-cells.
The ZUMA-5 Phase 2 trial (NCT03105336) is evaluating the safety and effectiveness of a single infusion of Yescarta in up to 160 adults with relapsed or refractory FL and MZL. Participants must have received at least two prior lines of therapy, including an anti-CD20 monoclonal antibody, which is targeted against B-cell antigens, and an alkylating chemotherapy, made from certain types of plants.
The study is recruiting participants at 18 clinical sites across the U.S. and one in France. For more information on contacts and locations, go here.
Its main goal is to assess the proportion of patients showing partial or complete responses to treatment. Also called complete remission, a complete response indicates the disappearance of all signs of cancer in response to treatment. Importantly, this does not always mean the cancer has been cured.
Secondary goals include the rate of complete responses, response duration, the time patients lived without signs of disease progression (progression-free survival), overall survival, and safety measures.
At the data cut-off date of Dec. 3, 146 participants — 124 with FL and 22 with MZL — with a median age of 61 years had been treated with Yescarta. Most (64%) had received three or more previous treatments.
Patients were followed for a median of 17.5 months (nearly 1.5 years), and 84 FL patients had at least one year of follow-up. A total of 104 (83.9%) participants (84 with FL and 20 with MZL) had evaluable data for the primary efficacy analysis.
The results showed that 92% of the evaluable patients responded to treatment, including 76% with complete responses. FL patients showed greater response rates (94% vs. 85%), including complete responses (80% vs. 60%), compared with MZL patients.
At the time of the analysis, 62% of patients had ongoing responses (64% in the FL patient group).
The median duration of response, progression-free survival, and overall survival were not reached. However, an analysis estimated that after one year, 72% of patients were still responding to treatment, 74% were still living without signs of disease progression, and 93% were alive.
Jacobson said that “the impressive durability following a one-time treatment of [Yescarta] is incredibly promising for relapsed/refractory patients, who are often at a higher risk for early progression.”
The safety analysis, including all 146 patients, showed that 86% of patients had a severe or worse adverse event.
Within this category, neurologic events occurred in 19% of participants (15% of FL patients and 41% of MZL patients), and cytokine release syndrome (CRS) in 7% (6% of FL and 9% of MZL). CRS is a serious inflammatory response triggered by the modified T-cells.
Most neurologic events and CRS of any severity were resolved by data cut-off. Three deaths were reported, with one being associated with CRS and therefore considered related to Yescarta.
Yescarta resulted in “considerable and durable clinical benefit” in adults with indolent NHL, including high rates of overall and complete responses, the researchers wrote in the abstract.
“As we continue to advance Kite’s cell therapy franchise, this analysis further demonstrates the practice-changing potential of Yescarta in additional hematologic malignancies,” said Takeshita.
