Gilead Sciences' Kite unit on Monday reported that the Phase III ZUMA-7 trial, testing the CD19-directed CAR-T therapy Yescarta (axicabtagene ciloleucel) against standard care in second-line large B-cell lymphoma (LBCL), met its primary endpoint of event-free survival (EFS), as well as the secondary goal of objective response rate (ORR).
Top-line results suggest "a potential paradigm shift" in treating this disease, according to lead principal investigator Frederick Locke, noting that patient outcomes in the study after relapsing with front-line chemotherapy were "dramatically improved with rapid referral (to a CAR-T centre) and a single infusion of Yescarta, as compared to chemotherapy and consolidative autologous transplant."
ZUMA-7, which got under way in 2017 and was conducted under a special protocol agreement with the FDA, involved 359 adults with relapsed or refractory LBCL. Participants were randomly assigned to receive a one-time infusion of Yescarta or standard care, which consists of reintroducing immunochemotherapy, and then moving on to high-dose chemotherapy plus autologous stem cell transplant in responders.
Results after a median follow-up of two years showed an improvement of 60% for Yescarta on the primary endpoint of EFS, defined as time from randomisation to disease progression, commencement of new lymphoma therapy, or death from any cause. According to Kite, the interim analysis of overall survival (OS) indicated a "trend favouring" Yescarta, but the data are still immature, and more analyses are planned. The company noted that the two-year follow-up is the "longest…of any study in this setting."
Safety-wise, it said the results were "consistent with or lower than" Yescarta's known profile in third-line LBCL, with no new concerns emerging in this second-line setting. Kite added that Grade 3 or higher cytokine release syndrome and neurological events occurred at rates of 6% and 21%, respectively, in the Yescarta arm.
"Yescarta has been instrumental in transforming outcomes for patients with third-line LBCL," remarked Kite CEO Christi Shaw, adding "our goal has always been to bring the benefit of CAR-T cell therapy to more patients, earlier in their treatment, where the potential for benefit may be even greater." In 2017, the FDA authorised Yescarta for patients with LBCL after two or more lines of systemic treatment, with EU regulators following suit the following year.
The ZUMA-7 readout comes on the heels of Bristol Myers Squibb reporting that its CD19-directed CAR-T cell therapy Breyanzi (lisocabtagene maraleucel) also outperformed standard care in second-line LBCL. Top-line results from the Phase III TRANSFORM trial unveiled this month showed that Breyanzi led to significant improvement on the main goal of EFS, as well as on the secondary outcomes of complete response rate and progression-free survival. Breyanzi was approved in the US in February for LBCL patients who have received at least two other types of systemic treatment.
Meanwhile, sales of Yescarta, which carries a list price of $373,000, reached $160 million in the first quarter of 2021, up from $140 million in the year-ago period. Last week, Gilead partner Fosun Pharmaceutical said Chinese regulators approved Yescarta to treat LBCL in certain patients, making it the first CAR-T cell therapy authorised in that country.
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