Gilead Sciences’ Kite Pharma does not expect CAR-T therapy Yescarta to stop at the late-line therapy stage for lymphoma. The company now has data supporting a potential move earlier in the treatment sequence, putting it on a collision course with Bristol Myers Squibb.
Compared with standard of care in large B-cell lymphoma (LBCL) patients who had failed just one prior therapy, Yescarta showed a whopping 60.2% improvement in the so-called event-free survival (EFS) benefit goal, which measures the time to disease progression, start of a new drug or death, Kite said Monday.
The phase 3 win, from the ZUMA-7 trial, came on the heels of Bristol Myers Squibb touting a similar success for rival CAR-T drug Breyanzi. BMS hasn’t disclosed the magnitude of the event-free survival benefit, but the two drugs now look on track to duke it out in second-line LBCL.
The EFS showing exceeded Kite’s original expectation of a 33% improvement, Kite CEO Christi Shaw said during an interview.
Yescarta also showed it could significantly shrink tumors in more patients than did current standard treatment, which involves Roche’s Rituxan-containing salvage therapy and high-dose chemotherapy followed by stem cell transplant in responders.
Investigators also observed a trend of life-extension advantage for Yescarta, but the data are still immature. Kite said it plans to follow patients longer to assess their overall survival.
In terms of safety, cytokine release syndrome of grade 3 or higher happened in 6% of patients, with a median onset of three days. Twenty-one percent of patients experienced neurological events at grade 3 or above.
Frederick Locke, M.D., lead principal investigator of the ZUMA-7 trial, said Yescarta “dramatically improved patients’ outcomes and could make for a potential “paradigm shift” for LBCL.
Both Breyanzi and Yescarta are CD19-directed CAR-T therapies that thus far have been allowed as a therapy only in third- or later-line LBCL. The difference is that Yescarta has been treating patients since late 2017, while Breyanzi just scored its FDA go-ahead in February.
Breyanzi reported a top-line win earlier than Yescarta likely because the BMS drug’s phase 3 TRANSFORM trial recruited 175 patients, fewer than the 359 enrolled to ZUMA-7. Yescarta's positive news today came from a final analysis of the EFS data after about two years of follow-up, while Breyanzi's announcement a few days ago came from an interim analysis, Frank Neumann, M.D., Ph.D., Kite's head of clinical development, pointed out during the interview.
An approval in the second-line setting would add 14,000 U.S. patients to Yescarta's target market on top of the roughly 8,000 eligible patients in the current third-line-plus indication, Shaw said.
The good thing for Yescarta is that the FDA has already signed off on its trial design upfront, Shaw said, so “we don't have to have a lot of discussions about the validity of this study, which can take some time.”
Yescarta is currently the market-leading CD19 CAR-T drug, with sales of $160 million in the first quarter, slightly ahead of Novartis’ rival Kymriah, which brought in $151 million during the same period. The Kite drug recently snagged a first-in-class FDA green light to treat patients with relapsed or refractory follicular lymphoma, and it just became the first CAR-T therapy approved in China through a Kite joint venture with Fosun Pharma.
Second-line LBCL isn’t where Kite’s Yescarta ambition stops, either. The company reported encouraging data from a phase 2 trial of Yescarta in newly diagnosed lymphoma patients at last December's ASH annual meeting. The ZUMA-12 trial found that Yescarta triggered a response in 85% of patients, including eradicating signs of cancer in 74% of them, after a median follow-up of 9.3 months.
The company has another CD19 CAR-T therapy, Tecartus, which is being used for relapsed or refractory mantle cell lymphoma and is awaiting an FDA decision in adult acute lymphoblastic leukemia.
Editor's Note: The story has been updated with additional comments from Christi Shaw and Frank Neumann.