Kite Pharma’s bicistronic CAR T-cell therapy hit the main goal of a phase 1a trial, with zero dose-limiting toxicities (DLTs) occurring in patients with advanced B-cell lymphoma (BCL). The therapy was also tied to a complete response (CR) rate of 78% for patients receiving the highest cell therapy dose.
“This, to me, is a community drug where we can reach more patients and provide more opportunity for a potential cure,” Cindy Perettie, executive vice president and global head of Gilead Sciences' Kite, told Fierce Biotech at the American Society of Clinical Oncology conference in Chicago.
The company is currently deciding between two manufacturing methods for the therapy, with the hope of moving the asset into pivotal trials soon.
The open-label, early-stage trial evaluated 37 patients who received KITE-363, an anti-CD19/CD20 CAR therapy. Patients all had relapsed or refractory (R/R) BCL after receiving two or more lines of therapy, and 34 of those patients had large B-cell lymphoma (LBCL).
After receiving lymphodepleting chemotherapy—a normal regimen used before many cell therapies to make room for new T cells—patients were given KITE-363 across three different dose levels.
On the safety side, no DLTs were recorded up to 28 days after infusion, hitting the primary goal of the first part of the study.
Diving deeper into the safety findings, no grade 4 or 5 cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) occurred.
One grade 3 CRS event was reported in a patient who had nodular lymphocyte-predominant Hodgkin lymphoma, a rare type of Hodgkin lymphoma. Meanwhile, three grade 3 ICANs cases were recorded, two of which were in patients receiving the highest dose level.
Overall, ICANS events had a median duration of five days, while CRS events lasted a median of five days.
“Interestingly, ICANs today for the products on the market will take nine [or] 10 days, sometimes two weeks, to resolve. These resolved within one to five days,” Perettie said. “We're looking at the translational data to try to understand it.”
A physicians care model revealed that the ICANs cases were ongoing for about 24 hours and then mostly resolved, she explained.
“We need to figure that out, but that's great news,” the Kite leader said, adding that if the therapy can produce a safety profile with only grade 1 and 2 events, it could be delivered in an outpatient setting.
“We're excited. We think this could be an outpatient drug,” Perettie said. “In phase 1, you study the sickest patients. So, the patients that come on trial are patients that have failed all therapies.”
“As we move into earlier lines, as we go into the pivotal trials—we're going to be going into third-line and second-line lymphoma as an example—you expect that safety will improve,” she continued. “You expect that efficacy could improve.”
Overall, adverse events (AEs) classified as grade 3 or higher occurred in 76% of patients, with serious AEs observed in 49% of patients.
Six patients in the trial died. Five deaths were due to disease progression, and one was due to myelodysplastic syndrome concurrent with LBCL relapse, unrelated to KITE-363.
In the phase 1b dose-expansion portion of the trial, the primary endpoint is objective response rate measured for up to 15 years.
In a data cut taken at a median follow-up of 7.3 months, ORR in CAR-naive patients who received the highest dose of KITE-363 was 87%, while the CR rate was 78%.
The median duration of response was not yet reached.
The autologous drug is bicistronic, which means the T cells are designed to express two different CARs at the same time. KITE-363 targets CD19 and CD20, costimulatory domains that are often associated with safety, Perettie said.
The therapy takes five days to manufacture, but Kite is currently testing out the same CAR that is manufactured in three days with more juvenile cells. In July, the company expects to decide which version it intends to advance into pivotal studies.