Kite Pharma recently reported positive data from an interim analysis of ZUMA-1, a clinical trial assessing the safety and efficacy of KTE-C19 in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL).
KTE-C19 is an investigational treatment in which T-cells from patients are genetically modified to express a chimeric antigen receptor (CAR) aimed at targeting CD19, a protein that is found at the cell surface in leukemias and B-cell lymphomas.
Kite is currently running three single-arm, multi-center trials to support the development of KTE-C19:
- ZUMA-1 (NCT02348216), a Phase 1/2 study assessing KTE-C19 in patients with refractory, aggressive non-Hodgkin’s lymphoma (NHL), including refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL).
- ZUMA-2 (NCT02601313), a Phase 2 study assessing KTL-C19 in patients with relapsed or refractory mantle cell lymphoma
- ZUMA-3 (NCT02614066), a Phase 1/2 study evaluating KTL-C19 in adult patients with relapsed or refractory acute lymphocytic leukemia.
The ZUMA-1 trial, a multicenter Phase 1/2 assessing the safety and efficacy of KTE-C19 in patients with refractory, aggressive NHL, divided enrolled patients into two cohorts. Cohort 1 included patients with DLBCL, and cohort 2 included patients with TFL and PMBCL. All received one single infusion of KTE-C19 following three days of chemotherapy.
A Phase 2 interim analysis included the first 51 patients in cohort 1 and 11 patients from cohort 2, and found that the study met its primary endpoint, with an objective response rate (ORR) of 76 percent in DLBCL patients, including 47 percent complete remissions (CR). At three months follow-up, ORR for these patients was 39 percent and CR 33 percent, while in all NHL patients evaluated, ORR was 44 percent and CR 39 percent, the company reported in a press release.
The most commonly reported adverse events (grade 3 or higher) were neutropenia, anemia, febrile neutropenia, thrombocytopenia, and encephalopathy, as well as cytokine release syndrome and neurological toxicity. Treatment with KTE-C19 caused two deaths related with adverse events.
These results are consistent with the data from the Phase 1 portion of the trial, as well as from a National Cancer Institute (NCI) trial based on the same CAR construct, a low-dose chemotherapy regimen, and Kite’s proprietary manufacturing process (Kochenderfer ASCO 2016).
“ZUMA-1 enrolled patients with chemorefractory aggressive NHL, a disease that is very difficult to treat. The combined CR rate of 39 percent at three months is very exciting as it represents nearly a five-fold increase from the CR rate of 8 percent seen in the SCHOLAR-1 study in a similar patient population,” Jeff Wiezorek, MD, senior vice president of Clinical Development, said in a press release. “ZUMA-1 is the largest CAR-T study reported in NHL. We were able to manufacture KTE-C19 for 99 percent of patients enrolled in the study, and successfully handle the study logistics and adverse event management at over 20 sites, most of which had no prior experience in CAR-T therapy.”
Kite will seek regulatory approval of KTE-C19 for patients with DLBCL, TFL and PMBCL based upon the combined results of both cohorts.
Supplementary results from this pre-specified interim analysis will be submitted for presentation at a future medical meeting. The primary analysis of 101 patients with chemorefractory aggressive NHL (DLBCL, TFL and PMBCL) will incorporate around six months of follow-up, and is anticipated for the first quarter of 2017.
“We are grateful to the study participants and investigators who have made this important research possible. For patients with aggressive NHL, every day matters and a new treatment option like KTE-C19 is desperately needed,” said Arie Belldegrun, MD, FACS, chairman, president and chief executive officer of Kite. “I am proud of what we have achieved to date and excited to apply our advanced learnings from ZUMA-1 to our ongoing clinical development programs to bring continued innovation to patients and the scientific community at large.”