Kite Pharma has enrolled the first patient in a Phase 1b/2 study evaluating the safety and efficacy of KTE-C19, a CAR T-cell therapy, in combination with Genentech’s anti-PD-L1 immunotherapy atezolizumab, for the treatment of chemorefractory diffuse large B-cell lymphoma (DLBCL).
KTE-C19, Kite Pharma’s lead candidate, is a novel treatment in which patients’ T-cells are genetically modified to express a chimeric antigen receptor (CAR) that targets the CD19 molecule, widely expressed at the surface of B-cell lymphomas and leukemias.
Cancer cells can inhibit T-cell activity through the production of immune checkpoint molecules. PD-L1, particularly, which is associated with high-risk DLBCL and poor outcomes in patients, interacts with the PD-1 molecule found at the surface of T-cells (and KTE-C19 cells) to limit their effectiveness.
It is possible that a combination strategy may offer a synergistic effect; inhibiting PD-L1 with atezolizuma may boost and extend KTE-C19’s activity and proliferation.
The ZUMA-6 trial (NCT02926833), an open-label study designed to assess the safety and efficacy of KTE-C19 in combination with atezolizumab in subjects with refractory DLBCL, will be separated into two distinct phases. The Phase 1b portion will assess the combination’s safety, by measuring the incidence of dose-limiting adverse events. Phase 2 will mainly assess the combination’s safety and efficacy, by measuring the overall response rate.
ZUMA-6, which is expected to enroll 31 DLBCL patients, is currently recruiting participants at the H. Lee Moffitt Cancer Center in Florida, and at the University of Texas MD Anderson Cancer Center.
“The ZUMA-6 combination study is a core element of our broad strategy to optimize KTE-C19 treatment outcomes and to significantly extend the important potential benefits of KTE-C19 monotherapy,” David Chang, MD, PhD, Kite’s executive vice president, Research and Development, and chief medical officer, said in a press release. “We view the scientific rationale for this combination study as compelling and look forward to advancing the study based on our extensive clinical experience.”
KTE-C19 is also being evaluated in four single-arm, open-label, multicenter studies (ZUMA-1, ZUMA-2, ZUMA-3 and ZUMA-4):
- ZUMA-1 (NCT02348216) is a Phase 1/2 studying 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) is a Phase 2 study in patients with relapsed/refractory mantle cell lymphoma,
- ZUMA-3 (NCT02614066) is a Phase 1/2 study in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL),
- ZUMA-4 (NCT02625480) is a Phase 1/2 study for pediatric ALL.
Kite and Genentech began their clinical collaboration in March 2016 to evaluate the safety and efficacy of KTE-C19 in combination with atezolizumab.
Atezolizumab, under the brand name Tecentriq, was approved by the U.S. Food and Drug Administration to treat urothelial carcinoma, the most common form of bladder cancer, in May. KTE-C19 was designed a “breakthrough therapy” by the FDA, speeding its development, in December 2015.
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