Kura Oncology announced clinical and regulatory updates for its lead drug candidate, tipifarnib, in angioimmunoblastic T-cell lymphoma, including data from the Company's ongoing Phase 2 clinical trial of tipifarnib in relapsed or refractory peripheral T-cell lymphoma. The updated interim data are being presented during an oral session today at the American Society of Hematology Annual meeting. As of the November 11 data cutoff date, a total of 26 patients with relapsed or refractory AITL were enrolled in all stages of the trial. Among the 20 patients evaluable for efficacy, five achieved a complete response and five achieved a partial response, for an objective response rate of 50% on an evaluable basis and 38% on an intent-to-treat basis. In addition, three patients experienced disease stabilization. Patients had a median of three prior regimens. Next-generation sequencing of 19 available patient biopsies showed that 10 carried C336R/Q386E variants in the killer-cell immunoglobulin-like receptor 3DL2, an immune checkpoint receptor. Four of the 10 patients with KIR3DL2 variants achieved a CR and three achieved a PR, for a CR rate of 40% and an ORR of 70%. This compares to a CR rate of 11% and an ORR of 22% among the nine AITL patients with KIR3DL2 wild type. Tipifarnib was generally well-tolerated in this Phase 2 trial, with adverse events consistent with its known safety profile, Kura said. "We are encouraged by our growing body of data for tipifarnib in AITL," said Antonio Gualberto, Head of Development and Chief Medical Officer of Kura Oncology. "We believe these data support our efforts to expand the development of tipifarnib beyond our initial focus in HRAS mutant solid tumors and could enable registrational strategies in multiple CXCL12-dependent hematologic and solid tumor indications."

Fate Therapeutics announced new in vivo preclinical data for FT596, its off-the-shelf, multi-antigen targeting natural killer cell product candidate derived from a clonal master engineered induced pluripotent stem cell line. The data were featured during the American Society of Hematology Meeting. New preclinical data showed that FT596 "administered as a monotherapy exhibited durable tumor clearance and extended survival in vivo similar to primary CAR T cells in a humanized mouse model of CD19+ lymphoma. Additionally, when combined with the anti-CD20 monoclonal antibody rituximab, FT596 showed enhanced killing of CD20+ lymphoma cells in vivo as compared to rituximab alone. These data confirm previously presented in vitro findings that demonstrate the unique multi-antigen targeting functionality of FT596, and the product candidate's potential to effectively overcome CD19 antigen escape," the company said. Fate also announced that, in preparation for Phase 1 initiation, it had recently completed GMP production of FT596. In a single small-scale manufacturing campaign, the company produced over 300 cryopreserved, infusion-ready doses of FT596 at a cost of approximately $2,500 per dose.

Autolus Therapeutics announced new data highlighting progress on AUTO3, the first-in-human bicistronic CD19 and CD22 CAR, in patients with relapsed/refractory diffuse large B-cell lymphoma and pediatric acute lymphoblastic leukemia. The data were presented at the American Society of Hematology Annual Meeting. In the dose escalation phase, 16 patients were treated, with 4 patients dosed at 50 x 106 cells without pembrolizumab; 11 patients were dosed at escalating doses of AUTO3 with pembrolizumab administered at day 14 as follows: 3 at 50 x 106 cells, 4 at 150 x 106 cells, and 4 at 450 x 106 of AUTO3; and 1 patient was dosed with 450 x 106 cells with pembrolizumab administered 1 day before AUTO3 infusion. Fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing greater than or equal to Grade 3 cytokine release syndrome with primary infusion and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids, the compamny said. There were no pembrolizumab immune-related toxicities and the majority of grade 3 or higher adverse events were hematological. Across all tested doses 5 patients achieved a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months. All CRs were achieved without need for steroid or tocilizumab-based management of the patients or ICU level care, it added. Among the 10 CAR T-naive patients, at a median follow-up time of 9.7 months, 9 of 10 patients achieved a complete response, and 8 of 10 achieved complete molecular remission by PCR. Estimated overall survival at 12 months was 100%. There are 2 ongoing patients in complete molecular remission at 12 and 15 months post-AUTO3 infusion, respectively. The most common cause of relapse was due to loss of CAR T-cell persistence. The median persistence of CAR-T cells in blood was 170 days.

Ziopharm Oncology announced the presentation of pre-clinical data of Rapid Personalized Manufacture, in the "Adoptive Immunotherapy: Mechanisms and New Approaches" session at the American Society of Hematology Annual Meeting. "These pre-clinical data demonstrate that T cells genetically modified using DNA plasmids from the Sleeping Beauty system to express TCR with membrane bound IL-15 (mbIL15) exhibit anti-tumor effects," said Drew Deniger, leader of Ziopharm's TCR program. "These data build on our approach to reduce the cost and complexity of T-cell therapies. We have previously demonstrated that mbIL15 can be combined with a CD19-specific chimeric antigen receptor (CAR) to shorten the time to generate clinical-grade T cells and an IND is cleared to evaluate this RPM technology."