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."

Karyopharm Therapeutics announced that four posters relating to Xpovio and eltanexor will be presented at the American Society of Hematology Annual Meeting. The four posters include: updated data from the Kyprolis arm of the Phase 1b/2 Stomp study evaluating selinexor in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; new data from the Revlimid plus selinexor arm of the Stomp study evaluating this combination in patients with newly diagnosed multiple myeloma; encore data highlighting the previously disclosed comparison of patients in the Storm study, Karyopharm's Phase 2b study evaluating Xpovio in patients with heavily pretreated, triple class refractory multiple myeloma, to matched patients from the Mamouth study; and new Phase 1/2 data evaluating eltanexor in patients with higher-risk myelodysplastic syndrome.

Regeneron Pharmaceuticals announced initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancer cell. Results were presented today at the American Society of Hematology Annual Meeting from the first two dose groups. Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment. Responses were observed in 4 of 7 patients, including 3 of 4 in the 6 mg dose group. In the 6 mg dose group, 2 patients were also minimal residual disease negative, meaning that no cancer cells were detectable in their bone marrow. "We are encouraged to see promising, rapid clinical activity even at the initial two doses of REGN5458 in heavily pretreated patients with multiple myeloma. Two patients achieved the high bar of MRD negativity, and another patient attained a very good partial response despite entering the trial with difficult-to-treat plasmacytomas outside of the bone marrow," said Israel Lowy, Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. "We are actively recruiting patients into higher dose groups in this trial and look forward to sharing further results in 2020. In addition, we have also initiated a clinical trial for our second BCMAxCD3 bispecific, REGN5459, which has different binding characteristics."

Blueprint Medicines announced initial data from the Phase 2 Pioneer clinical trial of avapritinib in patients with indolent systemic mastocytosis. Initial data from the dose-finding Part 1 of trial showed "rapid and robust reductions" in serum tryptase, a measure of mast cell burden, in patients treated with 25 mg, 50 mg or 100 mg of avapritinib once daily, the company said. All dose levels of avapritinib tested were well-tolerated, and no patients discontinued treatment due to an adverse event, it added.. The results will be presented today in a poster presentation at the American Society of Hematology Annual Meeting. At baseline, all patients had symptomatic disease despite best available therapy. Median Indolent SM Symptom Assessment Form total symptom score was 52. Patients were taking a median of three medications to treat their disease. Mean serum tryptase was 84 micrograms per liter. Across all avapritinib dose cohorts, reductions in serum tryptase were robust, occurred rapidly and were sustained in patients treated up to 30 weeks. The placebo cohort showed no change in serum tryptase at 12 weeks. All doses of avapritinib tested were well-tolerated, and most reported AEs were Grade 1 or 2, according to Blueprint. Across all avapritinib cohorts, five patients had Grade 3 AEs, and no patients had serious AEs. In patients treated with placebo, two patients had Grade 3 AEs, and two patients had serious AEs. There was one Grade 3 cognitive effect reported in the 100 mg cohort. The event resolved following dose modification, and the patient remained on therapy as of the data cutoff date. No patients discontinued treatment due to an AE. Blueprint plans to submit a new drug application to the FDA for avapritinib for the treatment of patients with advanced SM in Q1 of 2020.

Syros Pharmaceuticals announced that it has "discovered and validated" a novel fetal hemoglobin repressor, Nuclear Factor I X, using its gene control platform. "The finding sheds light on how the gamma-globin gene, which leads to the production of fetal hemoglobin, is controlled and points to new potential targets for therapeutic intervention in sickle cell disease," according to the company. These data will be presented in an oral presentation tomorrow at the American Society of Hematology Annual Meeting. The data showed: Increases in expression of gamma-globin mRNA comparable to known fetal hemoglobin repressors; Detectable levels of fetal hemoglobin in nearly 100% of cells, compared to 16% of cells when the NFIX gene was not knocked down; Increases in total fetal hemoglobin levels to 40%, exceeding levels that are associated with a functional cure in sickle cell patients with HPFH, according to Syros.

Genentech, a member of Roche Group, announced updated data from two pivotal Phase III Venclexta studies that highlight Venclexta combination treatments as chemotherapy-free, fixed-duration options that achieve minimal residual disease negativity, in people with chronic lymphocytic leukemia. The pivotal Phase III CLL14 study evaluated the combination of Venclexta plus Gazyva in people with previously untreated CLL, who had co-existing medical conditions. At a median follow-up of more than three years, when all patients had been off therapy for a minimum of two years, Venclexta plus Gazyva showed high response rates, including MRD-negativity. The company said higher rates of MRD-negativity in peripheral blood and bone marrow were observed at the end of treatment in people treated with Venclexta plus Gazyva versus Gazyva plus chlorambucil, respectively. MRD-negativity indicates that no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells, it added. MRD-negativity was observed in 42% of people treated with Venclexta plus Gazyva who achieved a complete response in the peripheral blood, and 14% of people treated with Gazyva plus chlorambucil. Further, the pivotal Phase III Murano study evaluated the combination of Venclexta plus Rituxan in relapsed or refractory CLL. Results showed that Venclexta plus Rituxan significantly reduced the risk of disease progression or death by 81%, Genentech reported. Venclexta plus Rituxan also reduced the risk of death by 59%.