On December 7, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported that results from its CD19-specific CAR T-cell therapy programs were presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Press release, Ziopharm, DEC 7, 2015, View Source [SID:1234508482]). The presentation (Abstract 862), titled "Pre-Emptive Donor Lymphocyte Infusion with CD19-Directed, CAR-Modified T Cells Infused after Allogeneic Hematopoietic Cell Transplantation for Patients with Advanced CD19+ Malignancies" was presented by lead author Partow Kebriaei, M.D., Associate Professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in an oral session, and is available at www.ziopharm.com. The investigational therapies infusing T cells genetically modified to express a CD19-specific chimeric antigen receptor (CAR), described in the presentation, were exclusively licensed to ZIOPHARM and its collaboration partner, Intrexon Corporation (NYSE:XON), through an agreement with MD Anderson.

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"This study, which was initially designed to test the safety and tolerability of the Sleeping Beauty platform, a system for the non-viral genetic modification of cells, appears to show a survival benefit with a doubling of overall survival compared to historical controls," said Dr. Richard Champlin, Chair, Department of Stem Cell Transplantation and Cellular Therapy at MD Anderson. "This is the measure of clinical success for a post-transplant therapy, where the contribution of either treatment is difficult to discern in early follow-up. Also promising was the absence of GvHD among HLA-mismatched CAR+ T-cell recipients, even at large doses, which supports infusing third-party T cells."

In the two separate trials described in Dr. Kebriaei’s presentation, patient-derived (autologous) or donor-derived (allogeneic) CAR-modified T cells targeting CD19 were administered to recipients with advanced CD19+ malignancies after hematopoietic stem-cell transplantation (HSCT). The studies employed the Sleeping Beauty system, a cost-effective non-viral two plasmid electroporation method to stably express CAR in T cells.

Seven patients with advanced non-Hodgkin lymphoma (NHL) were treated with autologous cells, all of whom remained alive and six of whom remained in complete remission at a median 25.5 months of follow-up translating to a three-year progression free survival (PFS) of 83% and a three-year overall survival (OS) of 100%.

Nineteen patients with advanced acute lymphoblastic leukemia and NHL were treated with allogeneic T cells. One-year PFS among these patients was 53% and one-year OS was 63%. Among eight patients who received donor-derived T cells after haploidentical HSCT, all remained alive and six remained in complete remission after a median of 5.2 months of follow up, translating to a one-year PFS of 75% and OS of 100%.

No infusion related or late toxicity was observed in any recipients. A mild elevation in cytokines was observed, without cytokine storm. Autologous and allogeneic cells survived an average of 201 and 51 days, respectively.

A graft-versus-host disease (GvHD) rate of 11% was observed among recipients receiving donor-derived CAR+ T cells which did not differ from controls. Because of this low rate of GvHD, a complication associated with allogeneic HSCT, administration of up to 108/m2 genetically modified haploidentical T cells was possible. This lays the groundwork for infusing HLA-mismatched CAR+ T cells as an off-the-shelf broadly-accessible therapeutic.

"Sleeping Beauty, which is among the fastest technologies to go from bench to bedside, was a critical innovation of this trial," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "In addition to demonstrating safety and durable responses, it provides us a pathway for testing new CARs, co-expressing CAR with other molecules, and to do so at relatively low cost in the setting of both patient-derived and third-party derived products. We look forward to the new trial initiated at MD Anderson using Sleeping Beauty-modified T cells expressing a next-generation CD19-specific CAR in active CD19+ lymphoid malignancies."

Results from the haploidentical population were also presented separately in an oral presentation, titled "Donor-derived CD19-specific CAR+ T-cell therapy after haploidentical hematopoietic stem-cell transplantation," by Dr. Cooper, at the Haplo2015 Symposium, December 3, 2015, in Orlando, Florida. The presentation is available at www.ziopharm.com.

On December 7 AstraZeneca reported plans to test a digital support service for women undergoing treatment for recurrent platinum-sensitive high-grade ovarian cancer in clinical trials of cediranib plus olaparib (Press release, AstraZeneca, DEC 7, 2015, https://www.astrazeneca.com/our-company/media-centre/press-releases/2015/AstraZeneca-and-Voluntis-to-test-companion-mobile-app-in-ovarian-cancer-studies-07122015.html [SID:1234508600]). Voluntis has developed the service in close clinical collaboration with AstraZeneca and the US National Cancer Institute (NCI). It is delivered through a smartphone app paired with a web portal to help clinicians and patients manage side effects of hypertension and diarrhoea sometimes associated with combination therapy with cediranib and olaparib. Such side effects are traditionally described to care teams through manual, time-consuming and non-digitised channels.

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The app will be tested as a companion device in three separate clinical trials sponsored by the NCI beginning in the first quarter of 2016, under a Cooperative Research and Development Agreement between the NCI and AstraZeneca. This approach illustrates a clear focus on understanding the patient journey when developing therapeutic solutions. The service will also serve as a pilot within AstraZeneca’s broader strategy of using digital technology to complement treatment and to improve patient outcomes.

Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca, said: "Empowering patients with this smartphone-based app gives them greater control of their treatment and management of their response. The support it provides can further reduce medication dose modification and discontinuation rates and help maintain patients on therapy to improve their treatment outcome."

Pierre Leurent, Chief Executive Officer of Voluntis, said: "We are delighted to be partnering with AstraZeneca for this project. AstraZeneca has a strong focus on the use of companion devices in drug development. Their approach, combined with our technological, medical and regulatory expertise provides the perfect synergy to create a personalised therapeutic solution that goes beyond the pill to best serve the needs of patients and their health care providers."

NOTES TO EDITORS

About cediranib

Cediranib is a highly potent, selective, orally-administered inhibitor of VEGF-1, -2 and -3 receptors. It has been shown to inhibit angiogenesis and lymphangiogenesis in the vascularization of platinum sensitive tumor types. In July 2015, cediranib filing was accepted by the European Medicines agency and awarded Orphan Drug status for the treatment of platinum sensitive relapse ovarian cancer. Cediranib also in development, in combination with Lynparza (olaparib), for platinum sensitive relapse ovarian cancer and platinum resistant relapse ovarian cancer.

About olaparib

Olaparib is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumour types with DNA repair deficiencies. Olaparib is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe, with ongoing regulatory submissions across multiple markets. In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway.

About Voluntis

Pioneering therapeutic companion software, Voluntis innovates healthcare by embedding connectivity in therapeutics and medical intelligence in software. Dedicated to managing chronic conditions, Voluntis’ companion software aim to enable treatment personalisation, to support team-care coordination and to improve real-world outcomes. Harnessing its proprietary technology, Voluntis has developed digital solution for diabetes, respiratory diseases, cancer, anticoagulation treatments and haemophilia. Voluntis is headquartered in Paris, France, and has offices in Boston, USA. For more information, visit www.voluntis.com.

On December 7, 2015 Kite Pharma, Inc. (Nasdaq:KITE) reported that it has initiated a phase 1/2 clinical study of KTE-C19 (ZUMA-4) for the treatment of pediatric and young adult patients with r/r ALL (Press release, Kite Pharma, DEC 7, 2015, View Source [SID:1234508442]). KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a chimeric antigen receptor designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias.

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"With the commencement of ZUMA-4, Kite has achieved its goal of initiating four company-sponsored trials this year for its lead product candidate, KTE-C19," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "Our ZUMA trials are investigating critical needs in non-Hodgkin lymphoma (NHL) and ALL in patients with advanced, relapsed or refractory disease who have few or no other treatment options."

"We are enthusiastic about the possibility that KTE-C19 could safely put children and young adults who have persistent ALL despite multiple prior standard therapies into complete remissions," said internationally recognized leukemia expert Leonard S. Sender, M.D., Medical Director and Division Chief, and ZUMA-4 trial investigator, at Children’s Hospital of Orange Country. "Kite has done an outstanding job advancing immunotherapy for testing in multiple multi-center trials, and we are thrilled to offer this trial to our young patients and their families."

ZUMA-4 will proceed as a single-arm, open-label, multi-center study in patients with ALL whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation. The phase 1 portion of ZUMA-4 will assess the safety of KTE-C19, and the phase 2 portion will assess efficacy and safety. The study will target to enroll a total of 75 patients. Additional details about this study will be available on ClinicalTrials.gov.

On December 7, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported the outcomes of two Phase 3 cancer studies (MAESTRO and TH-CR-406/SARC021) of evofosfamide (previously known as TH-302), an investigational hypoxia-activated prodrug, which is being evaluated for first-line treatment of advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma, in combination with chemotherapy (Press release, Threshold Pharmaceuticals, DEC 7, 2015, View Source [SID:1234508463]). The Phase 3 studies are being conducted under Threshold’s collaboration with Merck KGaA, Darmstadt, Germany.

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In the Phase 3 MAESTRO study, patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma treated with evofosfamide in combination with gemcitabine did not demonstrate a statistically significant improvement in overall survival (OS) compared with gemcitabine plus placebo (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.71 – 1.01; p=0.0589).

In the Phase 3 TH-CR-406/SARC021 study being conducted in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC), patients with locally advanced unresectable or metastatic soft tissue sarcoma treated with evofosfamide in combination with doxorubicin did not demonstrate a statistically significant improvement in OS compared with doxorubicin alone (HR: 1.06; 95% CI: 0.88 – 1.29).

Patient safety was monitored in MAESTRO and TH-CR-406/SARC021 by independent data monitoring committees throughout the conduct of each study. No new clinically significant safety findings were observed.

Detailed results from both studies will be submitted for presentation at upcoming international scientific meetings and for publication in peer-reviewed journals. Threshold will not be pursing further development of evofosfamide in soft tissue sarcoma and pancreatic cancer.

"We are surprised and disappointed that these studies did not show that evofosfamide could extend the lives of patients with these two difficult-to-treat diseases," said Barry Selick, Ph.D., Chief Executive Officer at Threshold. "Threshold has been pursuing evofosfamide for over ten years in collaboration with world-class scientists and investigators throughout the world. While we believe there remains substantial data to support the role of hypoxia in cancer treatment resistance, we are deeply frustrated with our inability in these trials to impact that in a meaningful way. I would like to thank all of the patients and their families, and the physicians, nurses, and support staff who participated in these studies."

Conference Call and Webcast
At 8:30 a.m. Eastern Time on Monday December 7, 2015, Threshold’s management will host a conference call and a simultaneous webcast. The webcast can be accessed on the company’s website in the Investors/Webcasts section View Source Alternatively, please call 1- (888) 767-9745 (U.S) or (440) 996-5547 (international). The conference ID number is 99761325. The webcast will be archived on Threshold’s website for at least 30 days.

About TH-CR-406/SARC021
TH-CR-406/SARC021 is a randomized, open-label, global, multicenter Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (300 mg/m2) in combination with doxorubicin (75 mg/m2) compared with doxorubicin alone, in patients with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy. A total of 640 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include progression-free survival (PFS), response rate, safety and pharmacokinetics.

About MAESTRO
MAESTRO (MetAstatic or unrESectable pancreaTic adenocaRcinOma) is a randomized, placebo-controlled, international, multicenter, double-blind Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (340 mg/m2) in combination with gemcitabine (1000 mg/m2), compared with gemcitabine and placebo, in patients with previously untreated, locally advanced, unresectable or metastatic pancreatic adenocarcinoma. A total of 693 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include PFS, overall response rate, disease control rate, quality of life based on patient-reported outcomes, safety and tolerability, pharmacokinetics and biomarkers.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

Evofosfamide is being studied in patients with locally advanced unresectable or metastatic soft tissue sarcoma and in patients with locally advanced unresectable or metastatic pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 study designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical studies of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany.

On December 7, 2015 iTeos Therapeutics SA, the drug discovery company for immunomodulators,reported that it has received a €2.94 million non-dilutive funding from the Walloon Region of Belgium to expand its preclinical drug discovery pipeline targeting new immunotherapies for the tumor micro-environment (Press release, iTeos Therapeutics, DEC 7, 2015, View Source [SID:1234513306]).

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"This grant will allow us to expand our proprietary pipeline by adding a program to develop small molecule inhibitors for a target involved in T cell anergy". said Christophe Quéva Ph.D., chief scientific officer of iTeos. "It will complement our growing portfolio of small molecules and antibody approaches aimed at stimulating certain immune responses against cancers."

"We are very pleased to continue to receive strong support for our preclinical research from the Walloon Region. In parallel to our strategic collaboration with Pfizer, which was announced in 2014, we are expanding the Company’s drug candidate pipeline where such grant support is pivotal for our research efforts to discover our own diversified and innovative set of drug candidate programs." said Michel Detheux Ph.D., chief executive officer of iTeos.