On April 7, 2014 Cancer Research Technology (CRT), the commercial arm of Cancer Research UK announces a successful outcome to their existing collaboration with Teva through the identification of a novel atypical Protein Kinase C (aPKC) inhibitor pre-clinical candidate, licensed by Teva (Press release Cancer Research UK, APR 7, 2014, View Source [SID:1234500378]).
The successful multi-year, cross-discipline, collaboration between CRT and Teva has produced a first-in-class, highly selective and orally-active pre-clinical candidate inhibitor for development by Teva into possible new drug therapies for cancer patients.
The drug compound blocks the atypical class of Protein Kinase C (PKC) proteins that are differentially activated in defined subsets of cancer patients. The aPKC inhibitor pre-clinical candidate was discovered following lead optimisation of early stage compounds identified within the CRT Discovery Laboratories. Teva provided significant resource and expertise during the collaborative research term to boost existing investment by Cancer Research UK.
The aPKC isoforms PKC iota and PKC zeta are types of enzymes called serine/threonine kinases that have a key role in regulating the formation of tumours (tumourigenesis), the early steps of tumor invasion and metastasis (tumor spread) to distant tissues, and the expansion and growth of cancer stem cells, which contribute to the emergence of tumor resistance to a variety of standard cancer therapies. Inhibition of the aPKC isoenzymes is an attractive target for anti-tumour treatments. Professors Peter Parker and Neil McDonald, at Cancer Research UK’s London Research Institute, significantly contributed to understanding the structural biology of the aPKC drug targets and their validation as important players in cancer cell growth and spread.
Under the terms of the license, CRT receive an upfront payment, and will be eligible to receive future success-based development milestone payments and royalty payments upon reaching specified targets once the drug is marketed.

On April 7, 2014 Oncothyreon reported that Merck KGaA has initiated the international Phase 3 START2 study (NCT02049151), which is designed to assess the efficacy and safety of the investigational MUC1 antigen-specific cancer immunotherapy tecemotide (also known as L-BLP25) in patients with unresectable, locally advanced Stage III non-small cell lung cancer (NSCLC) (Press release Oncothyreon, APR 7, 2014, View Source [SID:1234500374]). Merck KGaA is developing tecemotide under a license agreement with Oncothyreon.
The START2 study is a Phase 3, multicenter, 1:1 randomized, double-blind, placebo-controlled clinical trial designed to assess the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced (Stage IIIA or IIIB) NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent chemoradiotherapy (CRT). Concurrent CRT – a combination of chemotherapy and radiotherapy given at the same time – is the current standard of care for most of these patients. The study is expected to recruit approximately 1,000 patients. The primary endpoint is overall survival (OS). Secondary endpoints include time to symptom progression, progression-free survival and time to progression. Merck KGaA, Darmstadt, Germany received Scientific Advice from the European Medicines Agency (EMA) on the program and reached an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the trial.
START2 is based on the outcome of the prior START trial. While the START trial did not meet the primary endpoint of improving OS in the overall patient population, data from an exploratory analysis of a predefined subgroup of patients, who received tecemotide after concurrent CRT, showed that these patients achieved a median OS of 30.8 months versus 20.6 months in patients treated with placebo (n=806; HR: 0.78; 95% CI 0.64-0.95; p=0.016).

On April 7, 2014 MEI Pharma reported the presentation of new pre-clinical data showing the ability of its lead drug candidate Pracinostat to inhibit bladder cancer cell growth and induce activated transcription factor 3 (ATF-3) expression, a potential marker of tumor response (Press release MEI Pharma, APR 7, 2014, View Source [SID:1234500372]). The data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego.
Previous studies have shown that decreased ATF-3 expression is associated with tumor progression and reduced rate of survival in patients with bladder cancer. This study, conducted in collaboration with the Centre for Cancer Research, MIMR-PHI Institute of Medical Research in Melbourne, Australia, demonstrated that ATF-3 expression is reactivated in bladder cancer cells treated with Pracinostat in vitro. In addition, the study showed that Pracinostat treatment induced reactivation of ATF-3 in xenograft tumor samples.
Poster is available here, View Source .

On April 7, 2014 Ambit Biosciences reported the initiation of the Phase 2 cohort of the MD Anderson Cancer Center-sponsored Phase 1/2 study of quizartinib in combination with either 5-azacitidine or low dose cytarabine for previously untreated FLT3-ITD positive acute myeloid leukemia (AML) patients age 60 or older, or FLT3-ITD positive AML patients 18 years of age or older in first relapse (Press release Ambit Biosciences, APR 7, 2014, View Source [SID:1234500370]).
The trial is being conducted under the principal direction of Jorge Cortes, M.D., of The University of Texas MD Anderson Cancer Center. Dr. Cortes is also the principal investigator of the upcoming Phase 3 QUANTUM-R trial, the Company’s randomized trial comparing quizartinib to standard chemotherapy in FLT3-ITD positive AML patients over the age of 18 who have relapsed from, or are refractory to, frontline chemotherapy, including those patients relapsing following a hematopoietic stem cell transplant (HSCT).
The Phase 2 cohort follows completion of the Phase 1 open-label, two-arm portion which included twelve total patients, six in each arm. Phase 1 included patients who were 18 years of age or older and who had relapsed AML or myelodysplastic syndrome (MDS) and were treated with quizartinib in combination with either 5-azacitidine or cytarabine. Up to a total of 64 patients are planned to be treated in this clinical trial. The regimen was found to be generally well tolerated, and there were no early mortalities. Despite limited follow up, evidence of anti-leukemia activity has been observed in a number of patients. Full results, including data from the Phase 2 cohort, are expected to be submitted to a medical conference in 2014.