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Kura Oncology Provides Update on Phase 2 Trial of Tipifarnib in HRAS Mutant Head and Neck Cancer

On February 15, 2018 Kura Oncology, Inc. (Nasdaq:KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the presentation of updated preliminary results from its Phase 2 clinical trial of its lead product candidate, tipifarnib, in patients with head and neck squamous cell carcinomas (HNSCC) with HRAS mutations (Press release, Kura Oncology, FEB 15, 2018, View Source [SID1234524150]).

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The results are being presented by Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center at the 2018 Multidisciplinary Head and Neck Cancers Symposium, taking place today in Scottsdale, Arizona. A copy of the poster is available online at www.kuraoncology.com.

Nine patients with HRAS mutant HNSCC had been enrolled in the Phase 2 trial as of the February 8, 2018 data cutoff date. Five out of the six evaluable patients achieved a confirmed, partial response as defined by standard RECIST criteria for an overall response rate of 83% (36-99.6%, 95%CI), including durable responses of more than 18 months in two patients. The sixth evaluable patient experienced tumor shrinkage and prolonged disease stabilization. Three additional patients were enrolled since the last update in October 2017, however, none of the three additional patients was evaluable as of the February 8th data cutoff date; two are off study and one was still too early for disease assessment.

"We continue to be very encouraged by the high level of clinical activity of tipifarnib observed in patients with HRAS mutant HNSCC," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "In addition to rapid responses in patients who do not appear to benefit from current standards-of-care, we are also seeing dramatic resolution of disfiguring and often painful lesions. We are continuing to enroll patients in the ongoing Phase 2 trial while we gather input from regulatory agencies on the design of a potential registrational trial of tipifarnib in HRAS mutant HNSCC anticipated to be initiated later this year."

All patients joined the trial upon progression from at least one line of therapy, including chemotherapy, cetuximab or immune therapy, with patients having experienced a median of two prior therapies (range, 1-4). Response rates for the three agents approved for treatment of HNSCC in the second line are in the range of 13-16%, with a median progression-free survival of approximately 2 months and a median overall survival of up to 7.5 months.

Tipifarnib was generally well-tolerated in the trial. Adverse events observed are consistent with the known safety profile of tipifarnib.

In September 2017, Kura announced that the Phase 2 trial in HRAS mutant HNSCC had achieved its primary efficacy endpoint prior to the completion of enrollment. The trial protocol required four confirmed, partial responses, per RECIST 1.1 criteria, out of 18 patients to meet its primary endpoint.

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is an inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown a well-established safety profile and compelling and durable anti-cancer activity in certain patient subsets. Preclinical and clinical data suggest that, in the appropriate context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura Oncology is seeking to identify patients most likely to benefit from tipifarnib. In addition to its development program in solid tumors with HRAS mutations, Kura has identified potential biomarkers of activity for tipifarnib in hematologic malignancies, including peripheral T-cell lymphomas (PTCL), myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML).

Selumetinib Granted Orphan Drug Designation by the U.S. FDA for Neurofibromatosis Type 1

On February 15, 2018 -AstraZeneca and Merck (NYSE:MRK), known as MSD outside the U.S. and Canada, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for selumetinib, a MEK 1/2 inhibitor, for the treatment of neurofibromatosis type 1 (NF1) (Press release, Merck & Co, FEB 15, 2018, View Source [SID1234524008]).

NF1 is an incurable genetic condition that affects one in 3,000 births with highly-variable symptoms including cutaneous (skin), neurological (nervous system) and orthopedic (skeletal) manifestations. NF1 can cause secondary complications including learning difficulties, visual impairment, pain, disfigurement, twisting and curvature of the spine, high blood pressure and epilepsy. Plexiform neurofibromas (PNs) are tumors that arise from nerve fascicles and tend to grow along the length of the nerve. PNs, a neurological manifestation of NF1,occur in approximately 20-50 percent of NF1 patients causing pain, motor dysfunction and disfigurement.

Sean Bohen, executive vice president, global medicines development and chief medical officer, AstraZeneca, said, "Neurofibromatosis type 1 is a devastating condition that can lead to life-threatening complications. There is no known cure for neurofibromatosis and there are limited treatment options to manage symptoms."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "This is an important collaborative effort with our colleagues at AstraZeneca addressing an area of significant unmet medical need to potentially benefit patients with neurofibromatosis type 1."

The potential benefit of selumetinib in NF1 is being explored in the U.S. National Cancer Institute-sponsored phase 1/2 SPRINT trial in pediatric patients with symptomatic NF1-related PNs. Phase II trial results are expected later in 2018.

The FDA’s ODD program provides orphan status to medicines that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S.

In addition to NF1, selumetinib is being investigated in the phase 3 ASTRA trial of patients who are diagnosed with differentiated thyroid cancer (DTC) following surgery and treatment with radioactive iodine. Selumetinib was granted ODD by the US FDA for the adjuvant treatment of stage 3/4 DTC in 2016. It is also being explored as a monotherapy and in combination with other treatments in phase 1 trials.

NOTES TO EDITORS

About neurofibromatosis type 1 (NF1)

The NF1 gene provides instructions for making a protein called Neurofibromin. The disease is associated with many symptoms, including soft lumps on and under the skin (subcutaneous neurofibromas), skin pigmentation (cafe au lait spots) and, in 20-50 percent of patients, tumors on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause morbidities such as pain, motor dysfunction and disfigurement. Patients with NF1 may experience a number of other complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. People with NF1 also have an increased risk of developing other cancers, including malignant brain and peripheral nerve sheath tumors, and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.

About selumetinib

Selumetinib, is an investigational MEK 1/2 inhibitor licensed by AstraZeneca from Array BioPharma Inc. in 2003.

The NF1 gene codes for a protein called Neurofibromin. This protein negatively regulates the RAS/MAPK pathway, which helps to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulation in RAS/RAF/MEK/ERK signaling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumor growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumor growth.

Roche to acquire Flatiron Health to accelerate industry-wide development and delivery of breakthrough medicines for patients with cancer

On February 15, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) and Flatiron Health, Inc. reported that the two partners have signed a definitive agreement under which Roche will acquire all shares of Flatiron Health, following on from an existing equity stake of 12.6% (Press release, Hoffmann-La Roche, FEB 15, 2018, View Source [SID1234524003]). The transaction is expected to close in the first half of 2018.

Flatiron Health, a privately held healthcare technology and services company headquartered in New York City, US, is a market leader in oncology-specific electronic health record (EHR) software, as well as the curation and development of real-world evidence for cancer research. With its large network of community oncology practices and academic medical centers across the US, Flatiron Health has created a technology platform designed to learn from the experience of every patient.

Daniel O’Day, CEO Roche Pharmaceuticals said, "This is an important step in our personalised healthcare strategy for Roche, as we believe that regulatory-grade real-world evidence is a key ingredient to accelerate the development of, and access to, new cancer treatments. As a leading technology company in oncology, Flatiron Health is best positioned to provide the technology and data analytics infrastructure needed not only for Roche, but for oncology research and development efforts across the entire industry. A key principle of this is to preserve Flatiron’s autonomy and their ability to continue providing their services to all existing and future partners."

Flatiron Health has worked with industry leaders and regulators to develop new approaches for how real-world evidence may be used in regulatory decision making, including the design and validation of novel endpoints. By working closely with its network of community practices and academic medical centers, Flatiron has also developed a suite of software products that uniquely positions the company to advance the use of real-world evidence at the point of care.

Nat Turner, Flatiron Health Co-Founder and CEO said, "Roche has been a tremendous partner to us over the past two years and shares our vision for building a learning healthcare platform in oncology ultimately designed to improve the lives of cancer patients. This important milestone will allow us to increase our investments in our provider-facing technology and services platform, as well as our evidence-generation platform, which will remain available to the entire healthcare industry."

Under the terms of the agreement, Roche will make a payment of USD 1.9 billion to Flatiron Health on a fully diluted basis, subject to certain adjustments. The closing of the transaction is subject to customary closing conditions. The parties expect that following the closing, Flatiron Health will continue its current business model, network of partnerships and overall objectives. The integrity of segregated patient protected health information will be preserved, as will dedicated sales and marketing, provider-facing and life science business activities.

JAMA Oncology Publication Demonstrates EndoPredict® (EPClin) Significantly Outperforms Oncotype DX® Recurrence Score in Early-Stage Breast Cancer

On February 15, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN) reported that a comparative analysis of commercially available prognostic breast cancer tests in patients with early-stage breast cancer has been published in JAMA Oncology (Press release, Myriad Genetics, FEB 15, 2018, View Source [SID1234524010]). A key finding is that Myriad’s EndoPredict (EPClin) significantly outperformed Oncotype DX Recurrence Score at predicting the risk of disease recurrence in patients with early-stage breast cancer.

In the article, Sestak et al. compared the prognostic value that four different commercial tests add to the Clinical Treatment Score (nodal status, tumor size, grate, age, endocrine treatment) for predicting distant recurrence (0-10 years) and late-distant recurrence (5-10 years) of breast cancer. The analysis included data from 774 postmenopausal women with ER+/HER2- breast cancer with node-negative disease or up to three positive lymph nodes, which is the most common form of breast cancer.

The results show that in all patients EndoPredict was the best overall test in predicting distant recurrence in years 0-10 (C-index 0.753; LRX2=69.3) and years 5-10 (C-index 0.761; LRX2=41.6). Importantly, EndoPredict identified the largest group of low-risk patients with 10 years distant recurrence below 10 percent in both node-negative and node-positive disease. EndoPredict also was a much better predictor for overall distant recurrence and for late-distant recurrence than Oncotype DX Recurrence Score. The JAMA Oncology publication can be accessed at View Source

"This study demonstrates that EndoPredict, which combines a multigene signature with clinical information, significantly improves the prediction of disease recurrence, specifically in women with node-positive breast cancer," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetics. "What this means is that EndoPredict can more accurately identify a larger percentage of patients who can safely forgo adjuvant chemotherapy and the associated toxicity."

These findings are consistent with a previous publication in the Journal of the National Cancer Institute, which also found that EndoPredict was superior to Oncotype DX Breast Recurrence Score in predicting the long-term recurrence of ER+, HER2- primary breast cancer.

Additionally, at the 2017 San Antonio Breast Cancer Symposium in December, the Company presented new predictive data that demonstrated women with a high EndoPredict score responded better to neoadjuvant chemotherapy than those with a low score, while those with a low score responded better to neoadjuvant endocrine therapy.

"We are committed to saving and improving the lives of women with breast cancer, and making sure patients are benefitting from the latest advances in personalized medicine," said Lancaster. "Our expanding body of evidence strongly supports the use of EndoPredict to aid in clinical decisions regarding the use of chemotherapy and extended endocrine therapy."

EndoPredict is widely accessible and is covered by more than 90 percent of health insurance plans in the United States. It also is available in several major European markets. For more information, please visit: www.endopredict.com.

Follow Myriad on Twitter via @MyriadGenetics to stay informed about news and updates from the Company.

Medical Policy Update
One of the largest private insurers in the United States has expanded its coverage policy on EndoPredict. The new policy supports the use of EndoPredict to aid in the controversial decision of whether or not to extend adjuvant hormonal therapy beyond five years of treatment.

"I applaud payers for recognizing the importance of biomarkers to help physicians and patients make important decisions about whether or not to use extended endocrine therapy out to 10 years," said Joyce A. O’Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research, Baylor University Medical Center, and Chair of Breast Cancer Research at Texas Oncology. "This is another important step toward making personalized medicine a reality for all patients with breast cancer."

About Breast Cancer

One in eight American women will have breast cancer during her lifetime. Breast cancer is the second leading cause of cancer death among American women. The American Cancer Society estimates in its Cancer Facts & Figures 2018 report that more than 250,000 women will be told they have breast cancer in 2018. Currently, there are nearly 3.5 million American women living with the disease and every 13 minutes another American woman dies from breast cancer. That’s a little more than 40,000 this year.

About EndoPredict

EndoPredict is a second-generation, multigene prognostic test that aids personalized treatment planning for patients with early stage breast cancer. EndoPredict has been validated in approximately 4,000 patients with node-negative and node-positive disease and has been used clinically in more than 20,000 patients. In contrast to first-generation multigene prognostic tests, EndoPredict accurately predicts the likelihood of both early (0-5 years) and late distant recurrence (5-10 years). Thus, EndoPredict can guide treatment decisions on both the need for chemotherapy, as well as extended endocrine therapy. For more information, please visit: www.endopredict.com.

Moleculin Announces Breakthrough Discovery of a New Molecule for Cancer Treatment

On February 15, 2018 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the MD Anderson Cancer Center ("MD Anderson"), reported that, pursuant to its continued collaboration with MD Anderson it has developed and licensed what it believes, based on preclinical testing, is a major breakthrough in its effort to develop a new cancer treatment that selectively kills highly resistant tumors (Press release, Moleculin, FEB 15, 2018, View Source [SID1234524009]).

"We believe our unique approach to develop immuno-stimulating STAT3 inhibitors just took a major step forward," commented Walter Klemp, Chairman and CEO of Moleculin. "Our WP1066 portfolio has already resulted in multiple collaborations with some of the most prestigious cancer centers in the world and now this new discovery could dramatically improve our ability to treat a broader range of the most difficult cancers, and especially pancreatic cancer."

Dr. Don Picker, Moleculin’s Chief Science Officer, explained, "The scientific community recognizes the potential for small molecule immuno-stimulating STAT3 inhibitors to become a game-changer for treating cancer patients. We believe this discovery may not only dramatically improve our ability to develop and deliver such therapies, it may also help support a new mechanistic understanding of oncogenic transcriptional activity. Specifically, we now have preclinical evidence to suggest we are capable of controlling a process known as ‘ubiquitination’ to block the activated form of STAT3, an important oncogenic transcription factor. The study of the role of ubiquitination in cancer is cutting edge science and appears to hold great promise. And, given the desperate lack of treatment options for indications like pancreatic cancer, we believe clinical researchers across the country have been eagerly awaiting a breakthrough like this."

"In developing our current lead STAT3 inhibitor, WP1066, for brain tumors, we have focused on its oral bioavailability and brain uptake," continued Dr. Picker, "but at the same time we have continued our quest to expand this portfolio by the creating alternative inhibitors with increased bioavailability and altered tissue and organ distribution that are not affected by first-pass metabolism. The lead molecule resulting from this new discovery is called WP1732 and it not only appears to share the same key mechanistic properties with WP1066, it has markedly different organ distribution and its dramatically increased solubility makes it ideal for administration via standard IV injection. Importantly, preclinical testing has also shown that WP1732’s properties make it a promising candidate for treating pancreatic cancer, one of the most resistant and deadly forms of cancer."

"So much has happened in the past few months, it’s important to recap where we are," added Mr. Klemp. "Moleculin has three potential breakthrough disruptive technologies – (1) Annamycin, an anticancer agent that is active against multidrug resistant tumor cells and has been designed to be non-cardio toxic (unlike currently approved drugs in this class), (2) immuno-stimulating STAT3 inhibitors like WP1066 and, now, WP1732, and (3) WP1122, a metabolic inhibitor that has been shown in preclinical testing to effectively block the energy supply required by cancer cells to function and proliferate. Since our IPO in June 2016, we have accelerated to the point of having two drugs, Annamycin and WP1066, beginning clinical trials in the near term."

Mr. Klemp concluded, "We are now demonstrating the breadth of our drug pipeline and the benefits of collaborating with world-class cancer research centers. In the AML space, we expect patient dosing either in the United States or Poland to begin with Annamycin yet this quarter and we have begun to work with researchers at MD Anderson on using our immuno-stimulating STAT3 inhibitors to target AML as well. A second clinical trial targeting brain tumors with WP1066 should begin dosing within the first half of the year. In Poland, we are about to request a clinical trial authorization for WP1220 for the topical treatment of Cutaneous T-Cell Lymphoma (CTCL), which we expect will become our third clinical trial this year. WP1220 is our patented STAT3 inhibitor designed to be compatible with topical formulations and was selected based on its preclinical activity in CTCL cell lines and based on the need for better topical treatments for CTCL. Additionally, we just announced positive data for WP1122, our glycolysis inhibitor, in a pancreatic cancer mouse model. Along with the newly licensed discovery of WP1732, this sets the course for establishing the base for two more Investigational New Drug (IND) applications over the coming year and positions us as a leader in developing new approaches for pancreatic cancer. Our highly experienced leadership and expanding team is looking forward to sharing more progress on all of this activity as we move forward into 2018."