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Exelixis Announces Positive Overall Survival Results from Phase 3 Pivotal Trial of Cobimetinib in Combination with Vemurafenib in Patients with BRAF V600 Mutation-Positive Advanced Melanoma

On October 6, 2015 Exelixis, Inc. (NASDAQ:EXEL) reported positive overall survival (OS) results from coBRIM, the phase 3 pivotal trial evaluating cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma carrying a BRAF V600 mutation (Press release, Exelixis, OCT 6, 2015, View Source [SID:1234507644]).

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Exelixis’ collaborator Genentech, a member of the Roche Group, informed the company that coBRIM met its secondary endpoint of demonstrating a statistically significant and clinically meaningful increase in overall survival for patients receiving the combination of cobimetinib and vemurafenib, as compared to vemurafenib monotherapy. Ongoing study monitoring did not identify any new safety signals. Long-term safety data are expected later this year. These data will be the subject of a presentation at an upcoming medical meeting.

"The positive effect of the combination of cobimetinib and vemurafenib on overall survival is a major step forward for patients with advanced BRAF V600 mutation-positive melanoma in search of new treatment options," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We continue to work with our partners at Genentech in preparation for the potential U.S. approval and launch of cobimetinib to deliver this important potential treatment option to patients, physicians and caregivers in the United States as quickly as possible."

Exelixis announced the first regulatory approval of cobimetinib in Switzerland in August 2015. U.S. and EU regulatory applications sponsored by Genentech and Roche, respectively, are currently under review. In the United States, the Prescription Drug User Fee Act action date is November 11, 2015. In the EU, Roche anticipates a regulatory decision by the end of this year following a positive opinion from the European Committee for Medicinal Products for Human Use announced in late September.

About the coBRIM Study

The coBRIM trial is an international, randomized, double-blind, placebo-controlled Phase III study evaluating the safety and efficacy of 60 mg once daily of cobimetinib in combination with 960 mg twice daily of vemurafenib, compared to 960 mg twice daily of vemurafenib alone. In the study, 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma (detected by the cobas 4800 BRAF Mutation Test) and previously untreated for advanced disease, were randomized to receive vemurafenib every day on a 28-day cycle plus either cobimetinib or placebo for days 1-21. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent. Investigator-assessed PFS is the primary endpoint. Secondary endpoints include PFS by independent review committee, overall response rate, overall survival, duration of response and other safety, pharmacokinetic and quality of life measures.

About the Cobimetinib Development Collaboration

Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the end of phase 1, at which point Genentech exercised its option to further develop the compound.

If cobimetinib is approved in the United States, Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share in U.S. marketing and commercialization costs. In November 2013, Exelixis exercised its option to co-promote cobimetinib in the United States and, under the terms of the agreement, the company is prepared to field up to 25 percent of the U.S. sales force.

About the Combination of Cobimetinib and Vemurafenib

Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK pathway) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50 percent of tumors. About 50 percent of patients with BRAF mutation positive melanoma experience a tumor response when treated with a BRAF inhibitor, however development of resistance and subsequent tumor progression limits treatment benefit. Clinical and preclinical analyses indicated that reactivation of the MEK-ERK pathway may underlie development of resistance to BRAF inhibitors in many progressing tumors, and that co-treatment with a BRAF and MEK inhibitor delays the emergence of resistance in the preclinical setting, providing the rationale for testing the combination of vemurafenib and cobimetinib in clinical trials. In addition to the combination with vemurafenib in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.

About Melanoma and its BRAF V600 Mutation-Positive Form

Melanoma is the less common, but more serious category of skin cancer that starts in the skin’s pigment producing cells known as melanocytes. According to the American Cancer Society, approximately five percent of skin cancer diagnoses are melanoma, but melanoma accounts for a large majority of skin cancer deaths. In recent years, there have been significant advances in treatment for metastatic melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years. It is projected that approximately half of all melanomas, and eight percent of solid tumors, contain a mutation of the BRAF protein. BRAF is a key component of the RAS-RAF-MEK-ERK pathway involved in normal cell growth and survival. However, mutations that keep the BRAF protein in an active state may cause excessive signaling in the pathway, leading to uncontrolled cell growth and survival. The BRAF V600 mutation-positive form of melanoma is associated with high-risk characteristics of the disease, including early onset, the absence of chronic skin damage, and decreased survival.

FDA approves expanded indication for medical device to treat a form of brain cancer

On October 5, 2015 The U.S. Food and Drug Administration reported they approved an expanded indication for the Optune device to treat patients with newly-diagnosed glioblastoma multiforme (GBM), an aggressive form of brain cancer (Press release, , OCT 5, 2015, View Source [SID:1234507650]). It is given along with the chemotherapy drug temozolomide (TMZ) following standard treatments that include surgery, chemotherapy, and radiation therapy.

Nearly 23,000 Americans will be diagnosed with brain or other nervous system cancers in 2015, according to the National Cancer Institute, and more than 15,000 will die from them. GBM accounts for about 15 percent of all brain tumors, and typically occurs in adults ages 45 to 70. Patients survive less than 15 months on average following diagnosis, because the tumor tends to be highly resistant to standard treatments.

"Patients newly diagnosed with this challenging and aggressive form of brain cancer now have another treatment option available," said William Maisel, M.D., M.P.H., acting director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. "While the treatment is not a cure, it can increase survival by several months."

In the clinical study used to support the expanded indication, patients treated with the device and TMZ lived on average three months longer than those treated with the drug alone.

Optune was initially approved in 2011 to treat patients with GBM that recurred or progressed after chemotherapy. With this expanded indication, Optune can be used as part of a standard treatment for GBM before the disease progresses.

For newly diagnosed GBM, Optune is not intended to be used as a substitute for standard treatments, but rather as an adjunct therapy, and should not be used without a physician’s supervision.

When using Optune, a health care professional places electrodes on the surface of the patient’s scalp to deliver low-intensity, alternating electrical fields called "tumor treatment fields" (TTFields). The unique shape and special characteristics of rapidly dividing tumor cells make them susceptible to damage when exposed to TTFields, which could halt tumor growth.

The device is portable and can be powered with batteries or plugged into an electrical outlet. Patients can use the device at home or work, allowing them to continue their normal daily activities.

The FDA based its approval of the expanded indication of the Optune device on results from a clinical trial involving 695 patients newly diagnosed with GBM that compared those who used Optune with TMZ to those receiving TMZ alone. Patients who used the device along with TMZ lived, on average, about seven months with no disease progression compared to four months for those who had the drug alone. The Optune plus TMZ group survived for an average of 19.4 months after diagnosis compared to 16.6 months for those who were treated with only TMZ.

Optune for newly diagnosed GBM was reviewed under the FDA’s priority review program, which provides for an expedited review of certain devices that treat life-threatening conditions.

The most common side effect experienced with Optune was skin irritation. Clinical trial participants also experienced a slightly higher incidence of neurological side effects, including convulsions and headaches, compared to subjects receiving TMZ alone.

Patients should not use the Optune system if they have an active implanted medical device or a skull defect, have an underlying skin condition involving the scalp or have a known sensitivity to conductive hydrogels, such as those used on electrocardiogram stickers.

The Optune System is made by Novocure Inc. of Portsmouth, New Hampshire.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Myriad to Present Seven Studies at the ASHG Annual Meeting

On October 5, 2015 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that there will be seven poster presentations featured at American Society for Human Genetics (ASHG) meeting being held Oct. 6 to 10, 2015 in Baltimore, Md (Press release, Myriad Genetics, OCT 5, 2015, View Source [SID:1234507643]).

"At Myriad, we are passionately committed to providing the most accurate hereditary cancer tests through extensively validated laboratory and variant interpretation processes. We have spent almost two decades of research to provide the most sophisticated and comprehensive variant classification program," said Rick Wenstrup, M.D., chief medical officer, Myriad Genetics. "We look forward to presenting these seven new studies at ASH (Free ASH Whitepaper)G as we continue to advance the state-of-the-art in variant classification with innovative new approaches."

A list of the Myriad presentations at ASH (Free ASH Whitepaper)G (#ASHG15) follows:

Poster Presentations

Title: RNA functional studies for the classification of germline variants of uncertain significance that may impair splicing.
Date: Wednesday, Oct. 7, 2015: 5:00 to 6:00 p.m. ET.
Location: Poster 2639W.

Title: No evidence for a difference in the severity of cancer history for carriers of missense versus truncating pathogenic variants in ATM.
Date: Thursday, Oct. 8, 2015: 12:00 to 1:00 p.m. ET.
Location: Poster 2750T.

Title: Detection of large rearrangements in a pan-cancer gene panel using next generation sequencing.
Date: Thursday, Oct. 8, 2015: 12:00 to 1:00 p.m. ET.
Location: Poster 2018T.

Title: Comparison of a literature search algorithm and curated publication database with the literature content of other locus specific databases.
Date: Thursday, Oct. 8, 2015: 12:00 to 1:00 p.m. ET.
Location: Poster 1739T.

Title: Analytical validation of a saliva collection and DNA extraction protocol increases accessibility to hereditary pan-cancer panel testing.
Date: Thursday, Oct. 8, 2015: 12:00 to 1:00 p.m. ET.
Location: Poster 1985T.

Title: Identification of retrotransposon insertion mutations in hereditary cancer.
Date: Thursday, Oct. 8, 2015: 12:00 to 1:00 p.m. ET.
Location: Poster 2592T.

Title: Does this patient need to be tested for Lynch Syndrome? Assessing the reliability of family history for ascertainment.
Date: Friday, Oct. 9, 2015: 11:45 a.m. to 12:45 p.m. ET.
Location: Poster 2082F.
For more information about these presentations, including a complete list of abstracts and posters, please visit the ASH (Free ASH Whitepaper)G website at www.ashg.org/2015meeting/pages/online-planner.shtml.

Argos Therapeutics to Host Review of the Current Clinical Research Landscape in Kidney Cancer Following the 40th Congress of the European Society for Medical Oncology, With Insights From Dr. Charles Drake of Johns Hopkins Sidney Kimmel Cancer Center

On October 5, 2015 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of fully individualized immunotherapies based on the Arcelis technology platform, reported the company will host a special briefing conference call focused on the current clinical research landscape in metastatic renal cell carcinoma (mRCC) (Press release, Argos Therapeutics, OCT 5, 2015, View Source [SID:1234507642]). The briefing will feature Dr. Charles Drake, co-director of the division of immunology, professor of medical oncology, immunology, and urology at the Johns Hopkins Sidney Kimmel Cancer Center. The conference call is scheduled for Wednesday, October 7, 2015 at 4:30pm ET.

During the briefing, Dr. Drake will review data presented during the 40th Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) held September 25-29, 2015 in Vienna, Austria, and will discuss the implications for clinical research in mRCC moving forward.

In addition to the presentation by Dr. Drake, Dr. Charles Nicolette, Argos’ chief scientific officer and vice president of research and development, will also provide an update on the company’s lead product candidate, AGS-003, and the pivotal ADAPT phase 3 clinical trial for the treatment of mRCC.

To participate by telephone, please dial (855) 433-0930 (Domestic) or (484) 756-4271 (International). The conference ID number is 55129797. A live and archived audio webcast can be accessed through the Investors section of the Company’s website at www.argostherapeutics.com. The archived webcast will remain available on the Company’s website for fourteen (14) days following the call.

About the Arcelis Technology Platform

Arcelis is a fully individualized immunotherapy technology that captures mutated and variant antigens that are specific to each patient’s disease. It is designed to overcome immunosuppression by producing a durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to a wide range of different cancers, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized cancer immunotherapies. The Arcelis process uses only a small tumor or blood sample and the patient’s own dendritic cells, which are optimized from cells collected by a single leukapheresis procedure. The proprietary process isolates RNA from the patient’s disease sample to program the optimized dendritic cells to present disease specific antigens to circulating T-cells in vivo. The antigen-loaded dendritic cells are also activated with CD40L, a critical co-stimulatory factor, then combined with the patient’s plasma and administered via intradermal injection, resulting in the activation, differentiation and proliferation of memory and tumor-specific killer T-cells. The high-yield process enables multiple doses to be created from a single patient cell collection.

ERGOMED INCREASES ITS CO-DEVELOPMENT CONTRIBUTION UP TO $12,000,000 IN CEL-SCI’S PHASE 3 HEAD AND NECK CANCER TRIAL

On October 5, 2015 CEL-SCI Corporation (NYSE MKT: CVM) ("CEL SCI" or the "Company") and its Clinical Research Organization (CRO) Ergomed plc (AIM: ERGO) reported that they have expanded their co-development agreement with increased activities to be undertaken by Ergomed (Press release, Cel-Sci, OCT 5, 2015, View Source [SID:1234507641]). Pursuant to the expanded co-development agreement, Ergomed’s contribution to the Phase 3 study will increase from $10,000,000 to $12,000,000. The companies are undertaking the Phase 3 trial of CEL-SCI’s investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary head and neck cancer.

Under the extended agreement, Ergomed will contribute up to $12,000,000 towards the cost of performing clinical services for the Phase 3 study in exchange for a single digit percentage of milestone and royalty payments, up to a specified maximum amount. Well over 500 patients have been enrolled in the world’s largest Phase 3 trial for head and neck cancer.

Ergomed CEO Miroslav Reljanovic stated, "At this point in the clinical trial we have decided to increase our investment in the development of Multikine, as we believe that it holds the potential to treat head and neck cancer in a new way. Our potential returns from this agreement will increase in line with our investment."

CEL-SCI CEO Geert Kersten added, "Working with a skilled CRO, our Phase 3 trial is making significant progress towards completing study enrollment goals. We are pleased to enter into this expanded co-development agreement with Ergomed. It further aligns Ergomed’s goals with CEL-SCI’s as Ergomed will be rewarded for its $12,000,000 co-development investment from the commercialization of the drug."

About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling patients with advanced primary squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, and at the University of California, San Francisco (UCSF), as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. Dr. Joel Palefsky, a world renowned scientist and Key Opinion Leader (KOL) in human papilloma virus (HPV) research and the prevention of anal cancer, is the Principal Investigator at UCSF, which was added to the study in July 2015.