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Bristol-Myers Squibb’s Opdivo (nivolumab) Receives Expanded FDA Approval in Previously-Treated Metastatic Non-Small Cell Lung Cancer (NSCLC), Offering Improved Survival to More Patients

On October 09, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported that the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection, for intravenous use, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (Press release, Bristol-Myers Squibb, OCT 9, 2015, View Source [SID:1234507686]).

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Patients with EGFR mutation or ALK translocation should have disease progression on appropriate targeted therapy prior to receiving Opdivo. In a Phase 3 trial, CheckMate -057, Opdivo demonstrated superior overall survival (OS) in previously treated metastatic non-squamous NSCLC compared to chemotherapy, with a 27% reduction in the risk of death (hazard ratio: 0.73 [95% CI: 0.60, 0.89; p=0.0015]), based on a prespecified interim analysis.1 The median OS was 12.2 months in the Opdivo arm (95% CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95% CI: 8.0, 10.7).1 This approval expands Opdivo’s indication for previously treated metastatic squamous NSCLC to include the non-squamous patient population. Squamous and non-squamous NSCLC together represent approximately 85% to 90% of lung cancer cases.2

Opdivo is associated with immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; and embryofetal toxicity.1 Please see the Important Safety Information section below.

"Improving survival for cancer patients represents the ultimate goal of treatment," said Murdo Gordon, senior vice president and head of Worldwide Markets, Bristol-Myers Squibb. "With today’s FDA approval, it is encouraging to know that Opdivo will be available to significantly more patients with metastatic NSCLC, helping to improve treatment outcomes for patients who have been previously treated. We hope that our efforts to bring innovative Immuno-Oncology treatments forward for patients will help increase survivorship and positively impact the lung cancer community."

This approval is the third for Opdivo in the United States this year, and is based on the results of the CheckMate -057 trial, a Phase 3 trial which demonstrated superior OS benefit for Opdivo vs. docetaxel in previously treated metastatic NSCLC. Opdivo is the only PD-1 therapy to have been studied in a Phase 3 trial of patients with previously treated squamous NSCLC and a separate Phase 3 trial of patients with previously treated non-squamous NSCLC. Biomarker testing is not required for Opdivo.

"Non-small cell lung cancer is a difficult to treat disease with high mortality, and patients with squamous and non-squamous NSCLC often respond differently to treatment," said Dr. Roy Herbst, Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. "Opdivo is becoming an important treatment option for more patients with previously treated metastatic NSCLC, and is a welcome addition to our therapy of this disease."

Proven Superior Overall Survival Versus Docetaxel in Metastatic NSCLC

CheckMate -057 is a landmark, comparative study designed with the goal of demonstrating survival. Clinical results from CheckMate -057 were recently presented at the 2015 European Cancer Congress with simultaneous publication in the New England Journal of Medicine. CheckMate -057 is a Phase 3, open-label, randomized clinical trial that evaluated Opdivo (3 mg/kg administered intravenously every two weeks) (n=292) vs. docetaxel (75 mg/m2 administered intravenously every three weeks) (n=290), in patients with metastatic non-squamous NSCLC who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen. Appropriate targeted therapy may have been given to patients with known EGFR mutation or ALK translocation.1 This study included patients regardless of their PD-L1 (programmed death ligand-1) expression status. The primary endpoint of this trial was OS.1

The median OS was 12.2 months in the Opdivo arm (95% CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95% CI: 8.0, 10.7).1 The hazard ratio (HR) was 0.73 (95% CI: 0.60, 0.89; p=0.0015), which translates to a 27% reduction in the risk of death with Opdivo compared to docetaxel.1 The prespecified interim analysis was conducted when 413 events were observed (93% of the planned number of events for final analysis).1 Additional secondary endpoints include investigator-assessed objective response rate (ORR) and progression-free survival (PFS). The ORR in the Opdivo arm was 19% (56/292; 4 complete responses, 52 partial responses) (95% CI: 15, 24) and 12% with docetaxel (36/290; 1 complete response, 35 partial responses) (95% CI: 9, 17) p=0.02. The median duration of response was 17 months in the Opdivo arm and 6 months in the docetaxel arm. Median PFS was 2.3 months in the Opdivo arm vs. 4.2 months with docetaxel; HR=0.92 (95% CI:0.77, 1.11, p=0.39).

"With today’s announcement, Opdivo represents the only PD-1 inhibitor approved for patients regardless of PD-L1 expression, and offers significant improvement over the current standard chemotherapy," said Michael Giordano, senior vice president, head of Development, Oncology, Bristol-Myers Squibb. "Through our leadership in Immuno-Oncology research, we have taken a comprehensive approach to better understanding and treating metastatic NSCLC, with a primary focus on patients who are in need of new options. We are committed to building upon the promise that Opdivo has demonstrated for patients and providing a potential survival benefit in devastating diseases, like metastatic NSCLC."

The safety profile of Opdivo in CheckMate -057 was consistent with prior studies. Serious adverse reactions occurred in 47% of patients receiving Opdivo. The most frequent serious adverse reactions in at least 2% of patients receiving Opdivo were pneumonia, pulmonary embolism, dyspnea, pleural effusions and respiratory failure. Opdivo was discontinued in 13% of patients and was delayed in 29% of patients for an adverse reaction. The most common adverse reactions (reported in ≥20% of patients) were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%) and constipation (23%).1

"The approval of Opdivo for patients with previously treated metastatic NSCLC represents a major advancement in the way we are able to address the unmet needs of these patients, especially for those who have progressed on prior treatment and, until now, may have had limited options," said Andrea Ferris, president and chairman of LUNGevity Foundation. "Bristol-Myers Squibb has shown unwavering commitment to improving survival expectations for patients with metastatic NSCLC and I applaud their work, along with the FDA, in making this treatment option available to more patients."

Bristol-Myers Squibb has partnered with Dako, an Agilent Technologies company, to develop PD-L1 IHC 28-8 PharmDx, a test which was used to assess PD-L1 expression in the CheckMate -057 trial. This test is now approved by the FDA as a complementary diagnostic, which will provide additional information for physicians. These tests are distinct from companion diagnostics, which are essential for safe and effective use of a drug. Biomarker testing is not required for Opdivo.

About Lung Cancer

Lung cancer is one of the leading causes of cancer deaths in the United States.2 NSCLC is one of the most common types of the disease and accounts for approximately 85% to 90% of lung cancer cases.2 Squamous NSCLC accounts for approximately 25% to 30% of all lung cancer cases, while non-squamous NSCLC accounts for approximately 45% to 60% of all lung cancer cases.2 Survival rates vary depending on the stage and type of the cancer and when it is diagnosed. For Stage IV NSCLC, the five-year survival rate is one percent.2

Tokai Pharmaceuticals Announces Presentation of AR-V7 Clinical Trial Assay at the Prostate Cancer Foundation’s Annual Scientific Retreat

On October 8, 2015 Tokai Pharmaceuticals, Inc. (NASDAQ: TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally-driven diseases, reported that a detailed overview of its AR-V7 clinical trial assay will be presented tonight at a poster session during the 22nd Annual Prostate Cancer Foundation Scientific Retreat in Washington, DC (Press release, Tokai Pharmaceuticals, OCT 8, 2015, View Source;p=RssLanding&cat=news&id=2095723 [SID:1234507683]).

The AR-V7 clinical trial assay reliably detects both full-length androgen receptor (AR) and the AR-V7 splice variant under a variety of conditions in AR-positive circulating tumor cells of men with treatment-naïve metastatic castration resistant prostate cancer (mCRPC). The AR-V7 splice variant, a truncated form of the AR, has been associated with non-response to commonly-used oral therapies for mCRPC. The assay is currently being used to screen patients for eligibility to participate in ARMOR3-SV, Tokai’s pivotal trial designed to evaluate whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to Xtandi (enzalutamide) in 148 treatment-naïve, AR-V7+ mCRPC patients. Topline results from ARMOR3-SV are anticipated by the end of 2016.

"We believe there is a significant unmet medical need for patients with AR-V7 positive metastatic castration resistant prostate cancer," said Karen J. Ferrante, M.D., Chief Medical Officer and Head of Research and Development of Tokai. "Given the Prostate Cancer Foundation’s mission to accelerate research and heighten awareness of the disease, we are pleased to present our assay at its annual meeting. The assay is a critical component of our ARMOR3-SV trial, which is the first pivotal study in prostate cancer trial to employ a precision medicine approach for patient selection."

A copy of the presentation will be available on the publications page of Tokai’s website, www.tokaipharma.com.

Onconova Therapeutics Announces $16.5M Share Purchase Agreement With Lincoln Park Capital Fund

On October 08, 2015 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported that the Company has entered into a share purchase agreement and a registration rights agreement ("Agreements") with Lincoln Park Capital Fund, LLC ("LPC") (Press release, Onconova, OCT 8, 2015, View Source [SID:1234507682]). Upon signing the Agreements, LPC made an initial purchase of 846,755 shares of the Company’s common stock for $1,500,000. Under the terms and subject to the conditions of the Agreements, the Company has the right to sell to, and LPC is obligated to purchase, up to an additional $15,000,000 in amounts of shares of the Company’s common stock, subject to certain limitations, from time to time, over the 36-month period commencing on the date that a registration statement, which the Company agreed to file with the Securities and Exchange Commission, is declared effective and a final prospectus is filed. In consideration for entering into the Agreements, Onconova has issued common shares to LPC as a commitment fee.

LPC cannot require any sales by the Company, but is obligated to make purchases from Onconova as the Company directs. Onconova has the right to terminate the Agreements at any time, at no cost or penalty. LPC has covenanted not to cause or engage in any manner whatsoever, any direct or indirect short selling or hedging of the Company’s common stock.

The Company expects that any net proceeds received from this offering will be used to support the clinical development of rigosertib, as well as for general corporate purposes and working capital requirements.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any shares of common stock, nor shall there be any sale of shares of common stock in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

EISAI RECEIVES APPROVAL FOR ANTICANCER AGENT LENVIMA(R) IN SOUTH KOREA

On October 9, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has received marketing approval of its novel in-house developed anticancer agent Lenvima (lenvatinib mesylate) as a treatment for patients with progressive, locally recurrent or metastatic, differentiated thyroid carcinoma (DTC), refractory to radioactive iodine (RAI) from the regulatory authority in South Korea (Ministry of Food and Drug Safety) (Press release, Eisai, OCT 8, 2015, View Source [SID:1234507678]). The marketing authorization application for Lenvima in South Korea was submitted in November 2014, and through the approval of this application, South Korea is the first country in Asia where Lenvima has been approved following Japan, the United States and Europe.

The decision to approve Lenvima in South Korea was based on the results of a pivotal Phase III study (the SELECT study) on DTC. In the study, Lenvima demonstrated a statistically significant extension in progression-free survival compared to placebo, as well as a high objective response rate.1 The most common Lenvima treatment-related adverse events were hypertension, diarrhea, fatigue or asthenia, decreased appetite, weight loss and nausea.

Discovered at Eisai’s Tsukuba Research Laboratories and developed in-house, Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR, FGFR and also RET, which are especially involved in tumor angiogenesis and proliferation of thyroid cancer. Furthermore, Lenvima has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis2.

Lenvima has already been launched in Japan, the United States and Europe, while in Asia, applications seeking marketing approval are undergoing regulatory review in Singapore, Macao, Hong Kong, Taiwan, Malaysia, India and Indonesia. Furthermore, Eisai is conducting a global Phase III study of Lenvima in hepatocellular carcinoma as well as Phase II studies of Lenvima in several other tumor types such as renal cell carcinoma and non-small cell lung cancer.

The number of patients newly diagnosed with thyroid cancer in 2012 in South Korea was estimated to be 33,000, and in Asia was estimated to be 144,000. Although treatment is possible for most types of thyroid cancer, there are few treatment options available once thyroid cancer has progressed, therefore it remains a disease with significant unmet medical needs.

Together with providing Lenvima as a new treatment option for thyroid cancer to patients in South Korea, Eisai is working to obtain marketing approval in each country in Asia. Furthermore, Eisai is committed to exploring the potential clinical benefits of Lenvima in order to further contribute to patients with thyroid cancer, and their families.

Synta Pharmaceuticals Announces Formation of Expert Oncology Panel

On October 8, 2015 Synta Pharmaceuticals Corp. (NASDAQ: SNTA) reported the formation of an Expert Oncology Panel to provide guidance on research and development strategies for the Company’s portfolio of novel oncology therapies (Press release, Synta Pharmaceuticals, OCT 8, 2015, View Source;p=RssLanding&cat=news&id=2095347 [SID:1234507676]).

Inaugural members of Synta’s Expert Oncology Panel include:

David E. Avigan, M.D. – Chief Section of Hematological Malignancies and Bone Marrow Transplantation, Beth Israel Deaconess Medical Center Associate Professor, Medicine, Harvard Medical School
Bruce Allan Chabner, M.D. – Director of Clinical Research, Cancer Center Massachusetts General Hospital Cancer Center
Jeffrey A. Engelman, M.D., Ph.D. – Director, Center for Thoracic Cancers Massachusetts General Hospital Cancer Center, Associate Professor of Medicine Harvard Medical School
F. Stephen Hodi, Jr., M.D. – Director, Melanoma Center Director, Center for Immuno-Oncology, Associate Professor of Medicine Harvard Medical School, Dana Farber Cancer Institute
Martin J. Murphy, D. MedSc, Ph.D., FASCO – Chairman and Chief Executive Officer AlphaMed Consulting, Inc.
Neil Lee Spector, M.D. – Associate Professor of Medicine, Sandra Coates Associate Professor, Associate Professor of Pharmacology & Cancer Biology, Member of the Duke Cancer Institute

"It is our pleasure to welcome a group of world-renowned physicians and scientists to our newly formed Expert Oncology Panel," said Chen Schor, President and Chief Executive Officer of Synta. "We expect that this panel will lend important perspective in translating the breadth of emerging preclinical and clinical data with ganetespib into well designed clinical studies aimed at providing meaningful clinical benefits to cancer patients in selected indications. The advice of the panel will also be important in shaping our HDC program strategy as we move towards the clinic with the first candidate from this program, STA-12-8666, and consider additional payloads for development. This distinguished expert panel, together with our newly appointed Chief Scientific Officer, Dr. Alan Rigby, is taking Synta one step further in our mission to discover, develop and commercialize oncology medicines that change cancer patients lives."

Dr. Avigan is Professor, Department of Medicine, Harvard Medical School, Chief, Hematological Malignancy and Bone Marrow Transplant section at Beth Israel Deaconess Medical Center and a co-Clinical Leader of the Leukemia Program at the Dana Farber Harvard Cancer Center. He leads a translational research program for hematological malignancies with a focus on vaccine therapy, tumor immunology, and stem cell biology with a strong track record for clinical translation of biologic based treatments. Dr. Avigan earned his M.D. from Yale University School of Medicine, completed his residency at Columbia Presbyterian Medical Center in Internal Medicine, and his fellowship at Memorial Sloan-Kettering Cancer Center in Hematology/Oncology.

Dr. Chabner is the Clinical Director, Emeritus, and Paul G. Allen Scholar at the Massachusetts General Hospital Cancer Center. During his career at the National Cancer Institute (NCI), he served as a Senior Investigator in the Laboratory of Chemical Pharmacology, Chief of the Clinical Pharmacology Branch, Director of the Clinical Oncology Program, and Director of the Division of Cancer Treatment. At the NCI, he maintained an active laboratory program in cancer pharmacology, and led the development of Taxol. His research contributed significantly to the development of high dose chemotherapy regimens, and to standard therapies for lymphoma. Dr. Chabner is the Editor in Chief for The Oncologist and serves on the executive advisory boards for some of the industry’s leading innovators in drug development. In 2006, Dr. Chabner received a presidential appointment to the National Cancer Advisory Board at the NCI, which he chaired from 2010 to 2012. Dr. Chabner earned his M.D. at Harvard Medical School, completed his residency at Brigham and Women’s Hospital, and his fellowships at the NCI and Yale-New Haven Hospital.

Dr. Engelman is the Director, Center for Thoracic Cancers at the Massachusetts General Hospital Cancer Center and an Associate Professor of Medicine at the Harvard Medical School. The overarching aim of research in the Engelman laboratory at Mass General is to develop new and more effective therapeutic strategies for the treatment of cancer, with a particular emphasis on lung cancer. Dr. Engelman is board certified in medical oncology and earned his M.D. and Ph.D. from the Albert Einstein College of Medicine. He completed his residency at Brigham and Women’s Hospital and Fellowship at the Dana Farber Cancer Institute and Massachusetts General Hospital combined program.

Dr. Hodi is the Director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber/Brigham and Women’s Cancer Center and Assistant Professor of Medicine at Harvard Medical School. He received his M.D. degree from Cornell University Medical College in 1992. Dr. Hodi competed his postdoctoral training in Internal Medicine at the Hospital of the University of Pennsylvania, and Medical Oncology training at Dana-Farber Cancer Institute where he joined the faculty in 1995. His research focuses on gene therapy, the development of immune therapies, and first into human studies for malignant melanoma. Dr. Hodi is a member of the National Comprehensive Cancer Network, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the Eastern Cooperative Oncology Group Melanoma Committee, the International Society for the Biological Therapy of Cancer, and a founding member of the Society for Melanoma Research.

Dr. Murphy is the Founding Chairman and Chief Executive Officer of AlphaMed Consulting, Inc., a consultancy that provides strategic support for academic cancer centers and cancer drug development programs of global pharmaceutical and biotechnology companies. He is the founding Executive Editor of three journals: The Oncologist, Stem Cells and of Stem Cells Translational Medicine. Dr. Murphy was founding Chief Executive Officer of Hipple Cancer Research Center and an NIH principal investigator who merited more than $25 million in competitive NIH grants. He is Co-founder of the Society for Translational Oncology, a member of the Scientific Advisory Board of Hatteras Venture Partners, a charter member of the International Advisory Board of Amsterdam’s VU University Medical Imaging Center, a charter member of Queen’s University-Belfast School of Medicine International Review Board, Chairman Emeritus of the Conquer Cancer Foundation of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), convener of ACT-China, and Steering Committee Member and Senior Consultant of the Chinese Society of Clinical Oncology. He is also a member of the National Cancer Policy Forum of the National Academy of Medicine of the United States National Academy of Sciences, a director of the Foundation for the National Institutes of Health, a member of the Board of Visitors of the UNC Lineberger Comprehensive Cancer Center, a member of the Board of Advisors of the H. Lee Moffitt Cancer Center & Research Institute and a charter member and vice chairman of C-Change, founded by former President George H.W. Bush and former First Lady Barbara Bush. Dr. Murphy is a Fellow of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and is Founding Chief Executive Officer of the non-profit CEO Roundtable on Cancer at the request of the Forty-First President George H.W. Bush.

Dr. Spector is the Sandra Coates Chair Breast Cancer Research at the Duke University Medical Center, Leader of the Developmental Therapeutics Program, Duke Cancer Institute, and currently serves as Scientific Advisor to Synta. Prior to joining Duke, Dr. Spector served as Director of GlaxoSmithKline’s Exploratory Medical Sciences in Oncology, where he successfully guided the development of Tykerb (lapatinib) and Arranon (nelarabine) from initial preclinical studies through clinical development and eventual FDA approval. Dr. Spector is board-certified in Hematology, Medical Oncology and Internal Medicine and earned his M.D. at the University of Medicine and Dentistry of New Jersey. He completed his residency in Internal Medicine at Parkland Memorial Hospital, University of Texas, Southwestern Medical Center and in Medical Oncology/Hematology at the Dana Farber Cancer Institute and Massachusetts General Hospital combined program.