On October 6, 2014 Sunesis Pharmaceuticals reported the results from the pivotal Phase 3 VALOR trial (NCT01191801), a randomized, double-blind, placebo-controlled trial of vosaroxin and cytarabine in patients with first relapsed or refractory acute myeloid leukemia (AML) (Press release Sunesis, OCT 6, 2014, View Source [SID:1234500789]). At more than 100 leading international sites, the trial enrolled 711 patients, who were stratified for age, geography and disease status. The trial did not meet its primary endpoint of demonstrating a statistically significant improvement in overall survival, with a median overall survival of 7.5 months for vosaroxin and cytarabine compared to 6.1 months for placebo and cytarabine (HR=0.865, p=0.06). Because transplant may confound the primary analysis, a predefined analysis of overall survival censoring for stem cell transplantation was planned. In this analysis, patients receiving the vosaroxin combination had a median overall survival of 6.7 months versus 5.3 months for placebo and cytarabine (HR=0.809, p=0.02). The trial also demonstrated a clinically significant benefit in complete remission (CR) rate (30.1% vs 16.3%, p=0.0000148), the secondary endpoint.

For age, the trial stratified patient populations into age 60 years and older and younger than 60 years at enrollment. Within a predefined analysis of patients younger than 60 years (n=260), where the rate of stem cell transplant was 45.8%, the vosaroxin combination demonstrated a median overall survival of 9.1 months, versus 7.9 months for placebo and cytarabine (HR=1.079, p=NS), and a CR rate of 26.9% versus 20.8% (p=0.24). In the analysis of patients aged 60 years and older (n=451), where the rate of stem cell transplant was 20.2%, the vosaroxin combination demonstrated a median overall survival of 7.1 months, versus 5.0 months for placebo and cytarabine (HR=0.755, p=0.006), and a CR rate of 31.9% versus 13.8% (p=0.0000048).

In the intent-to-treat population, Grade 3 or higher non-hematologic adverse events that were more common in the vosaroxin combination arm were gastrointestinal and infection-related toxicities, consistent with those observed in previous company trials. The rate of serious adverse events was 55.5% in the vosaroxin combination arm compared to 35.7% in the placebo and cytarabine arm. Thirty-day and 60-day all-cause mortality were comparable between the trial arms (7.9% versus 6.6% and 19.7% versus 19.4%, for the vosaroxin combination versus placebo and cytarabine, respectively).

Based on results of the trial, Sunesis plans to commence a marketing authorization application with the European Medicines Agency (EMA) and to meet with the U.S. Food and Drug Administration to determine the appropriate regulatory path forward.

The results reported above are based upon Sunesis’ analysis of the data to date. Detailed results of the VALOR trial will be submitted for presentation at an upcoming medical conference.

“VALOR was a robust, well-conducted trial, among the largest in the relapsed or refractory AML setting. The study outcomes are very encouraging, and I look forward to a full presentation of the data in a peer-reviewed forum,” said Robert Stuart, M.D., Professor of Medicine, Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, an investigator in the VALOR study and chairman of the study’s steering committee. “The clinical benefit is particularly impressive in patients aged 60 years and older, a population for whom there is no therapeutic standard of care.”

“There remains an acute need for new treatment options in AML, particularly relapsed refractory patients, where no therapy has demonstrated a survival benefit in a pivotal Phase 3 trial in more than 40 years,” said Adam Craig, M.D., Ph.D., Executive Vice President, Development and Chief Medical Officer of Sunesis. “While we continue to evaluate the findings of VALOR in their totality, we believe the results demonstrate a clinically meaningful and important advancement in the treatment of this disease.”

“We are deeply grateful for the support and commitment of the AML investigators, the patients and families who took part in or contributed to VALOR,” said Daniel Swisher, Chief Executive Officer of Sunesis. “We look forward to presenting these data in detail to regulators in both Europe and the U.S. and to reporting on our progress and plans as they develop.”

On October 6, 2014 Bristol-Myers Squibb Company reported the establishment of a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of combining Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor Opdivo (nivolumab) with three molecularly targeted oncology therapies (Zykadia (ceritinib), INC280 and EGF816) from Novartis (Press release Bristol-Myers Squibb, OCT 6, 2014, View Source [SID:1234500788]). Novartis will conduct two Phase 1/2 studies focused on non-small cell lung cancer (NSCLC).

“Bristol-Myers Squibb is committed to advancing the science, research and development of immunotherapy as an innovative approach to treating cancer in multiple tumor types,” said Michael Giordano, senior vice president, Oncology Development, Bristol-Myers Squibb. “Combining Opdivo with select targeted agents from Novartis complements our broad global development strategy of immuno-oncology combinations across the spectrum of lung cancer settings, and supports our goal of improving outcomes for patients. We look forward to working with Novartis to fully explore how the combination of these agents can potentially advance care for lung cancer patients.”

One trial will evaluate the combination of Opdivo with Zykadia (ceritinib), an FDA-approved treatment for patients with anaplastic lymphoma kinase-positive (ALK+) metastatic NSCLC who have progressed on or are intolerant to crizotinib. A second study will investigate Opdivo with INC280, a potent and highly selective inhibitor of c-MET receptor tyrosine kinase, and EGF816, a potent, third-generation EGFR tyrosine kinase inhibitor that is active against T790 mutations. INC280 and EGF816 are currently being investigated in various Phase 1/2 NSCLC trials.

Opdivo is part of a new class of cancer treatments known as immunotherapies designed to harness the body’s own immune system in fighting cancer, and targets distinct regulatory components of the immune system. Zykadia, INC280 and EGF816 have each demonstrated evidence of targeting specific molecules responsible for tumor growth in NSCLC patient populations. Despite advancements, treatment for lung cancer remains a significant medical need, and the studies will explore the potential of enhanced anti-tumor response using a combined immunotherapy and targeted molecular approach. Bristol-Myers Squibb has proposed the name Opdivo (pronounced op-dee-voh), which, if approved by health authorities, will serve as the trademark for nivolumab.

Additional details of the collaboration were not disclosed.

On October 6, 2014 Bristol-Myers Squibb and The University of Texas MD Anderson Cancer Center reported a novel clinical research collaboration to evaluate multiple immunotherapies, including Opdivo (nivolumab), Yervoy (ipilimumab) and three early-stage clinical immuno-oncology assets from Bristol-Myers Squibb, as potential treatment options for acute and chronic leukemia as well as other hematologic malignancies (Press release Bristol-Myers Squibb, OCT 6, 2014, View Source [SID:1234500786]).

The agreement represents an innovative approach to research by focusing numerous clinical trials using multiple agents, in mono and combination regimens, on a specific disease target, in this case select hematologic malignancies. Through this approach, Bristol-Myers Squibb and MD Anderson aim to benefit patients by expediting the delivery of new therapies. The collaboration will launch up to 10 phase 1 and 2 clinical trials, conducted by MD Anderson, focused on evaluating investigational immune-based approaches for acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS) and myelofibrosis (MF). Additional studies will be determined by the collaboration at a later date.

Opdivo (nivolumab) is an investigational PD-1 immune checkpoint inhibitor currently approved in Japan for the treatment of patients with unresectable melanoma, and Yervoy (ipilimumab) is a CTLA-4 immune checkpoint inhibitor approved in the U.S. and more than 40 countries for patients with unresectable or metastatic melanoma. Bristol-Myers Squibb has proposed the name Opdivo (pronounced op-dee-voh), which, if approved by health authorities, will serve as the trademark for nivolumab.

“Collaborations between industry and academia can offer a faster and broader spectrum of clinical trials to benefit patients,” said Hagop Kantarjian, M.D., chair of leukemia at MD Anderson. “We hope innovative collaborations such as this can help lead to a higher likelihood for success across the board and will speed up the clinical development of new compounds for delivery to the patients who need them.”

“Immunotherapy is an extremely promising area of research and a key area of focus for MD Anderson’s Moonshots Program,” said MD Anderson President Ron DePinho, M.D. “Partnerships between academia and industry have the potential to significantly advance the application of new discoveries to cancer treatment.”

“Bristol-Myers Squibb is committed to advancing the field of immuno-oncology and complementing our broad research and discovery programs through innovative collaborations with partners who share our commitment to patients,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer, Bristol-Myers Squibb. “Cooperation between industry and academia offers a tremendous opportunity to strengthen our scientific and clinical understanding of the role of the immune system in treating cancer.”

Immuno-oncology is an innovative approach to cancer research and treatment that is designed to harness the body’s own immune system to fight cancer. Hematologic malignancies represent significant areas of high unmet need marked by poor outcomes among the elderly, high-risk patients and for those with multiple relapses. Existing clinical research, including studies by MD Anderson, support further research into the potential of immunotherapies as treatment options for leukemia and other hematologic malignancies.

On October 6, 2014 ARIAD Pharmaceuticals and Bellicum Pharmaceuticals reported a restructuring of their license agreement for ARIAD’s cell-signaling technology (Press release Ariad, OCT 6, 2014, View Source [SID:1234500785]). ARIAD will receive $50 million in exchange for a fully paid up license to this technology and return of its equity stake in closely held Bellicum. The scope of the license and the field of use were also expanded as part of the amendment.

Under the terms of the revised agreement, ARIAD will receive $50 million in three installments: $15 million upon signing of the agreement, $20 million by June 30, 2015, and $15 million by June 30, 2016. The last payment may be accelerated to the fourth quarter of 2015 under certain circumstances. The restructured agreement gives Bellicum a worldwide exclusive license to ARIAD’s cell-signaling technology for broad use in human cell therapies for all diseases on a royalty- and milestone-free basis.

ARIAD’s technology involves the use of a small-molecule drug, such as AP1903, to activate cell signaling and other cellular events. Bellicum is developing controllable stem-cell transplant, chimeric-antigen receptor (CAR) T cell and cancer vaccine product candidates in a variety of blood and solid tumor cancers and in non-malignant genetic diseases.

“This license restructuring allows Bellicum to fully exploit our specialized cell signaling switches and related platforms, free of future royalty or milestone obligations to ARIAD,” stated Tom Farrell, Bellicum’s chief executive officer. “The expanded license also includes additional cell-signaling technology that may enable future products with dual control switches.”

“The amended agreement with Bellicum allows ARIAD to realize substantial non-dilutive funding from our legacy program based on small-molecule regulation of cell signaling, while maintaining our strategic focus on bringing breakthrough medicines to cancer patients in need,” said Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD.

Outside the Bellicum field of use, ARIAD has also licensed certain aspects of the technology to REGENXBIO, Inc., and Clontech Laboratories, Inc. These license agreements remain unchanged.