On August 4, 2015 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that results from the Company’s Phase 3 VALOR trial of vosaroxin and cytarabine in 711 patients with relapsed or refractory acute myeloid leukemia (AML) were published in the The Lancet Oncology (Press release, Sunesis, AUG 4, 2015, View Source [SID:1234507010]).

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The VALOR results were first announced by the company on October 6, 2014. The article, titled "Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study" is available online first at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00201-6/abstract and will appear in the September 2015 print issue of The Lancet Oncology.

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The results published in The Lancet Oncology describe how vosaroxin plus cytarabine, based on prespecified analyses, is the first regimen to show an overall survival benefit in relapsed/refractory AML, with the greatest benefit observed in patients older than 60 years, a population with limited treatment options.

Although no significant difference was observed in the primary endpoint of overall survival (OS) between groups (unstratified analysis, median 7.5 months for vosaroxin and cytarabine [vos/cyt] vs 6.1 months for placebo and cytarabine [pla/cyt], HR=0.87, p=0.061), OS was significantly prolonged in a predefined analysis that stratified by factors used in randomization (stratified log-rank p=0.024). This was supported by a sensitivity analysis of OS censoring for subsequent transplant (median 6.7 months [vos/cyt] vs 5.3 months [pla/cyt], HR=0.81, p=0.024). Prespecified subgroup analyses according to randomization strata demonstrated that OS benefit with vosaroxin was greatest in patients age ≥60 years (7.1 months [vos/cyt] vs 5.0 months [pla/cyt], HR=0.75; p=0.0030). Median OS was not significantly different between treatment arms in patients age <60 years (HR=1.08; p=0.60).

"The results of VALOR suggest that the combination of vosaroxin and cytarabine could be an important new treatment option for salvage therapy in patients older than 60 years of age," stated Dr. Farhad Ravandi, M.D., Professor of Medicine, Department of Leukemia, University of Texas MD Anderson Cancer Center, and lead author of the publication. "This is particularly meaningful in the context of how little progress has been made in the treatment of this disease in the last forty years. In the last decade alone, no novel agents or regimens studied in randomized trials of relapsed/refractory AML have demonstrated an overall survival benefit. Given the risk-benefit demonstrated in VALOR, and the dire need in AML, I believe this combination represents an important step forward in the treatment of this disease."

The complete remission (CR) rate, the sole secondary efficacy endpoint in the VALOR trial, was significantly greater with vosaroxin (30.1% vs 16.3% with pla/cyt, p<0.0001). Combined complete remission rate was 37.1% and 18.6% for the vos/cyt and pla/cyt treatment arms, respectively (p<0.0001). Prespecified subgroup analyses demonstrated significantly higher response rates for vos/cyt-treated patients across all randomization strata except for those less than 60 years of age, with the most pronounced improvement in patients aged ≥60 years (CR: 31.9% for vos/cyt vs 13.8% for pla/cyt; p<0.0001). A higher proportion of patients in the vos/cyt arm achieved CR with study drug prior to transplant (48% vos/cyt; 32% pla/cyt). In patients with CR, median leukemia-free survival (LFS) was 11.0 months with vos/cyt vs 8.7 months with pla/cyt (HR=0.89; p=0.63). Event-free survival (EFS) was significantly prolonged in vos/cyt-treated patients (HR=0.67; p<0.0001).

Thirty-day and 60-day all-cause mortality was similar in the two treatment arms (30-day: 7.9% vs 6.6%; 60-day: 19.7% vs 19.4% for vos/cyt vs pla/cyt, respectively). Grade 3 and higher adverse events (AEs) were primarily related to myelosuppression, infection, and gastrointestinal events. Serious AEs attributed to study drug were more frequent in the vos/cyt arm, including febrile neutropenia, infections, and gastrointestinal mucosal toxicity. Importantly, there was no increase in the incidence of organ-specific toxicity (cardiac, renal, hepatic, or pulmonary) in the vos/cyt arm compared to the pla/cyt arm.

"Publication of the results from VALOR in The Lancet Oncology supports our goal of establishing vosaroxin as the first meaningful advancement in the standard of care for patients with relapsed and refractory AML," said Adam Craig, Chief Medical Officer of Sunesis. "As we work to determine a path forward toward its registration in Europe and the United States, we also look forward to the continued investigation of vosaroxin in AML, myelodysplastic syndrome and other malignancies through investigator-sponsored studies."

About the VALOR Trial
VALOR is a randomized, double-blind, placebo-controlled Phase 3 trial which enrolled 711 adult patients with first relapsed or refractory acute myeloid leukemia (AML) and was conducted at 124 leading sites in 15 countries. Patients were stratified for age, geographic region and disease status and randomized one-to-one to receive either vosaroxin and cytarabine or placebo and cytarabine.

About QINPREZO (vosaroxin)
QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.
The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

About AML
AML is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. The American Cancer Society estimates that there will be approximately 20,830 new cases of AML and approximately 10,460 deaths from AML in the U.S. in 2015. Additionally, it is estimated that the prevalence of AML across major global markets (U.S., France, Germany, Italy, Spain, United Kingdom and Japan) is over 75,000. AML is generally a disease of older adults, and the median age of a patient diagnosed with AML is about 67 years. AML patients with relapsed or refractory disease and newly diagnosed AML patients over 60 years of age with poor prognostic risk factors typically die within one year, resulting in an acute need for new treatment options for these patients.

On August 4, 2015 GlobeImmune, Inc. announced today that Celgene Corporation exercised its option under the 2009 Collaboration and Option Agreement to exclusively license GI-6207, a Tarmogen product candidate targeting cancers that express carcinoembryonic antigen (CEA) (Filing, 8-K, GlobeImmune, AUG 4, 2015, View Source [SID:1234507002]).

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GI-6207 is the second Tarmogen product candidate licensed by Celgene under the collaboration. Under the terms of the agreement, GlobeImmune will receive an option exercise payment of $1.9 million, and is eligible for regulatory and sales milestones, as well as royalties on product sales in exchange for a worldwide license. GI-6207 is currently being evaluated in a Phase 2 clinical trial at the National Cancer Institute (NCI) to evaluate GI-6207 in subjects with medullary thyroid cancer (MTC).

"We are very pleased that Celgene has exercised their option to license this program," said Timothy C. Rodell, M.D., FCCP, President and CEO of GlobeImmune, Inc. "We look forward to results from the MTC phase 2 trial in the second half of 2016."

GI-6207-02 – Phase 2 MTC Trial
GI-6207-02 is a 34 patient, randomized Phase 2 study being conducted at the NCI, which is approximately 80% enrolled. Under the protocol, patients are administered either GI-6207 for one year or observed for six months and then administered GI-6207 for one year. The primary endpoint for the trial will be the effect of GI-6207 on changes in calcitonin levels. Calcitonin is a tumor marker that correlates with tumor size in MTC. Elevated calcitonin values after surgery indicate persistent or recurrent disease. [www.clinicaltrials.gov; NCT01856920]

Medullary Thyroid Cancer
Thyroid cancer is the most common type of endocrine malignancy in the U.S. with approximately 62,450 new cases estimated in 2015. Medullary thyroid cancer, a subtype of thyroid cancer has a poor prognosis with approximately 25 percent and 10 percent of patients alive at five and ten years, respectively. Furthermore, metastatic MTC is largely unresponsive to conventional chemotherapy and radiotherapy. Two drugs have been approved for the treatment of metastatic MTC. Both of these products were approved on the basis of improved progression free survival; neither has yet shown improved overall survival, and both of them have substantial side effects that limit their use.
GI-6207

The GI-6207 is a Tarmogen that expresses a modified version of CEA protein as the target cancer antigen. CEA is over-expressed in multiple human epithelial cancers, including MTC, where studies have indicated CEA is almost universally expressed and is a diagnostic marker of the disease. Preclinical studies have shown that GI-6207 can induce an immune response to CEA as well as therapeutic anti-tumor responses. In a previous Phase 1 study of monotherapy GI-6207, 20% of subjects (5/25) had stable or decreased CEA levels and stable disease after receiving GI-6207.

On August 4, 2015, Janssen Diagnostics reported that a clinical trial involving the company’s CELLSEARCH System has been recognized by the editors of Clinical Cancer Research as being among the most significant studies to appear in the journal in its 20 year history (Press release, Johnson & Johnson, AUG 4, 2015, View Source [SID:1234506996]).

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The study revealed the prevalence of circulating tumor cells (CTCs) in most major cancers2, and established the analytical accuracy, reproducibility, and linearity of the CELLSEARCH System in capturing CTCs. This research demonstrated that the CELLSEARCH System could be used as a reliable tool to investigate CTCs and their clinical utility. The trial, "Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases," was published in 20043 and ignited interest in the clinical use of CTC testing.

The FDA cleared the CELLSEARCH System for use in the management of individuals with metastatic breast cancer, and subsequently expanded this clearance for use in the management of individuals with metastatic prostate* and colorectal cancers. To date, the CELLSEARCH System remains as the only CTC test to earn FDA clearance for use in patient management, and has also earned approval by the China FDA for the management of individuals with metastatic breast cancer.

CTCs are cancer cells that have detached from the tumor and entered the bloodstream. The highly sensitive and selective CELLSEARCH System can detect CTCs via a routine blood test. The trial referenced in Clinical Cancer Research demonstrated that these rare cells are not present in individuals without cancer. The value of capturing and counting CTCs continues to evolve as more research data is gathered about the utility of these markers in monitoring disease progression and potentially guiding more precise and personalized cancer therapy.

"Studies have repeatedly demonstrated the accuracy of CTC enumeration to predict survival in patients with metastatic breast, prostate and colorectal cancers," notes Mark C. Connelly, Ph.D., Scientific Director, Janssen Diagnostics and one of the investigators involved in the trial published in Clinical Cancer Research. "The CELLSEARCH System can help detect changes in disease progression at any time which can help oncologists and their patients make more informed clinical decisions."

Clinical data from 28 independent prospective studies involving more than 4,700 patients have validated the clinical performance and value of CELLSEARCH System CTC testing as a reliable prognostic factor for progression-free survival and overall survival both before and after therapy initiation. Data obtained with the CELLSEARCH System have been published in more than 100 peer-reviewed publications.

Intended Use: The CELLSEARCH Circulating Tumor Cell Kit is intended for the enumeration of CTC of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood. The presence of CTC in the peripheral blood is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast, colorectal or prostate* cancer. The test is intended to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring metastatic breast, colorectal and prostate cancer. Evaluation of CTC at any time during the course of disease allows assessment of patient prognosis and is predictive of progression free survival and overall survival.

*Metastatic prostate cancer patients in this study were defined as having two consecutive increases in the serum marker PSA above a reference level, despite standard hormonal management. These patients are commonly described as having androgen-independent, hormone-resistant, or castration-resistant prostate cancer.