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Roche launches the cobas EGFR Mutation Test v2 for use with either plasma or tumour tissue samples

On September 28, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the commercial availability in countries that accept the CE mark1 of the cobas EGFR Mutation Test v2, the first oncology assay from Roche that utilises either plasma or tumour tissue as a sample (Press release, Hoffmann-La Roche , SEP 28, 2015, View Source [SID:1234507568]). The test identifies 42 mutations in the epidermal growth factor receptor (EGFR) gene, the most of any In-vitro Diagnostic (IVD) on the market, and can also be used as an aid in selecting eligible patients with non-small cell lung cancer (NSCLC) for therapy with an EGFR tyrosine kinase inhibitor (TKI).

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"As more targeted therapies become available, it is critical that we provide innovative molecular testing methods that make it easier for patients to get tested, regardless of the surgery risks or tumour tissue availability," said Roland Diggelmann, COO, Roche Diagnostics. "By investing in liquid biopsy research and developing the cobas EGFR Mutation Test v2 for use with either plasma or tissue samples, Roche is helping to remove these common barriers from molecular testing."

According to a recent survey of more than 550 oncologists, EGFR genetic testing is not being conducted in about 25 percent of patients with NSCLC2,3. Some of the reasons for not testing included lack of diagnostic material and cases where a patient was deemed unfit to undergo biopsy. With the cobas EGFR Mutation Test v2 being validated with both tissue and plasma sample types, patients who previously did not qualify for biopsy now have the opportunity to receive a result from a simple plasma test to guide the corresponding therapy.

The cobas EGFR Mutation Test v2 is available now in countries that accept the CE mark1. For more information, please visit www.cobas-egfrtestv2.com.

About the cobas EGFR Mutation Test v2
The cobas EGFR Mutation Test v2 is a real-time PCR test that identifies 42 mutations in exons 18-21, including L858R, exon 19 deletions, L861Q and the TKI-resistance mutation, T790M. It is designed to enable testing of either tissue or plasma specimens with one kit, and allows labs to mix-batch tissue and plasma on the same plate. Additionally, Roche has developed a cell-free DNA (cfDNA) sample preparation kit that is optimised for extracting the DNA from plasma.

When testing plasma with the cobas EGFR Mutation Test v2, a new feature called the Semi-Quantitative Index (SQI) is included in the report. This number is designed to reflect a trend in the amount of mutant cfDNA in the sample. When frequently testing for the EGFR mutation using the test, tracking the SQI value and identifying a trend may lead to understanding tumour progression.
The cobas EGFR Mutation Test v2 is designed to run on the cobas 4800 System, v2.1 or higher. The system can also be used for the detection of mutations in the KRAS and BRAF gene of tumour samples.

REPEAT/Actor Jack Huston Challenges Europeans to Take ACTion Against Lung Cancer

On September 28, 2015 Bristol-Myers Squibb reported that actor Jack Huston, a star of the hit television show Boardwalk Empire and the upcoming remake of Ben Hur, took on an important new role as lung cancer advocate as he challenged Europeans to A.C.T. – be Aware, get Checked, and Talk with their doctor about lung cancer. After losing his grandfather to lung disease and his best friend and mentor, Peter Blythe, to lung cancer, Huston was motivated to take action by partnering with Bristol-Myers Squibb Company (NYSE:BMY) and leading advocacy group Lung Cancer Europe (LuCE) to ask the public, particularly those at high risk, what’s their Next Lung Cancer A.C.T.?

Lung cancer is the number one cancer killer in Europe with an estimated 353,000 deaths each year – more than breast cancer, colorectal and prostate cancers combined. In Europe, lung cancer is the third most common cancer among women. Despite the growing prevalence, a new survey conducted among more than 8,200 participants in nine European countries showed that lung cancer knowledge is very low, with nearly six in 10 people (57%) surveyed saying that they are not knowledgeable about the disease. Further, one in five people (20%) could not identify the symptoms of lung cancer, including persistent cough, and one in 10 people (10%) do not know the risk factors, such as exposure to cigarette smoking.

Huston, along with lung cancer advocates and oncologists, unveiled the survey results at the European Cancer Congress (ECC) 2015 in Vienna, as well as a short film highlighting the personal stories of lung cancer patients.

"Like many Europeans, I know firsthand the devastating impact cancer can have on a family," said Huston. "I’ve joined The Next Lung Cancer A.C.T. in hopes of encouraging others to be mindful of the risk factors and symptoms of lung cancer and the importance of taking action now."

Key findings of the survey showed:

Six in 10 respondents (62%) believe lung cancer is a smoker’s disease, although smoking is only one risk factor for lung cancer
45 percent believe that breast cancer is the leading cause of death among women as compared to 8 percent who responded lung cancer

Nearly half of all respondents (46%) said they are not concerned about getting lung cancer, including 43 percent who have experience with lung cancer and 36 percent who are daily smokers
Eight in 10 people (83%) have never spoken to their doctor about lung cancer; an equal number of smokers (77%) also report this behavior

Following the survey, the majority of respondents (90%) expressed a willingness to take action to reduce their risk of lung cancer, including reducing their exposure to carcinogen (cancer-causing substances or agents) (50%), limit exposure to secondhand smoke (48%), and talking to their doctor (43%)

"It’s a pivotal time for lung cancer – the disease remains an enormous public threat in Europe but we are seeing promising research in the lung cancer space," said LuCE board member and lung cancer survivor, Regine Deniel Ihlen. "That is why now is the time for people to act by being aware, taking steps to get checked and having an ongoing dialogue with their physicians."

"At ECCO we are committed to helping people understand the signs that indicate that they may have cancer, as well as recognizing ways in which the disease may be prevented," said Professor Martine Piccart, President of the European CanCer Organization (ECCO). "That is why we are happy to be hosting the launch of this campaign, and we wish it every success."

"At Bristol-Myers Squibb, we are committed to fighting lung cancer through our research in oncology and by supporting the global lung cancer community," said Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb. "The Next Lung Cancer A.C.T. represents our ongoing dedication to helping to empower those with cancer by providing them with knowledge to better understand the risks of lung cancer and how to take action."

About The Next Lung Cancer A.C.T.

The Next Lung Cancer A.C.T. is a public awareness campaign designed to encourage the public, particularly those at high risk of lung cancer, to take ACTion against the disease by being Aware, getting Checked and Talking to their doctor. The Next Lung Cancer A.C.T. is sponsored by Bristol-Myers Squibb, in collaboration with Lung Cancer Europe (LuCE). For more information on the campaign please visit www.TheNextLungCancerACT.eu.

About the Survey and TNS

TNS conducted the survey. TNS, the world’s largest custom research agency, is a well-recognized research group for their quality and authoritative research.

Participants in the 12-question, self-administered online omnibus survey were 8,263 Europeans, ages 16-54 across nine different countries in Europe: Austria, Denmark, Germany, Great Britain, Italy, Netherlands, Spain, Switzerland and Turkey. The survey was conducted between July 30, 2015 and August 7, 2015. The results were tested at 95% significant. At 95% confidence level, if the study were repeated, the results would not fluctuate more than 3.0-3.4 percentage points in either direction for the population surveyed in each country.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization (WHO). In Europe alone, lung cancer is responsible for an estimated 353,000 deaths from the disease every year – more than breast cancer, colorectal and prostate cancers combined. It has the highest economic burden of all cancers in the European Union, costing an estimated €18.8 billion or 15 percent of overall cancer costs.

Aeterna Zentaris’ Zoptarelin Doxorubicin Meets Phase 2 Primary Endpoint in Men with Heavily Pretreated Castration and Taxane Resistant Prostate Cancer

On September 28, 2015 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") reported that its lead oncology compound, zoptarelin doxorubicin (formerly AEZS 108), met the primary end-point of the investigator-driven and sponsored Phase 2 clinical trial in Castration and taxane Resistant Prostate Cancer (CRPC) and demonstrated good tolerability (Press release, Verastem, SEP 28, 2015, View Source [SID:1234507593]). The primary endpoint was Clinical Benefit (CB) defined as remaining progression-free by RECIST and Prostate Specific Antigen (PSA) after treatment for 12+ weeks.

Results were presented this morning by lead investigator, Jacek Pinski, MD, PhD, of the USC Norris Comprehensive Cancer Center, during a poster session at the 18th ECCO – 40th ESMO (Free ESMO Whitepaper) European Cancer Congress in Vienna, Austria.

David A. Dodd, Chairman and CEO of Aeterna Zentaris, commented, "We are encouraged with the Phase 2 results for zoptarelin doxorubicin in prostate cancer. Because luteinizing hormone-releasing hormone receptors are expressed in a great number of cancers including prostate cancer, we believe that zoptarelin doxorubicin, which specifically targets those receptors, may represent a novel targeted treatment for men with this disease. These Phase 2 results in prostate cancer, as well as prior positive Phase 2 results in endometrial and ovarian cancer, are further demonstration of the potential of this innovative compound in a variety of cancer indications for both men and women."

Study Design

This was a single-arm Simon Optimum design Phase 2 study of zoptarelin doxorubicin in 25 patients with CRPC. Patients received zoptarelin doxorubicin (210 mg/m2) intravenously over 2 hours, every 3 weeks. The primary endpoint was CB, defined as remaining progression-free by RECIST and PSA after treatment for 12+ weeks. Secondary endpoints were progression free survival (PFS), best overall response, toxicity, pain and overall survival (OS).

Results

Twenty patients had measurable disease, with a median of 1 prior chemotherapy regimens and a median PSA of 255.8 ng/ml. Eleven patients experienced CB; 13 patients achieved stable disease. Median PFS and OS were 4.4 months (95% CI: 3.6, 5.5) and 6 months (95% CI: 4.2, 10.7) respectively. Forty-four percent of patients demonstrated improvement of pain score at 12 weeks. Maximal PSA response was stable in 20 patients. Zoptarelin doxorubicin demonstrated good tolerability with grade 3-4 hematologic (n=7) and grade 3 blood and lymphatic system disorders (n=5) adverse events as the most common events.

Titled, "A Phase 2 Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer", Liu SV, Tsao Wei DD, Xiong S, Groshen S, Dorff TB, Quinn DI, Tai YC, Engel J, Hawes D, Schally AV, Pinski J, the poster is available at this link.

About Zoptarelin Doxorubicin

Zoptarelin doxorubicin represents a new targeting concept in oncology using a hybrid molecule composed of a synthetic peptide carrier and a well-known chemotherapy agent, doxorubicin. Zoptarelin doxorubicin is the first intravenous drug in advanced clinical development that directs the chemotherapy agent specifically to LHRH-receptor expressing tumors, which could result in a more targeted treatment with less damage to healthy tissue. The Company is currently conducting a fully-enrolled ZoptEC (Zoptarelin doxorubicin in Endometrial Cancer) Phase 3 trial in women with advanced, recurrent or metastatic endometrial cancer; results from a second interim analysis of this trial are expected in October 2015. Zoptarelin doxorubicin is also in an investigator initiated Phase 2 trial in prostate cancer. Aeterna Zentaris owns the worldwide rights to this compound except in China (including Hong Kong and Macau) where rights have been out-licensed to Sinopharm A-Think Pharmaceuticals, a subsidiary of Sinopharm, the largest medical and healthcare group in China and on Fortune’s Global 500 list. On April 16, 2015, the Company announced the filing of a patent application intended to strengthen the exclusivity of zoptarelin doxorubicin through a unique, significantly lower cost in the manufacturing process.

About Prostate Cancer

According to the American Cancer Society, prostate cancer is the second most common cancer in men worldwide, affecting approximately one in six males. It is estimated that there will be approximately 220,800 new cases of prostate cancer in the United States in 2015. While prostate cancer is prevalent among men of all ages and races, African Americans and men older than 65 have a higher rate of diagnosis.

Verastem Stops Enrollment Due to Futility in the COMMAND Study of VS-6063 for the Treatment of Malignant Pleural Mesothelioma

On September 28, 2015 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, reported that the Company has stopped enrollment in the Phase 2 registration-directed, double-blind, placebo-controlled study (COMMAND) of VS-6063 for patients with mesothelioma (Press release, Verastem, SEP 28, 2015, View Source [SID:1234507592]). The decision to stop enrollment for futility followed a Data Safety Monitoring Board (DSMB) review of a pre-planned interim analysis. The results of the analysis demonstrated that VS-6063 had a generally well tolerated safety profile but that there was not a sufficient level of efficacy to warrant continuation of the study.

"Malignant pleural mesothelioma is among the most aggressive and lethal cancers with only one approved therapy," said Lou Vaickus, MD FACP, Interim Chief Medical Officer. "With the aggressiveness of this disease, the use of single agent VS-6063 as a maintenance treatment following chemotherapy where all patients had residual disease was not sufficient. There remains a significant unmet medical need for new treatment options for patients suffering from this very complex, difficult-to-treat cancer."
"We have stopped further enrollment and initiated an orderly wind-down of the COMMAND study," said Robert Forrester, Verastem President and Chief Executive Officer. "We are disappointed with the COMMAND outcome, but we are deeply grateful for the support and commitment from the patients participating in the study, their families, and the study investigators. Based on these results, we will reevaluate our clinical priorities and direct our resources toward further development of VS-6063, VS-4718, and VS-5584."

As of the end of Q2 2015, Verastem had $132.1M in cash and cash equivalents.

SYNDAX AND MERCK ANNOUNCE FIRST PATIENTS DOSED IN PHASE 1b/2 CLINICAL TRIAL OF ENTINOSTAT AND KEYTRUDA®

On September 28, 2015 Syndax Pharmaceuticals, Inc. and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported the dosing of the first patients in the Phase 1b/2 clinical trial of Syndax’s entinostat in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with non-small cell lung cancer (NSCLC) or melanoma (Press release, Merck & Co, SEP 28, 2015, View Source [SID:1234507590]). The clinical trial, designated ENCORE 601 by Syndax and KEYNOTE 142 by Merck, is evaluating the safety, tolerability and efficacy of entinostat, an oral, small molecule that targets immune regulatory cells, combined with KEYTRUDA, an anti-programmed cell death protein 1 (anti-PD-1) antibody.

"This is an important clinical milestone for Syndax and our collaboration with Merck that was achieved on schedule with our joint development plan," said Michael L. Meyers, M.D., Ph.D., Syndax’s Chief Development Officer. "As entinostat has been shown in preclinical models to reduce the number and inhibit the function of host immune suppressor cells, we believe that entinostat combined with KEYTRUDA could result in an improved response rate for the combination compared to either agent alone. The initiation of this trial advances our immuno-oncology program developing entinostat as a potential combination therapy in multiple cancer indications with an initial focus on tumors that have shown sensitivity to immunotherapy."

"Our collaboration with Syndax exemplifies our interest in exploring innovative therapeutic combinations with KEYTRUDA," said Eric Rubin, M.D., vice president and therapeutic area head, early-stage oncology development, Merck Research Laboratories. "We are pleased with the rapid initiation and progress being made by Syndax towards gaining a better understanding of the potential of KEYTRUDA and entinostat in these difficult-to-treat patient populations."

The ENCORE 601/KEYNOTE 142 trial is designed as a Phase 1b/2 open label clinical trial with dose escalation for entinostat, in which the Phase 1b portion will evaluate the safety and tolerability of the combination of entinostat and KEYTRUDA in patients with NSCLC, and the Phase 2 portion will assess the safety and preliminary efficacy of the combination in separate cohorts in patients with NSCLC or melanoma. The trial will be conducted in the United States and is expected to enroll up to 178 patients.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until metabolic control is achieved.

Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. The following clinically significant immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis.

For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients. Adverse reactions, reported in at least two patients, that led to discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients. The most frequent serious adverse reactions, reported in 2% or more of patients, were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA. It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.