On December 7, 2015 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported new study findings investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in combination with lenalidomide and low-dose dexamethasone (two commonly used treatments for multiple myeloma) in patients whose disease has progressed after at least two lines of prior therapy, including a proteasome inhibitor and an IMiD (immune modulatory drug) (Press release, Merck & Co, DEC 7, 2015, View Source [SID:1234508450]). The initial findings from the ongoing Phase 1 KEYNOTE-023 study showed an overall response rate (ORR) of 76 percent (n=13/17), as assessed by the International Myeloma Working Group (IMWG) 2006 Criteria. These results will be presented today at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Jesus San Miguel, M.D., Ph.D., Clínica Universidad de Navarra, Pamplona, Spain (Abstract #505). Based in part on these data, Merck has initiated two Phase 3 studies evaluating KEYTRUDA in the treatment of multiple myeloma.

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"Many patients with multiple myeloma relapse after their initial treatment, reinforcing the need for additional treatment options," said Dr. Jesus San Miguel. "These findings highlight the potential of combining KEYTRUDA with an IMiD and dexamethasone in patients who have multiple myeloma."

"Our clinical program explores the potential for KEYTRUDA across broad patient populations, including in combination with other medicines," said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "We are encouraged by these results, showing responses in patients who have relapsed following treatment for multiple myeloma when treated with KEYTRUDA in combination with lenalidomide and dexamethasone, and look forward to building on these data."

Results from KEYNOTE-023 Presented at ASH (Free ASH Whitepaper)

In the study with 50 heavily pre-treated patients, initial findings from 17 patients who were treated with KEYTRUDA (pembrolizumab) in combination with lenalidomide and low-dose dexamethasone demonstrated an ORR of 76 percent (n=13/17) (per IMWG 2006), including four very good partial responses (24%) and nine partial responses (53%).

Adverse events in all 50 patients were consistent with previously reported safety data for KEYTRUDA as well as lenalidomide and low-dose dexamethasone. Grade 3 or 4 treatment-related adverse events included: neutropenia (n=11), thrombocytopenia (n=4), diarrhea (n=1), fatigue (n=1), anemia (n=4), hyperglycemia (n=3) and muscle spasms (n=1). Immune-mediated adverse events included: adrenal insufficiency (n=1), hyperthyroidism (n=2), hypothyroidism (n=2), and thyroiditis (n=1). No treatment-related deaths were reported.

About the KEYTRUDA Development Program and KEYNOTE-023

Merck is conducting a broad hematological malignancy program with approximately 20 clinical trials, including four registration-enabling studies and more than 15 combinations across a variety of lymphomas, myeloma, leukemia, and other hematologic malignancies. Registration-enabling trials of KEYTRUDA are currently enrolling patients in melanoma, NSCLC, head and neck cancer, bladder cancer, gastric cancer, colorectal cancer, esophageal cancer, breast cancer, Hodgkin lymphoma, multiple myeloma and other tumors, with further trials in planning for other cancers.

KEYNOTE-023 is a global, open-label, Phase 1 study designed to evaluate KEYTRUDA treatment in combination with dexamethasone and two different doses of lenalidomide in approximately 75 patients with relapsed/refractory multiple myeloma (RRMM). Patients will receive KEYTRUDA (2 mg/kg every two weeks) in combination with lenalidomide (10 mg or 25 mg) or KEYTRUDA (200 mg fixed dose every two weeks) with lenalidomide (10 mg or 25 mg); all patients will receive 40 mg low-dose dexamethasone weekly. Primary endpoints include safety and tolerability; secondary endpoints include ORR, duration of response, progression-free survival (PFS), and overall survival (OS).

About Multiple Myeloma

Multiple myeloma is a cancer of blood plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body. Manifestations of the disease often include bone pain and fractures, and may include kidney problems, a weakened immune system weakness, and confusion. Multiple myeloma is the second most common blood cancer. In 2015, an estimated 26,850 people are expected to be diagnosed and an estimated 11,240 people are expected to die of the disease in the U.S. alone.

About KEYTRUDA (pembrolizumab) Injection 100 mg

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is also indicated at the same dosing for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These indications are 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 these indications may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 12 (2.9%) of 411 melanoma patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis in patients, 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 or recurrent Grade 2 pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients with melanoma, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Colitis occurred in 4 (0.7 %) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis in patients 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 occurred in patients receiving KEYTRUDA. Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients with melanoma, 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 with melanoma, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or Grade 4 hypophysitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients with melanoma, 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 with melanoma, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%). 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 replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 3 (0.7%) patients with melanoma, 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. 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. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following steroid taper. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Across clinical studies with KEYTRUDA, the following clinically significant, immune-mediated adverse reactions have occurred: bullous pemphigoid and Guillain-Barré syndrome. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients with melanoma treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

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 can 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.

Among the 411 patients with metastatic melanoma, 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%).

Among the 550 patients with metastatic NSCLC, KEYTRUDA was discontinued due to adverse reactions in 14% of patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), decreased appetite (25%), dyspnea (23%), and cough (29%).

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 and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On December 07, 2015 Radius Health, Inc. (Nasdaq:RDUS), a science-driven biopharmaceutical company focused on developing new therapeutics for patients with osteoporosis and serious endocrine-related diseases, including hormone-responsive breast cancer,reported that it will host a conference call and webcast on Thursday, December 10, 2015, at 8 PM EST to provide an update on new data being presented on the investigational drug RAD1901 at the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX, December 8-12 (Press release, Radius, DEC 7, 2015, View Source [SID:1234508470]).

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RAD1901 is an investigational oral, selective estrogen receptor degrader (SERD) being evaluated for the potential treatment of hormone-driven, or hormone-resistant, metastatic breast cancer. RAD1901 has demonstrated potent single-agent and combination efficacy in ER+ primary patient derived xenograft animal models, including those harboring ESR1 mutations. These preclinical results, together with ongoing clinical data from Phase I monotherapy dose escalation trials, strongly support the further investigation of RAD1901 in patients with ER+ and endocrine-resistant disease.

RAD1901 Poster Presentation Details:

Title: RAD1901, a Novel Oral, Selective Estrogen Receptor Degrader ("SERD") with Single Agent Efficacy in ER+ Primary Patient Derived ERS1 Mutant Xenograft Model
Abstract Number: P3-05-07
Session/Poster: Poster Session 3, Tumor Cell and Molecular Biology: Endocrine Therapy and Resistance
Date and Time: Thursday, December 10, 2015, 5:00 PM – 7:00 PM CT (6:00 PM – 8:00 PM ET)
Location: Henry B. Gonzalez Convention Center, Halls A-B

Title: A Phase 1 Study of RAD1901, a Novel, Orally Available, Selective Estrogen Receptor Degrader, for the Treatment of ER Positive Advanced Breast Cancer
Abstract Number: OT2-01-10
Session/Poster: Ongoing Clinical Trials: Ongoing Trials — Endocrine Therapies
Date and Time: Thursday, December 10, 2015 5:00 PM – 7:00 PM CT (6:00 PM – 8:00 PM ET)
Location: Henry B. Gonzalez Convention Center, Halls A-B

Title: A Phase 1 Dose Escalation Study of RAD1901, an Oral Selective Estrogen Receptor Degrader, in Healthy Postmenopausal Women
Abstract Number: P6-13-02
Session/Poster: Poster Session 6, Treatment: New Drugs and Treatment Strategies
Date and Time: Saturday, December 12, 2015, 7:30 AM – 9:00 AM CT (8:30 AM – 10:00 AM ET)
Location: Henry B. Gonzalez Convention Center, Hall C

Conference Call and Webcast

Radius will host a conference call and live audio webcast at 8:00 PM ET (7:00 PM CT) on Thursday, December 10, 2015 to provide an update on the RAD1901 data being presented at SABCS.

Conference Call and Webcast Information:
Date: Thursday, December 10, 2015
Time: 8:00 PM ET (7:00 PM CT)
Domestic Dial-in Number: 1-877-705-6003
International Dial-in Number: 1-201-493-6725
Live webcast: View Source

Replay of the call information:
Domestic Dial-In Number: 1-877-870-5176
International Dial-in Number: 1-858-384-5517
Replay Pin Number 13626630

On December 7, 2015 Nemucore Medical Innovations, Inc., a privately held, clinical-stage biopharmaceutical company dedicated to the development of therapies targeting multi-drug resistant cancers with a special emphasis on highly lethal women’s cancers, reported the completion of an option agreement with Cancer Research Technology Ltd (CRT), the commercial arm of Cancer Research UK, for the exclusive license of worldwide commercial rights to GSK1070916 (now designated NMI-900 by Nemucore), a potent Aurora B/C kinase inhibitor targeting a broad range of cancers (Press release, Cancer Research Technology, DEC 7, 2015, View Source [SID1234523201]).

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"We are thrilled to be able to build on the excellent foundational clinical research conducted by Cancer Research UK, and continue the development of this innovative and very promising anticancer therapeutic," said Timothy P. Coleman, Ph.D., Chairman, Chief Executive Officer and President of Nemucore. "Based on its unique properties and pharmaceutical profile, we believe NMI-900 has best-in-class potential as a breakout therapy for treating women’s and other cancers associated with high mortality rates that have already been demonstrated to be intractable to conventional therapeutics."

NMI-900 is a potent ATP-competitive inhibitor of Aurora B kinase that has demonstrated high affinity for Aurora B, a significantly slower dissociation rate compared to its peers, potent anti-proliferative activity in multiple cancer cell lines, and minimal effects on non-proliferating normal human cells. In 2014, Cancer Research UK’s Centre for Drug Development successfully completed a Phase 1/2a trial of NMI-900. In this trial, NMI-900 elicited response in 61% of patients with no remaining standard therapies available to them across a wide variety of advanced and/or metastatic solid tumors. NMI-900 was well tolerated, with the most prevalent adverse event presenting as predictable and treatable neutropenia. NMI-900 was developed by Cancer Research UK’s Centre for Drug Development in partnership with GSK, under the Clinical Development Partnerships (CDP) initiative. This initiative, a joint effort launched by Cancer Research UK and Cancer Research Technology Ltd, provides a simple route for companies to progress oncology agents that would not otherwise be developed, and increase the number of clinical trials being undertaken for the treatment of cancer.

Dr. Keith Blundy, CEO of Cancer Research Technology commented, "We’re very pleased that Nemucore plans to take this promising new drug candidate and develop it through more clinical trials so that it has a greater chance of reaching patients who are in urgent need of new treatment options, sooner. The drug forms part of our Clinical Development Partnerships initiative, and is one of twelve drugs on the scheme that are moving out of the lab into clinical trials – something that wouldn’t have been possible otherwise."

Nemucore expects to initiate a Phase 2b clinical trial of NMI-900 in patients with advanced, platinum-resistant ovarian cancer in mid-2016 based on the supportive preclinical and early clinical trial results. As part of their clinical development and commercial strategy, the Company is concurrently developing a companion diagnostic with the Medical Prognosis Institute to identify patients most likely to respond to NMI-900. Nemucore expects to investigate the efficacy of NMI-900 in the treatment of EGF receptor-positive non-small cell lung cancer (NSCLC), myelodysplastic syndrome (MDS) and other difficult-to-treat cancers in the future.

On December 7, 2015 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that eleven posters for the Prosigna Breast Cancer Gene Signature Assay and the PAM50 gene signature, the basis for Prosigna, will be presented at the 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) (Press release, NanoString Technologies, DEC 7, 2015, View Source [SID:1234508451]). The presentations include:

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Multiple decision impact studies demonstrating Prosigna’s influence on adjuvant therapy selection by physicians
A study by the Danish Breast Cancer Group validating previous observations that the Prosigna risk of recurrence score can predict the probability of loco-regional recurrence

Studies evaluating the ability of Prosigna/PAM50 to predict response to various therapies in the neoadjuvant and metastatic setting
A study describing the differences in intrinsic subtype distribution between patients of African descent and Caucasian descent
A description of the ongoing OPTIMA clinical trial, describing the prospective evaluation of Prosigna as a test to identify node-positive breast cancer patients who may be spared adjuvant chemotherapy

Following are details for the Prosigna/PAM50 posters to be presented (all times shown are Central Standard Time):

Thursday, December 10

Session #: Poster Session 2, P2-08-10
Abstract Title: Validation of prediction of local recurrence (LR) by Prosigna (PAM50) in a Danish breast cancer cooperative group (DBCG) cohort of hormone receptor positive (HR+), postmenopausal early breast cancer (EBC) patients allocated to 5yr of endocrine therapy (ET)
Location: Halls A-B
Time: 7:30AM – 9:00AM

Session #: Poster Session 2, P2-08-16
Abstract Title: Prognostic and predictive abilities of intrinsic subtype in hormone receptor-positive metastatic breast cancer from the EGF30008 phase III clinical trial
Location: Halls A-B
Time: 7:30AM – 9:00AM

Session #: Poster Session 3, P3-07-14
Abstract Title: Prosigna intrinsic subtyping predicts response to neoadjuvant combination therapy in study that includes herceptin within HER2+ (IHC) patients
Location: Halls A-B
Time: 5:00PM – 7:00PM

Session #: Poster Session 3, P3-07-15
Abstract Title: Prosigna subtype correlation is a strong predictor of response to neoadjuvant chemotherapy (NAC) in early breast cancer (EBC) study
Location: Halls A-B
Time: 5:00PM – 7:00PM

Session #: Poster Session 3, P3-07-42
Abstract Title: Predicting outcome and benefit to first-line bevacizumab in advanced/metastatic hormone receptor (HR)+/HER2-negative breast cancer (BC) treated with endocrine therapy: A correlative science study from the LEA phase III clinical trial (GEICAM/2006-11_GBG 051)
Location: Halls A-B
Time: 5:00PM – 7:00PM

Session #: Poster Session 3, P3-07-66
Abstract Title: Efficacy and gene expression results from eribulin SOLTI1007 neoadjuvant study
Location: Halls A-B
Time: 5:00PM – 7:00PM

Session #: Poster Session OT2, OT2-03-02
Abstract Title: DI study: Decision impact of the NanoString Technologies Prosigna in early breast cancers
Location: Halls A-B
Time: 5:00PM – 7:00PM

Friday, December 11

Session #: Poster Session 5, P5-07-03
Abstract Title: Prosigna results impact on adjuvant decision making in early breast cancer (EBC): Final analysis of the prospective WSG study
Location: Halls A-B
Time: 5:00PM – 7:00PM

Session #: Poster Session OT3, OT3-02-12
Abstract Title: OPTIMA (optimal personalised treatment of early breast cancer using multi-parameter analysis), a prospective trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions
Location: Halls A-B
Time: 5:00PM – 7:00PM

Saturday, December 12

Session #: Poster Session 6, P6-04-05
Abstract Title: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data
Location: Hall C
Time: 7:30AM – 9:00AM

Session #: Poster Session 6, P6-05-02
Abstract Title: Intrinsic subtype and gene expression changes between primary and metastatic breast cancer
Location: Hall C
Time: 7:30AM – 9:00AM
About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma. The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as: (1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

On December 7, 2015 Seattle Genetics, Inc. (Nasdaq: SGEN) reported several data presentations at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Orlando, Florida, December 5-8, 2015, evaluating ADCETRIS (brentuximab vedotin) as both monotherapy and combination therapy in multiple Hodgkin lymphoma (HL) disease settings (Press release, Seattle Genetics, DEC 7, 2015, View Source;p=RssLanding&cat=news&id=2120636 [SID:1234508471]). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS is being evaluated globally as the foundation of therapy for HL in more than 45 ongoing clinical trials, including trials led by Seattle Genetics and its development and commercialization partner, Takeda, as well as by independent investigators.

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"For the past decade, we have been committed to improving the therapeutic options for HL patients, and we have made tremendous progress with ADCETRIS, which is now FDA-approved for two HL indications and is being evaluated broadly in multiple settings and combinations across more than 45 ongoing clinical trials," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "The data presented at the ASH (Free ASH Whitepaper) annual meeting continue to support our goal to establish ADCETRIS as the foundation of care for HL. Notably, final results from the pivotal HL clinical trial demonstrate that some patients remain free from recurrence after more than five years of follow-up. We continue to explore novel ADCETRIS combinations in the salvage setting and in older frontline HL patients, with data from ongoing phase 1/2 and phase 2 clinical trials demonstrating objective response rates greater than 90 percent, supporting further follow-up and evaluation of therapeutic strategies."

ADCETRIS is currently not approved for the treatment of frontline HL or as combination therapy for HL.

Five-Year Survival Data Demonstrating Durable Responses from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #2736, poster presentation on Sunday, December 6, 2015)

A pivotal, single-arm trial, which supported the FDA approval in 2011 of ADCETRIS for this indication, was conducted in 102 relapsed or refractory HL patients who had previously received an autologous stem cell transplant (ASCT) to assess the efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival and overall survival. Enrolled patients had received a median of more than three prior chemotherapy regimens. After a five-year follow-up period, the final results from the pivotal trial include:

The estimated median overall survival was 40.5 months (95% confidence interval [CI]: 28.7, 61.9 [range, 1.8 to 72.9+ mos]). The estimated five-year survival rate was 41 percent.

Of the 102 patients treated, 15 remained in remission per investigator assessment with a median observation time of 69.5 months (range, 66.5–72.9 months) and may potentially be cured. Of these patients, nine received no further therapy and six received consolidative allogeneic stem cell transplant.

Of the 34 patients who had a complete remission, the median overall survival and progression-free survival had not yet been reached.

Overall, patients received a median of nine cycles of ADCETRIS treatment and patients who achieved a complete remission received a median of 13.5 cycles of therapy.

The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia and diarrhea. Treatment emergent peripheral neuropathy was experienced by 56 patients (55 percent). Eighty-eight percent of these patients experienced improvement of their peripheral neuropathy symptoms, including 73 percent with complete resolution.

The most common Grade 3 or higher adverse events occurring in at least five percent of patients were neutropenia (20 percent); peripheral sensory neuropathy and thrombocytopenia (eight percent each); and anemia (six percent)
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Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse (Abstract #3172, poster presentation on Sunday, December 6, 2015)

The phase 3 AETHERA clinical trial was designed to evaluate the potential of single-agent ADCETRIS to extend progression-free survival post-ASCT in patients with classical HL who were at high risk of relapse or progression. Patients received ADCETRIS or placebo every three weeks for up to approximately one year (16 cycles). A total of 329 HL patients were enrolled, including 165 on the ADCETRIS arm and 164 on the placebo arm. Based on these trial results, ADCETRIS was approved by the FDA in August 2015 for the treatment of patients with classical HL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation. Updated three-year follow-up efficacy and safety data include:

The three-year progression-free survival rate per investigator was 61 percent in the ADCETRIS arm compared to 43 percent in the placebo arm. Median progression-free survival per investigator was not yet reached in the ADCETRIS arm versus 15.8 months in the placebo arm. The hazard ratio was 0.52 favoring the ADCETRIS arm.

A progression-free survival analysis evaluating subgroups, including the number of risk factors, initial response to salvage therapy and disease characteristics, showed patients with more risk factors for relapse post-ASCT appeared to have the greatest benefit from ADCETRIS consolidation therapy.

Among patients on the ADCETRIS arm who did not experience disease progression on therapy, progression-free survival rates were higher in patients who remained on therapy longer.

In the ADCETRIS arm, 112 patients (67 percent) reported peripheral neuropathy. To date, 88 percent of these patients had resolution or improvement in symptoms, with 66 percent having complete resolution.

Patients remain in long-term follow-up. Final overall survival analysis is planned for 2020.

Brentuximab Vedotin in Combination with Dacarbazine or Bendamustine for Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Multi-Cohort Phase 2 Study (Abstract #587, oral presentation on Monday, December 7, 2015 at 11:30 a.m. ET)

Interim results were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with dacarbazine or bendamustine (Treanda) as frontline therapy for HL patients age 60 years or older. ADCETRIS combination data were reported from 22 patients treated with dacarbazine and 20 patients treated with bendamustine. The median age of patients was 69 years in the dacarbazine combination arm and 75 years in the bendamustine combination arm. At least 70 percent of patients in each arm had stage III/IV disease at the time of diagnosis and the majority were frail with multiple comorbidities. The data will be highlighted in an oral presentation by Christopher Yasenchak, M.D., Willamette Valley Cancer Institute and Research Center/US Oncology Research.

Combination data evaluating ADCETRIS and dacarbazine or bendamustine include:

Of 21 evaluable patients in the dacarbazine combination arm, all patients (100 percent) had an objective response, including 14 patients (67 percent) with a complete remission and seven patients (33 percent) with a partial remission.

Of 16 evaluable patients in the bendamustine combination arm, all patients (100 percent) had an objective response, including 13 patients (81 percent) with a complete remission and three patients (19 percent) with a partial remission.

In the dacarbazine combination arm, the median observation time was 13.4 months and progression-free survival at six months was 95 percent, at nine months was 89 percent and 12 months was 66 percent. In the bendamustine combination arm the median observation time was too short to provide a reliable progression-free survival estimate.

The most common adverse events of any grade occurring in at least 25 percent of patients in the dacarbazine combination arm were peripheral sensory neuropathy (77 percent); constipation (45 percent); fatigue and nausea (41 percent each) and joint pain and peripheral edema (32 percent each).

The most common adverse events of any grade occurring in at least 25 percent of patients in the bendamustine combination arm were diarrhea (75 percent); nausea (60 percent); fatigue (55 percent) and decreased appetite and fever (40 percent each). Two patient deaths considered unrelated to treatment occurred within 30 days of last dose of study drug. Enrollment on the bendamustine arm was closed given the tolerability of the combination did not meet study goals for this fragile patient population. Patients in this arm continued to receive treatment with single-agent ADCETRIS.

Brentuximab Vedotin Plus Bendamustine: A Highly Active Salvage Treatment Regimen for Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #3982, poster presentation on Monday, December 7, 2015)

Updated data were presented from an ongoing phase 1/2 single-arm, open-label clinical trial evaluating the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients who had relapsed or were refractory to frontline therapy. The combination therapy was administered every three weeks, for up to six cycles, followed by additional treatment with single-agent ADCETRIS for up to a total of 16 cycles of therapy. After patients have received at least two cycles of combination therapy, they have the option to pause treatment to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Current treatment options in this setting include salvage chemotherapy regimens that historically have resulted in variable complete remission rates of 19 to 60 percent and are associated with significant toxicities.

Data were reported from 55 patients with a median age of 36 years. The majority of patients (53 percent) had stage III/IV disease at the time of initial diagnosis, with 28 primary refractory patients (51 percent) and 27 relapsed patients (49 percent) after frontline therapy, primarily consisting of the chemotherapy regimen ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine). Updated data from this phase 1/2 trial include:

Of the 53 evaluable patients, 49 patients (93 percent) had an objective response to combination therapy with brentuximab vedotin plus bendamustine, including 40 patients (76 percent) with a best response of complete remission and nine patients (17 percent) with a best response of partial remission. The complete remission rate was 88 percent in relapsed patients and 64 percent in primary refractory patients.

The median overall survival for all 53 patients, including the 40 patients who received an ASCT, had not yet been reached.
The estimated 18-month progression-free survival rate was 75 percent for the 53 evaluable patients and 83 percent for the 40 patients who proceeded to ASCT.

For patients who achieved a complete remission during combination therapy, the percentage of progression events was similar whether patients did or did not have an ASCT (21 percent versus 17 percent, respectively).

Patients who did not receive ADCETRIS consolidation treatment experienced a higher proportion of progression-free survival events compared to those who received consolidation therapy (29 percent versus 15 percent).

The most common adverse events from combination treatment were infusion-related reactions (IRRs) which were seen in 58 percent of patients. The most common symptoms associated with IRRs occurring in more than 15 percent of patients were fever, chills, dyspnea, flushing and nausea. The trial protocol was amended to require premedication with corticosteroids and antihistamines, which decreased the severity of IRRs.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including the phase 3 ALCANZA trial and two additional phase 3 studies, ECHELON-1 in frontline classical HL and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in more than 55 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.