On August 31, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that the United States Adopted Names (USAN) Council and the International Nonproprietary Names (INN) Expert Group have approved the nonproprietary name "tucatinib" for ONT-380, the Company’s lead product candidate for the treatment of advanced, metastatic HER2+ breast cancer (Press release, Cascadian Therapeutics, AUG 31, 2016, View Source [SID:1234514839]).

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"We’re pleased to adopt the new nonproprietary name tucatinib for our lead product candidate, ONT-380," said Scott Myers, President and CEO of Cascadian Therapeutics. "Tucatinib has shown promising systemic activity, encouraging activity against brain metastases, and a favorable safety profile in patients with advanced HER2+ breast cancer. We continue to enroll our Phase 2 combination trial, HER2CLIMB, and plan to report new data from our ongoing Phase 1b ‘Triplet’ study of tucatinib in combination with capecitabine and trastuzumab later this year."

The USAN Council and the World Health Organization’s INN Expert Group select simple, informative and unique nonproprietary names for drugs based on pharmacological and/or chemical relationships to allow for clear identification and communication among health professionals.

On August 31, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that its global non-interventional, observational multiple myeloma study is now enrolling patients (Press release, Takeda, AUG 31, 2016, View Source [SID:1234514832]). Titled INSIGHT-MM, the study aims to enroll 5,000 patients over three years with a goal of following each patient for a minimum of five years in an effort to track patterns in disease presentation, patient characteristics, treatment and outcomes and thereby enhance the understanding of real world experience of patients with multiple myeloma.

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"As both a physician and a patient, I have seen – and experienced – rapid changes in the approach to multiple myeloma treatment. Even with the recent introduction of new therapies, more work needs to be done to improve outcomes for patients across the globe," said Jim Omel, M.D., INSIGHT-MM Steering Committee member, who was diagnosed with multiple myeloma in 1997. "The INSIGHT-MM study gives the community an opportunity to work together to better understand how clinical advances affect multiple myeloma patients in the real world."

"In relatively rare diseases, such as multiple myeloma, we often lack access to large datasets that can help inform decisions in our practices," said Faith Davies, M.D., Professor of Medicine and Medical Director, Myeloma Institute, University of Arkansas for Medical Sciences, INSIGHT-MM Steering Committee Co-Chair. "By gathering comprehensive real world data on this scale, we will have the opportunity to identify best practices from across the globe to help us better understand what works and what doesn’t for specific patients. These learnings can in turn enhance our efforts to improve disease management for people living with multiple myeloma."

Study sites at the University of Arkansas for Medical Sciences; the University of California, San Diego; and the University of Cincinnati Cancer Institute – the first three of an anticipated more than 150 global locations – are now active and have enrolled the first patients in the study. Led by an international steering committee of myeloma experts, the INSIGHT-MM study will gather data via routine office visits, medical records and patient self-reported outcomes. Participation in INSIGHT-MM, a non-interventional study, will not determine or alter patients’ treatment; rather, patients will receive their usual therapy as determined by their healthcare provider during the course of their care. Designed to be collaborative, INSIGHT-MM remains open for the multiple myeloma community to propose analyses and request data that has been collected during the study.

"At Takeda Oncology, we have worked with the multiple myeloma community for the benefit of patients for nearly two decades. Given the increased complexity of treatment in recent years, we saw the need to understand treatment patterns and patients’ experiences around the world," said Liviu Niculescu, Vice President Global and U.S. Medical Affairs, Takeda Oncology. "With patients and multiple myeloma experts, we designed the innovative INSIGHT-MM trial to be an open source of data – large enough to reveal differences and trends globally. We invite collaborations from other similar studies in order to increase the size of available databases and move us closer to a future when robust data on multiple myeloma enables us to change the face of the disease."

The INSIGHT-MM study is currently enrolling patients in the United States and will soon be enrolling patients globally. The following countries are participating in the INSIGHT-MM study: The United States, the United Kingdom, Germany, Italy, Spain, Brazil, Israel, France, Belgium, Greece, Mexico, China, Taiwan, Colombia and Turkey. To learn more, please visit View Source

About Multiple Myeloma

Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of monoclonal plasma cells, or myeloma cells, becomes cancerous and multiplies. These malignant plasma cells have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer, with approximately 30,000 new cases in the US, 39,000 new cases in the EU and 114,000 new cases globally per year.

On August 31, 2016 Pfizer Inc. (NYSE:PFE) reported that the European Commission has approved XALKORI (crizotinib) for the treatment of adults with ROS1-positive advanced non-small cell lung cancer (NSCLC) (Press release, Pfizer, AUG 31, 2016, View Source [SID:1234514820]).

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In the European Union (EU), XALKORI is also indicated for treatment of adults with anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. In March of this year, XALKORI was approved by the United States (U.S.) Food and Drug Administration for patients with metastatic NSCLC whose tumors are ROS1-positive. With this approval, XALKORI becomes the only biomarker-driven therapy approved for patients with either ALK positive or ROS1-positive advanced NSCLC in the EU and U.S

"The European Commission’s decision to approve XALKORI for ROS1-positive advanced NSCLC represents an important milestone for patients who previously had limited treatment options," said Andreas Penk, MD, Regional President, International Developed Markets, Pfizer Oncology. "We now know that NSCLC is not a single disease, but includes a number of molecularly defined tumors with different clinical characteristics and treatment options. With EU approvals in two distinct molecular targets in advanced NSCLC, ROS1 and ALK, XALKORI continues to break new ground and exemplify our commitment to precision drug development and patients."

The European Commission’s approval of XALKORI in patients with ROS1-positive advanced NSCLC follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine’s Agency, and is supported by compelling results from a multicenter, single-arm Phase 1 study (Study 1001) that included patients with ROS1-positive advanced NSCLC treated with 250 mg of XALKORI orally twice daily.

The efficacy outcome measure in this study was objective response rate (ORR) by RECIST. Secondary endpoints included time to tumor response (TTR), duration of response (DOR) and progression-free survival (PFS). Tumors were tested for ROS1 rearrangements by laboratory-developed break-apart fluorescence in situ hybridization (FISH) (96%) or real-time polymerase chain reaction (RT-PCR) (4%) assay.1

The results of this study showed that XALKORI exhibited marked anti-tumor activity in patients with ROS1-positive advanced NSCLC and met its primary endpoint of ORR. Additionally, the safety profile of XALKORI in ROS1-positive advanced NSCLC was generally consistent with that observed in patients with ALK-positive advanced NSCLC.1 The updated data set used to support this approval will be presented at a future medical meeting.

XALKORI is widely recognized as a first-line standard of care for patients with ALK-positive advanced NSCLC. XALKORI was the first ALK inhibitor approved by regulatory authorities in the U.S., EU, China and Japan, and it is now approved in nearly 90 countries. To date, more than 25,000 patients have been treated with XALKORI worldwide.2

ROS1 rearrangements occur when the ROS1 gene attaches to another gene and changes the way each gene normally functions, which can contribute to cancer-cell growth. Epidemiology data suggest that ROS1 rearrangements occur in approximately one percent of NSCLC cases.3 Of the estimated 1.5 million new cases of NSCLC worldwide each year, roughly 15,000 may be driven by oncogenic ROS1 fusions.2,4,5

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is the leading cause of cancer death in both men and women.6 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.7 Approximately 57 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent.8

XALKORI (crizotinib) Indications and Important Safety Information (as per U.S. Prescribing Information)

XALKORI is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. XALKORI is also indicated for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive.

Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of patients treated with XALKORI across clinical trials (n=1719). Transaminase elevations generally occurred within the first 2 months. Monitor with liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 2 months of treatment, then once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Permanently discontinue for ALT/AST elevation >3 times ULN with concurrent total bilirubin elevation >1.5 times ULN (in the absence of cholestasis or hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI as indicated.

Interstitial Lung Disease (Pneumonitis): Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9% of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4, and 0.5% had fatal ILD. ILD generally occurred within 3 months after initiation of treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes and permanently discontinue XALKORI in patients with drug-related ILD/pneumonitis.

QT Interval Prolongation: QTc prolongation can occur. Across clinical trials (n=1616), 2.1% of patients had QTcF (corrected QT by the Fridericia method) ≥500 ms and 5.0% had an increase from baseline QTcF ≥60 ms by automated machine-read evaluation of ECGs. Avoid use in patients with congenital long QT syndrome. Monitor with ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia. Withhold XALKORI in patients who develop QTc >500 ms on at least 2 separate ECGs until recovery to a QTc ≤480 ms, then resume at a reduced dose.

Bradycardia: Symptomatic bradycardia can occur. Across clinical trials, bradycardia occurred in 12.7% of patients treated with XALKORI (n=1719). Avoid use in combination with other agents known to cause bradycardia. Monitor heart rate and blood pressure regularly. In cases of symptomatic bradycardia that is not life-threatening, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, re-evaluate the use of concomitant medications, and adjust the dose of XALKORI. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring.

Severe Visual Loss: Across clinical trials, the incidence of Grade 4 visual field defect with vision loss was 0.2% (n=1719). Discontinue XALKORI in patients with new onset of severe visual loss (best corrected vision less than 20/200 in one or both eyes). Perform an ophthalmological evaluation. There is insufficient information to characterize the risks of resumption of XALKORI in patients with a severe visual loss; a decision to resume should consider the potential benefits to the patient.

Vision Disorders: Most commonly visual impairment, photopsia, blurred vision or vitreous floaters, occurred in 63.1% of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had Grade 4 visual impairment. The majority of patients on the XALKORI arms in Studies 1 and 2 (>50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact on daily activities.

Embryo-Fetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 45 days (females) or 90 days (males) respectively, following the final dose of XALKORI.

ROS1-positive Metastatic NSCLC: Safety was evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study, and was generally consistent with the safety profile of XALKORI evaluated in patients with ALK-positive metastatic NSCLC. Vision disorders occurred in 92% of patients in the ROS1 study; 90% of patients had Grade 1 vision disorders and 2% had Grade 2.

Adverse Reactions: Safety was evaluated in a phase 3 study in previously untreated patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169). Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% of patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis. Common adverse reactions (all grades) occurring in ≥25% and more commonly (≥5%) in patients treated with XALKORI vs chemotherapy were vision disorder (71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting (46% vs 36%), constipation (43% vs 30%), upper respiratory infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain (26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher incidence with XALKORI vs chemotherapy were QT prolongation (2% vs 0%), and constipation (2% vs 0%). In patients treated with XALKORI vs chemotherapy, the following occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea (56%), decreased appetite (30%), fatigue (29%), and neuropathy (21%) also occurred in patients taking XALKORI.

Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Avoid concomitant use of CYP3A substrates with narrow therapeutic range in patients taking XALKORI. If concomitant use of CYP3A substrates with narrow therapeutic range is required in patients taking XALKORI, dose reductions of the CYP3A substrates may be required due to adverse reactions.

Lactation: Because of the potential for adverse reactions in breastfed infants, advise females not to breast feed during treatment with XALKORI and for 45 days after the final dose.

Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations. Use caution in patients with hepatic impairment.

Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment.

For more information and full Prescribing Information, visit www.XALKORI.com (link is external).

On August 31, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that the U.S. Food and Drug Administration (FDA) has approved an investigational device exemption (IDE) for its RNA-based companion diagnostic, next-generation sequencing (NGS) assay (Trailblaze Pharos) (Press release, Ignyta, AUG 31, 2016, View Source [SID:1234514819]). The Trailblaze Pharos assay is intended for use in identifying patients, including those who are treatment-naïve, who have solid tumors with NTRK1/2/3, ROS1, or ALK gene rearrangements leading to fusion proteins, to determine eligibility for enrollment into the global STARTRK-2 trial, a Phase 2 study of entrectinib, a novel, orally available, CNS-penetrant tyrosine kinase inhibitor targeting tumors that harbor NTRK1/2/3 (encoding TrkA/TrkB/TrkC), ROS1, or ALK gene fusions.

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"We are pleased to have been granted this IDE approval for our investigational companion diagnostic assay, as it allows us to screen potential patients for STARTRK-2 who might not otherwise have access to tumor profiling for these fusions and therefore may never have been identified," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We look forward to continuing to work with the FDA on developing and providing a robust assay to help physicians identify cancer patients who may be eligible for our clinical studies."

An IDE allows an investigational device, in this case the Trailblaze Pharos assay, to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application submission to FDA. An IDE application is approved only after direct review by the FDA on many aspects of the device validation and how clinical testing will be performed.

About Trailblaze Pharos

The Trailblaze Pharos assay for NTRK1/2/3, ROS1, and ALK gene rearrangements is a next-generation sequencing (NGS) based assay for the qualitative detection of fusions in the NTRK1/2/3, ROS1, or ALK genes in the RNA from formalin-fixed paraffin-embedded (FFPE) human solid tumor tissue. The assay is intended to be used as an aid in selecting patients, including those who are treatment-naïve, with solid tumors that harbor a gene rearrangement in NTRK1/2/3, ROS1, or ALK, for whom enrollment in the STARTRK-2 study may be appropriate. A laboratory developed test (LDT) version of the Trailblaze Pharos assay was previously used to identify non-treatment-naïve patients with NTRK1/2/3, ROS1, or ALK gene rearrangements who might be eligible for the STARTRK-2 study.

About Entrectinib

Entrectinib is a novel, orally available, selective tyrosine kinase inhibitor targeting tumors that harbor activating alterations to NTRK1/2/3 (encoding TrkA/TrkB/TrkC), ROS1, or ALK. Entrectinib is the most potent Trk inhibitor in the clinic, without undesirable off-target activity, and the only Trk inhibitor with clinically demonstrated activity against primary and metastatic CNS disease. This product candidate is in a Phase 2 clinical trial called STARTRK-2, which is the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.

On August 31, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental Biologics License Application (sBLA) for the use of ofatumumab (Arzerra) in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) (Press release, Genmab, AUG 31, 2016, View Source [SID:1234514818]). The application, which received Priority Review in May 2016, was submitted to the FDA by Novartis under the ofatumumab collaboration between Novartis and Genmab.

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Approval for this indication by the FDA is based on results from the Phase III COMPLEMENT 2 study that evaluated ofatumumab in combination with FC versus FC alone in patients with relapsed CLL. Top-line results from COMPLEMENT 2 were reported in April 2015.

"This is the fourth CLL indication approved in the U.S. for Arzerra, and we are pleased to see the availability of this treatment expand to a wider number of patients," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About CLL
CLL is the most commonly diagnosed adult leukemia in Western countries, and accounts for approximately 1 in 4 cases of leukemia.1 Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment.2

About COMPLEMENT 2
COMPLEMENT 2 (NCT00824265) is an open-label, two-arm, randomized, Phase III study, which included 365 patients in 18 countries with relapsed CLL. Patients in the study were randomized 1:1 to treatment with up to six cycles of ofatumumab in combination with fludarabine and cyclophosphamide (FC) or up to six cycles with fludarabine and cyclophosphamide alone.
The primary endpoint of the study was progression free survival (PFS), which was assessed by an Independent Review Committee (IRC) according to the International Workshop for Chronic Lymphocytic Leukaemia (iwCLL) updated 2008 National Cancer Institute-sponsored Working Group (NCIWG) guidelines.3 The study met the primary endpoint with a median progression free survival in patients receiving ofatumumab in combination with FC of 28.9 months, compared to 18.8 months in patients receiving FC alone (HR =0.67, p=0.0032). Secondary endpoints included overall response rate, overall survival, patient reported outcomes, time to response, duration of response, time to progression, time to next therapy, safety assessments and quality of life. The safety profile observed in this study was consistent with other trials of ofatumumab and no new safety signals were observed.

About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.

In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate and for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).
Arzerra is marketed under a collaboration agreement between Genmab and Novartis. Novartis has rights to develop ofatumumab in autoimmune indications, including multiple sclerosis.