News Article | December 7, 2016
Updated Data from Phase 1b Triplet Combination Trial at SABCS; Increased Median PFS to 7.8 Months and ORR to 61 Percent; Median Duration of Response (MDR) at 10 Months in Third-line Setting for Patients With and Without Brain Metastases HER2CLIMB Amended to Single Pivotal Randomized Trial to Assess Progression-Free Survival (PFS) as Primary Endpoint SAN ANTONIO, Texas, Dec. 07, 2016 (GLOBE NEWSWIRE) -- Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, today announced that following a recent meeting with the U.S. Food and Drug Administration (FDA) and discussions with the Company’s external Steering Committee, it has amended the HER2CLIMB Phase 2 clinical trial of tucatinib (also known as ONT-380) by increasing the sample size so that, if successful, the trial could serve as a single pivotal study to support registration. This decision is supported by the most recent data from the Company’s ongoing Phase 1b study evaluating the same “triplet combination” therapy being investigated in the amended Phase 2 trial, which is tucatinib in combination with capecitabine and trastuzumab for patients with metastatic or locally advanced HER2-positive breast cancer, including patients with and without brain metastases. Tucatinib is an oral, small molecule kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. HER2CLIMB is an ongoing randomized, controlled pivotal trial evaluating tucatinib in combination with trastuzumab (Herceptin®) and capecitabine (Xeloda®) in heavily pre-treated patients with advanced HER2-positive breast cancer with or without brain metastases. “We are extremely pleased with the outcome of our recent interactions with the FDA, and we have decided to amend the current Phase 2 clinical trial of tucatinib so that, if successful, HER2CLIMB could serve as a single pivotal registration trial and potentially provide us with a more efficient path to market,” commented Scott Myers, President and CEO of Cascadian Therapeutics. “We look forward to continuing a collaborative relationship with the agency and our clinical investigators as we advance the development of tucatinib in combination in the third-line metastatic breast cancer setting where there is no single standard-of-care and a need for more tolerable therapeutic options. The improvement in the updated data from our Phase 1b “triplet combination” study reinforces our strategy with tucatinib in this patient population.” Updated Phase 1b trial results for the triplet combination show that the combination (tucatinib with capecitabine and trastuzumab) continues to be well tolerated, with the updated median progression-free survival (PFS) increasing to 7.8 months, an overall response rate (ORR) of 61 percent and a median duration of response (MDR) of 10 months. Patients in the Phase 1b triplet combination previously received a median of 3 HER2-targeted agents, such as trastuzumab, pertuzumab, lapatinib or T-DM1. Poster presentations on the amended HER2CLIMB pivotal trial and the updated Phase 1b “triplet combination” trial data will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS), December 6-10, 2016. “The more mature dataset from the Phase 1b trial continues to show tucatinib may be combined with other current targeted therapies to achieve durable responses in patients who have received multiple prior lines of therapy,” said Erika Hamilton, M.D., Director of Breast and Gynecology Cancer Research at Sarah Cannon Research Institute. “Tucatinib in combination appears to be well-tolerated, potentially making it a highly desirable HER2 therapy for a patient population that vitally needs new options. An active agent showing systemic activity, with a tolerable safety profile and early signs of activity in HER2-positive brain metastases, would represent a meaningful advancement in treating metastatic breast cancer.” HER2CLIMB is a randomized (2:1), double-blind, controlled pivotal clinical trial comparing tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab and T-DM1. Following a meeting with the FDA, the primary endpoint remains PFS based upon independent radiologic review, and the sample size will increase to approximately 480 patients, including patients already enrolled in the trial. Key objectives related to assessing activity in brain metastases include a key secondary endpoint of PFS in a subset of patients with brain metastases. All patients will be followed for overall survival. HER2CLIMB is currently enrolling in the United States and Canada and is expected to expand into Europe, Australia and Israel. Details of the amended HER2CLIMB clinical trial design will be presented in a poster session (OT1-02-09) at SABCS on Wednesday, December 7, 2016 beginning at 5:00 p.m. CST. Results reported in June 2016 showed a median PFS of 6.3 months and ORR of 58 percent. Updated data from the SABCS poster (P4-21-01) of the Phase 1b study show encouraging safety and anti-tumor activity in patients with and without brain metastases, with an updated median PFS of 7.8 months (a 24 percent improvement over prior median PFS), ORR of 61 percent and a median duration of response of 10 months. Patients with and without brain metastases had similar response rate. The combination of tucatinib with trastuzumab and capecitabine was well-tolerated. Most treatment-emergent adverse events were Grade 1, with few tucatinib dose reductions and no required prophylactic use of antidiarrheal agents. Updated results will be presented in a poster session at SABCS on Friday, December 9, 2016 beginning at 7:30 a.m. CST. Tucatinib is an orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 directed agents such as trastuzumab.1 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, ovarian and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tumors that overexpress HER2 are more aggressive and historically have been associated with poor overall survival, compared with HER2-negative cancers. Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. The American Cancer Society estimates that 20-25 percent of the approximately 234,000 annual breast cancer diagnoses in the U.S. are HER2-positive. Historically, HER2 disease has been associated with shorter survival times as well as a higher risk of recurrence and CNS disease (brain metastases). Approximately 30 to 50 percent of HER2-positive breast cancer patients develop brain metastases over time.2,3 Over the past two decades, the approvals of four targeted treatments (trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine) have led to improved time to progression and survival rates of HER2-positive patients. Despite these advances, there is still a significant need for new therapies that can impact metastatic disease, including brain metastases, and be tolerated for longer periods of time. Cascadian Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative product candidates for the treatment of cancer. The lead product candidate, tucatinib (also known as ONT-380) is an oral, selective small molecule HER2 inhibitor. Cascadian Therapeutics is conducting a randomized, double-blind, placebo-controlled pivotal clinical trial called HER2CLIMB, which is evaluating tucatinib versus placebo in combination with capecitabine and trastuzumab in late stage HER2-positive breast cancer patients, with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and T-DM1. Additional details on HER2CLIMB can be found at www.clinicaltrials.gov (Identifier: NCT02614794) or www.HER2CLIMB.com. For more information, please visit www.cascadianrx.com. In order to provide Cascadian Therapeutics' investors with an understanding of its current results and future prospects, this release contains statements that are forward-looking. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include Cascadian Therapeutics' expectations regarding clinical development activities, and the potential benefits of tucatinib. Forward-looking statements involve risks and uncertainties related to Cascadian Therapeutics' business and the general economic environment, many of which are beyond its control. These risks, uncertainties and other factors could cause Cascadian Therapeutics' actual results to differ materially from those projected in forward-looking statements, including the risks associated with the costs and expenses of developing its product candidates, the adequacy of financing and cash, cash equivalents and investments, changes in general accounting policies, general economic factors, achievement of the results it anticipates from its preclinical development and clinical trials of its product candidates and its ability to adequately obtain and protect its intellectual property rights. Although Cascadian Therapeutics believes that the forward-looking statements contained herein are reasonable, it can give no assurance that its expectations are correct. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For a detailed description of Cascadian Therapeutics' risks and uncertainties, you are encouraged to review the documents filed with the securities regulators in the United States on EDGAR and in Canada on SEDAR. Except as required by law, Cascadian Therapeutics does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof. All trademarks are the property of their respective owners. References: 1. Koch et al. American Association of Clinical Research (AACR) 2011. 2. Metro et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine, Annals of Oncology, vol. 212, no. 3, pp. 625-630, 2011. 3. DOI: 10.1200/JCO.2013.54.0955 Journal of Clinical Oncology32, no. 19 (July 2014) 2100-2108.
News Article | December 12, 2016
– Company to Host Investor Conference Call and Webcast on Monday, December 19, 2016 – STAMFORD, Conn., Dec. 12, 2016 (GLOBE NEWSWIRE) -- Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, today announced that the abstract titled "Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions" has been accepted for oral presentation at the European Society for Medical Oncology (ESMO) Asia Congress, taking place December 16-19, 2016 in Singapore. Data from this trial were last presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2016. The presentation will include an efficacy and durability update for enrolled patients with TRK fusions. The schedule for the presentation is as follows: Presentation Session Date & Time: December 18, 2016, 4:30 p.m. to 6:00 p.m. SGT Title: Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions Abstract Number: 150O Session: Developmental Therapeutics, Proffered Paper Session (oral presentation) Presenter: Todd Bauer, M.D., Associate Director, Drug Development; Principal Investigator, Sarah Cannon Research Institute Conference Call and Webcast In conjunction with ESMO Asia, Loxo Oncology will be hosting a conference call and live webcast with slides and Q&A on December 19, 2016 at 8:00 a.m. ET to discuss the LOXO-101 Phase 1 data and provide a comprehensive program and pipeline update. The company anticipates that the conference call and webcast will last 60-90 minutes. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 16640119. A live webcast of the presentation will be available at http://ir.loxooncology.com/. A replay of the webcast will be available shortly after the conclusion of the call and archived on the company's website for 30 days following the call. About Loxo Oncology Loxo Oncology is a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers. Our pipeline focuses on cancers that are uniquely dependent on single gene abnormalities, such that a single drug has the potential to treat the cancer with dramatic effect. We believe that the most selective, purpose-built medicines have the highest probability of maximally inhibiting the intended target, thereby delivering best-in-class disease control and safety. Our management team seeks out experienced industry partners, world-class scientific advisors and innovative clinical-regulatory approaches to deliver new cancer therapies to patients as quickly and efficiently as possible. For more information, please visit the company's website at www.loxooncology.com.
News Article | December 12, 2016
WOBURN, Mass.--(BUSINESS WIRE)--Sirtex Medical Limited (ASX: SRX) today announced that SIR-Spheres® Y-90 resin microspheres has been included as a Category 2A recommended treatment in the latest National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for colon cancer and rectal cancer. This designation denotes that there is uniform consensus among the NCCN panel that Selective Internal Radiation Therapy (SIRT) with yttrium-90 microspheres is an appropriate option in patients with liver dominant, chemotherapy resistant colorectal disease (mCRC). This recommendation places SIR-Spheres Y-90 resin microspheres at the same designation as the recommended mCRC systemic chemotherapeutic regimens. The new NCCN Guidelines are available online at https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Nearly 140,000 Americans are diagnosed with colorectal cancer every year1, more than 50 percent of whom will see the cancer spread to their liver.2 “The NCCN Guidelines aim to assist medical teams, patients and their families in making informed treatment-related decisions with the goal of optimal cancer care,” said Kevin Richardson, chief executive officer for Sirtex Americas. “The 2A designation represents a very important milestone for SIR-Spheres resin microspheres and provides further validation for the role of our medical device as an important treatment option for unresectable, liver dominant metastatic colorectal cancer. We also have positive signals in the first-line setting through the results to date of the pivotal SIRFLOX study3 and eagerly anticipate the overall survival results in more than 1,100 patients from the SIRFLOX, FOXFIRE and FOXFIRE Global studies which we expect to be available in the first half of 2017.” These findings are also supported by the landmark MORE study4, a large retrospective analysis conducted in the United States with SIR-Spheres Y-90 resin microspheres in more than 600 mCRC patients. The MORE study helped to increase the understanding of SIRT as a treatment option for patients who have failed multiple lines of chemotherapy while highlighting the positive aspects of the safety and efficacy of the protocol for patients of all ages. “Clinical research has shown that SIRT brings patients with colorectal liver metastases improved and prolonged quality of life,” said lead investigator of the MORE study, Andrew S. Kennedy, M.D., F.A.C.R.O., director, Radiation Oncology Research at Sarah Cannon Research Institute, Nashville, Tenn. “We look forward to expanding access to this outpatient procedure, which has demonstrated minimal side effects, to improve outcomes for this population of patients and advance the standard of care.” SIR-Spheres Y-90 resin microspheres are the first and only microspheres with FDA premarket approval (PMA) for colorectal cancer that has metastasized to the liver.5 SIR-Spheres® Y-90 resin microspheres are a medical device used in an interventional radiology procedure known as selective internal radiation therapy (SIRT), or radioembolization, which targets high doses of radiation directly to liver tumors. The treatment consists of tens of millions of radioactive Y-90 coated resin particles, each no bigger in diameter than a human hair. Interventional radiologists inject these resin particles, or microspheres, into the hepatic artery via a catheter inserted into the femoral artery through an incision in the groin. The Y-90 resin microspheres become lodged in the capillaries that surround liver tumors, where they deliver a high dose of short-range (mean 2.5 mm; maximum 11 mm) beta radiation to the liver tumors, while sparing healthy liver tissue. The low specific gravity of the Y-90 resin microspheres allows the blood flow to distribute the radioactivity within and around the liver tumors. Available at more than 550 treatment centers in the U.S., more than 67,000 doses of SIR-Spheres Y-90 resin microspheres have been supplied worldwide. SIR-Spheres Y-90 resin microspheres have a Premarket Approval (PMA) by the FDA and are indicated for the treatment of non-resectable metastatic liver tumors from primary colorectal cancer in combination with intra-hepatic artery chemotherapy using floxuridine. SIR-Spheres Y-90 resin microspheres are approved for the treatment of inoperable liver tumors in Australia, the European Union, Argentina, Brazil, Canada and several countries in Asia, such as India and Singapore. The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 of the world’s leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. Sirtex Medical Limited (ASX:SRX) is an Australian-based global healthcare business working to improve outcomes in people with cancer. Our current lead product is a targeted radiation therapy for liver cancer called SIR-Spheres Y-90 resin microspheres. More than 67,000 doses have been supplied to treat patients with liver cancer at more than 1,000 medical centers in over 40 countries. SIR-Spheres® is a registered trademark of Sirtex SIR-Spheres Pty Ltd. Sarah Cannon Research Institute is the research arm of Hospital Corporation of America’s global cancer institute, Sarah Cannon. Focused on advancing therapies for patients, it is one of the world’s leading clinical research organizations conducting community-based clinical trials throughout the United States and United Kingdom. Sarah Cannon’s network of strategic sites includes more than 275 physicians who engage in research. The organization has led more than 250 first-in-man clinical trials since its inception in 1993, and has been a clinical trial leader in more than two-thirds of approved cancer therapies over the last 10 years. Additionally, Sarah Cannon offers management, regulatory, and other research support services for drug development and industry sponsors as well as strategic investigator sites through its contract research organization (CRO), Sarah Cannon Development Innovations (formerly known as SCRI Development Innovations). For more information, visit sarahcannon.com.
News Article | December 18, 2016
– Six of Seven TRK Fusion Patients Achieve Confirmed RECIST Partial Responses and All Remain in Response – – All TRK Fusion Patients Remain on Study With Median Follow-Up of 15 Cycles – – Company to Host Investor Conference Call and Webcast on Monday, December 19, 2016 at 8:00 a.m. EST – STAMFORD, Conn., Dec. 18, 2016 (GLOBE NEWSWIRE) -- Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, today announced updated results from its adult Phase 1 open-label, dose-escalation trial of larotrectinib (LOXO-101), a selective inhibitor of tropomyosin receptor kinase (TRK). The data were presented today at the 2016 European Society for Medical Oncology (ESMO) Asia Congress in Singapore. Data from this ongoing Phase 1 trial were last reported at the American Association for Cancer Research (AACR) Annual Meeting in April 2016. As of a November 10, 2016 data cutoff, 59 patients with refractory solid tumors had been enrolled and treated with single agent larotrectinib, including eight patients with cancers harboring TRK fusions. Seven patients with TRK fusion cancers were on study sufficiently long for an efficacy assessment, while an eighth TRK fusion patient had been recently enrolled and was not yet evaluated for response. Six of the seven efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. The seventh patient, as previously reported, demonstrated clear radiographic tumor regressions, including in the central nervous system, and remains on study, but had not met the threshold required for a RECIST response. All responders remained in response, with one patient in cycle 22, one patient in cycle 19, one patient in cycle 18, two patients in cycle 15 and one patient in cycle 11. Each cycle is 28 days, or approximately one month. Larotrectinib has been well tolerated at doses that include and exceed the recommended Phase 2 dose of 100 mg BID. A maximum tolerated dose (MTD) has not been defined. The majority of adverse events reported by the investigators have been mild to moderate. “The depth of responses and durability data with larotrectinib in patients with TRK fusion cancers are among the most promising that we see in oncology Phase 1 clinical trials,” said Todd Bauer, M.D., associate director, drug development and principal investigator, Sarah Cannon Research Institute and presenter of the larotrectinib oral presentation. “We believe our patients would benefit from the addition of larotrectinib to the armamentarium of matched targeted therapies for our patients, as our continued utilization of molecular testing in clinical practice will naturally lead to the identification of patients with TRK fusions.” “We continue to be very pleased with the efficacy and safety data we are seeing across the larotrectinib program,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “We look forward to further evaluating larotrectinib in adults with TRK fusion cancers in our Phase 2 NAVIGATE study and in pediatric patients in the SCOUT Phase 1/2 study, and sharing those data publicly over time.” Larotrectinib (LOXO-101) Phase 1 Results Larotrectinib is currently being evaluated in an ongoing dose-escalation Phase 1 trial in patients with solid tumors refractory to standard therapy. As of November 10, 2016, 59 patients with advanced cancer had been treated at six dose levels: 50 mg QD, 100 mg QD, 100 mg BID, 150 mg BID, 200 mg QD and 200 mg BID. The median age of these patients is 59 (ranging from 19-82) and the median number of prior treatments is three (ranging from 0-24). Safety Analysis Larotrectinib has been well tolerated in the 59 patients treated, including 34 patients at a dose of 100mg BID. Adverse events reported regardless of attribution to study drug are generally consistent with those previously presented. The most common adverse events, largely Grade 1 and 2, include fatigue (37 percent), dizziness (29 percent), anemia (25 percent) and dyspnea (25 percent). No individual Grade 3 or 4 adverse events occurred in more than three patients treated at 100mg BID or more than five patients in the entire study population. The frequency of toxicities did not correlate with dose level. The MTD has not yet been defined. Efficacy Analysis As of November 10, 2016, eight patients with cancers harboring TRK fusions had been enrolled, representing a broad range of tumor types, namely mammary analogue secretory cancer of the salivary glands (MASC, n=3), gastrointestinal stromal tumor (n=2), soft tissue sarcoma, thyroid carcinoma and non-small cell lung cancer. Seven patients with TRK fusion cancers were on study sufficiently long for an efficacy assessment, while an eighth TRK fusion patient had been recently enrolled and was not yet evaluated for response. Six of the seven efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. A seventh patient, as previously reported, demonstrated clear radiographic tumor regressions, including in the central nervous system, and remains on study, but had not met the threshold required for a RECIST response. All responders remained in response, with one patient in cycle 22, one patient in cycle 19, one patient in cycle 18, two patients in cycle 15 and one patient in cycle 11. Each cycle is 28 days, or approximately one month. On Monday, December 19, 2016, Loxo Oncology plans to file a Form 8-K with the U.S. Securities and Exchange Commission (SEC) containing the larotrectinib materials presented at the ESMO Asia meeting. These materials will also be posted to the Loxo Oncology website. Conference Call and Webcast Information Loxo Oncology will host a conference call and live webcast with slides and Q&A on Monday, December 19, 2016 at 8:00 a.m. ET to discuss the larotrectinib data and provide a comprehensive program and pipeline update. The company will issue a press release prior to the start of the call. The company anticipates that the conference call and webcast will last 60-90 minutes. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 16640119. A live webcast of the presentation will be available at http://ir.loxooncology.com/. A replay of the webcast will be available shortly after the conclusion of the call and archived on the company's website for 30 days following the call. About Larotrectinib (LOXO-101) Larotrectinib (LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, larotrectinib has demonstrated encouraging preliminary efficacy. Larotrectinib is also being evaluated in the NAVIGATE global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions, and the SCOUT Phase 1/2 trial in pediatric patients, including patients with advanced cancer, TRK gene fusions and infantile fibrosarcoma. Larotrectinib has been granted Breakthrough Therapy Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com. About Loxo Oncology Loxo Oncology is a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers. Our pipeline focuses on cancers that are uniquely dependent on single gene abnormalities, such that a single drug has the potential to treat the cancer with dramatic effect. We believe that the most selective, purpose-built medicines have the highest probability of maximally inhibiting the intended target, thereby delivering best-in-class disease control and safety. Our management team seeks out experienced industry partners, world-class scientific advisors and innovative clinical-regulatory approaches to deliver new cancer therapies to patients as quickly and efficiently as possible. For more information, please visit the company's website at www.loxooncology.com. Forward Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, statements we make regarding the timing and success of our clinical trials, the potential therapeutic benefits and economic value of our lead product candidate or other product candidates, and timing of future filings. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q, and other reports as filed from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
News Article | November 15, 2016
SEATTLE, Nov. 15, 2016 (GLOBE NEWSWIRE) -- Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, today announced that two abstracts on the Company’s lead product candidate tucatinib (also known as ONT-380) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) to be held December 6-10 in San Antonio, TX. The Phase 1b “Triplet” poster presentation will include more mature progression-free survival (PFS) and safety data not included in the abstract posted on the SABCS website, which was as of May 2016. A Phase 2 Randomized, Double-Blinded, Controlled Study of ONT-380 vs. Placebo in Combination with Capecitabine (C) and Trastuzumab (T) in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma (MBC) (HER2CLIMB) First Author: Erika Hamilton, Sarah Cannon Research Institute, Nashville, TN Poster/Session: OT1-02-09, Ongoing Trials – Chemotherapy Date/Time: Wednesday, December 7, 2016; 5:00 p.m.–7:00 p.m. CST Efficacy Results of a Phase 1b Study of ONT-380, an Oral HER2-Specific Inhibitor, in Combination with Capecitabine (C) and Trastuzumab (T) in HER2+ Metastatic Breast Cancer (MBC), Including Patients (pts) with Brain Metastases (mets) First Author: Erika Hamilton, Sarah Cannon Research Institute, Nashville, TN Poster/Session: P4-21-01, Treatment: HER2-Targeted Therapy Date/Time: Friday, December 9, 2016; 7:30 a.m.–9:00 a.m. CST Cascadian Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative product candidates for the treatment of cancer. The lead product candidate, tucatinib, also known as ONT-380, is an oral, selective small molecule HER2 inhibitor. Preliminary results from two ongoing Phase 1b studies of tucatinib in combination showed promising systemic activity, a favorable safety profile and encouraging activity against brain metastases. Cascadian Therapeutics is conducting a randomized, double-blind, placebo-controlled Phase 2 study called HER2CLIMB. The study is evaluating tucatinib versus placebo in combination with capecitabine and trastuzumab in late stage HER2+ breast cancer patients, with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and T-DM1. Additional details can be found at www.clinicaltrials.gov (Identifier: NCT02614794) or www.HER2CLIMB.com. For more information and to sign up for email alerts or RSS feeds, please visit www.cascadianrx.com.
News Article | December 6, 2016
BOSTON--(BUSINESS WIRE)--Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, today announced the presentation of results from the DYNAMO® study, a Phase 2 clinical trial evaluating the safety and efficacy of duvelisib in patients with indolent non-Hodgkin lymphoma (iNHL) that is double refractory to both rituximab and chemotherapy, at the American Society of Hematology (ASH) 2016 Annual Meeting held December 3-6, 2016 in San Diego. Duvelisib is an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma that has demonstrated clinical activity as a monotherapy in multiple hematologic cancers, including chronic lymphocytic leukemia (CLL), iNHL and T cell lymphomas. Results from the study were presented by Dr. Ian Flinn in an oral presentation, “DYNAMO: A phase 2 study demonstrating the clinical activity of duvelisib in patients with refractory indolent non-Hodgkin lymphoma.” (Abstract number: 1218) Ian Flinn, M.D., Ph.D., Director of the Blood Cancer Research Program at Sarah Cannon Research Institute and the principal investigator on the DYNAMO study, described the results demonstrating duvelisib’s clinical activity in patients with double refractory iNHL, which included robust and durable responses, and a manageable safety profile. The DYNAMO study included 129 evaluable patients with double refractory iNHL (median 3 prior anticancer regimens, range 1-18). The overall response rate (ORR) was 46% as determined by independent review committee (IRC; p=0.0001; 95% CI 0.37-0.55). Among disease subgroups, the ORR was 41% in follicular lymphoma (n=83), 68% in small lymphocytic lymphoma (n=28), and 33% in marginal zone lymphoma (n=18). Median duration of response (DOR) among all patients was 9.9 months. Notably, 83% of patients had reductions in the size of their target lymph nodes per IRC. Duvelisib was generally well tolerated, with an expected and manageable safety profile with appropriate risk mitigation. The most common Grade ≥3 adverse events (occurring in ≥10% of patients) included neutropenia (28%), infection (18%), diarrhea (15%), thrombocytopenia (13%) and anemia (12%). Dr. Flinn commented, “These results from the DYNAMO study presented at ASH this year clearly show that duvelisib is clinically active with benefit observed across a variety of disease subtypes. It is important to recognize how heavily pre-treated the DYNAMO patients were, being refractory to both rituximab and chemotherapy. This patient population needs more treatment options.” “We are very encouraged by these results,” said Gregory I. Berk, M.D., Chief Medical Officer of Verastem. “The activity and safety of duvelisib observed in the DYNAMO trial are just more evidence of the potential of this drug. We are committed to continuing duvelisib’s development with the belief that it may represent a valuable treatment for patients with very few treatment options.” A copy of the DYNAMO oral presentation is available here. The following is a summary of other presentations at ASH 2016: Title: Preliminary results in first-line treatment of follicular lymphoma with the oral dual PI3K-delta,gamma inhibitor, duvelisib, in combination with rituximab or obinutuzumab Lead Author: Carla Casulo, M.D., Assistant Professor, Wilmot Cancer Institute, University of Rochester Abstract Number: 2979 Date and Time: Sunday, December 4, 2016, 6:00 - 8:00 pm PT The poster can be viewed here. Title: Inhibition of FAK Exerts Anti-Leukemic Activity and Potentiates ABT-199-Induced Apoptosis in AML Lead Author: Bing Carter, Ph.D., Associate Professor, Department of Leukemia - Research, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center Abstract Number: 1574 Date and Time: Saturday, December 3, 2016, 5:30 – 7:30 pm PT The poster can be viewed here. More About the Phase 2 DYNAMO® Study The DYNAMO® study is a Phase 2, single-arm study which evaluated the efficacy and safety of duvelisib (25 mg twice daily) as a monotherapy in 129 patients with follicular lymphoma (n=83), small lymphocytic lymphoma (n=28) or marginal zone lymphoma (n=18) whose disease has progressed and who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was overall response rate as assessed by an independent review committee. The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib and defactinib target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy. Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signaling may lead to the proliferation of malignant B cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO®, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)4, and DYNAMO®, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data5. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov. Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signaling in response to cellular adhesion and growth factors.7 Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumor microenvironment, enhancement of anti-tumor immunity, and reduction of cancer stem cells.8,9 Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab and avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.10,11,12 Information about these and additional clinical trials evaluating the safety and efficacy of defactinib can be found on www.clinicaltrials.gov. Verastem, Inc. (NASDAQ:VSTM) is a biopharmaceutical company focused on discovering and developing drugs to improve outcomes for patients with cancer. Verastem is currently developing duvelisib, a dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, which has successfully met its primary endpoint in a Phase 2 study and is currently being evaluated in a Phase 3 clinical trial in patients with chronic lymphocytic leukemia (CLL). Other clinical product candidates include focal adhesion kinase (FAK) inhibitors defactinib (VS-6063) and VS-4718, and dual PI3K/mTOR inhibitor VS-5584. Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types, including pancreatic, ovarian and non-small cell lung cancer, and mesothelioma. Verastem’s product candidates seek to treat cancer by modulating the local tumor microenvironment, enhancing anti-tumor immunity and reducing cancer stem cells. For more information, please visit www.verastem.com. This press release includes forward-looking statements about Verastem’s strategy, future plans and prospects, including statements regarding results of the Phase 2 DYNAMO® study, and Verastem’s PI3K/mTOR and FAK programs generally, the structure of our planned and pending clinical trials and the timeline and indications for clinical development, including reporting top-line data, and regulatory submissions and, our rights to develop or commercialize our product candidates. The words “anticipate,” “appear,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks that the preclinical testing of Verastem’s product candidates and preliminary or interim data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that data may not be available when expected, including for the Phase 3 DUO study; that enrollment of clinical trials may take longer than expected; that our product candidates will cause unexpected safety events or result in an unmanageable safety profile as compared to their level of efficacy; that duvelisib will be ineffective at treating patients with lymphoid malignancies; that Verastem will be unable to successfully initiate or complete the clinical development of its product candidates; that the development of Verastem’s product candidates will take longer or cost more than planned; that Verastem may not have sufficient cash to fund its contemplated operations; that Verastem or Infinity will fail to fully perform under the license agreement; that the transition of the duvelisib program from Infinity will not be completed; that Verastem will not pursue or submit regulatory filings for its product candidates, including for duvelisib in patients with CLL or iNHL; and that Verastem’s product candidates will not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients. Other risks and uncertainties include those identified under the heading “Risk Factors” in Verastem’s Annual Report on Form 10-K for the year ended December 31, 2015 as filed on March 3, 2016, the Company’s quarterly report on Form 10-Q filed on November 7, 2016, and in any subsequent SEC filings. The forward-looking statements contained in this press release reflect Verastem’s current views with respect to future events, and Verastem does not undertake and specifically disclaims any obligation to update any forward-looking statements. 1 Winkler D.G., Faia K.L., DiNitto J.P. et al. PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol 2013; 20:1-11. 2 Reif K et al.Cutting Edge: Differential Roles for Phosphoinositide 3 kinases, p110-gamma and p110-delta, in lymphocyte chemotaxis and homing. J Immunol 2004:173:2236-2240. 3 Schmid M et al. Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly activate myeloid cell PI3K, a single convergent point promoting tumor inflammation and progression. Cancer Cell 2011;19:715-727. 4 www.clinicaltrials.gov, NCT02004522 5 www.clinicaltrials.gov, NCT01882803 6 www.clinicaltrials.gov, NCT02783625, NCT02783625, NCT02158091 7Schaller M.D. and Parsons JT. Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 3: 258-62. 8Jiang H et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 2016: Aug 22(8) 851-60. 9Sulzmaier FJ et al. FAK in cancer: mechanistic findings and clinical applications. Nature Rev Cancer. 2014 14: 598-610. 10www.clinicaltrials.gov, NCT02546531 11www.clinicaltrials.gov, NCT02943317 12www.clinicaltrials.gov, NCT02758587
Combined modality treatment with chemotherapy, radiation therapy, bevacizumab, and erlotinib in patients with locally advanced squamous carcinoma of the head and neck: A phase II trial of the sarah cannon oncology research consortium
Hainsworth J.D.,Sarah Cannon Research Institute PLLC |
Hainsworth J.D.,Tennessee Oncology PLLC |
Spigel D.R.,Sarah Cannon Research Institute PLLC |
Spigel D.R.,Tennessee Oncology PLLC |
And 10 more authors.
Cancer Journal | Year: 2011
PURPOSE: The aim of the study was to evaluate the feasibility and efficacy of adding bevacizumab and erlotinib to concurrent chemoradiation therapy for first-line treatment of patients with locally advanced squamous carcinoma of the head and neck. METHODS: Sixty previously untreated patients with squamous carcinoma of the head and neck (36 with oropharyngeal primaries; 83% men; median age, 56 years; 73% stage IV) received induction chemotherapy with 6 weeks of paclitaxel, carboplatin, infusional 5-fluorouracil, and bevacizumab; this treatment was followed by radiation therapy, weekly paclitaxel, bevacizumab, and erlotinib. RESULTS: After a median follow up of 32 months, the estimated 3-year progression-free and overall survival rates are 71% and 82%, respectively. Sixty-five percent of patients had major responses after induction therapy; after completion of therapy, 95% of patients had either partial or complete response radiographically. As expected, grade 3/4 mucosal toxicity occurred frequently (88%) during combined modality; no unexpected toxicity resulted from the addition of bevacizumab and erlotinib. CONCLUSIONS: The addition of bevacizumab and erlotinib to first-line combined modality therapy was feasible in a community-based setting, producing toxicity comparable to other effective combined modality regimens for head and neck cancer. The high level of efficacy suggests that incorporation of these targeted agents into first-line therapy should be further explored.