Takeda Announces Phase 3 Trial of ALUNBRIG® (brigatinib) Met Primary Endpoint Demonstrating Superiority in Progression-Free Survival Versus Crizotinib in Patients with ALK+ Advanced NSCLC Who are ALK Inhibitor Naïve
Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the global, randomized, Phase 3 ALTA-1L (ALK in Lung Cancer Trial of AP26113 in 1 st Line) trial met its primary endpoint at the first pre-specified interim analysis, with ALUNBRIG® (brigatinib) demonstrating a statistically significant improvement in progression-free survival (PFS) compared to crizotinib in adults with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor. The trial was designed to assess the efficacy and safety of ALUNBRIG in comparison to crizotinib based on evaluation of the primary endpoint of PFS, or length of time from the start of treatment that a patient lives without the disease getting worse. ALUNBRIG is currently not approved as frontline therapy.
“This represents a major milestone for the ALUNBRIG program. Our goal with ALUNBRIG is to improve the lives of patients with ALK+ NSCLC by furthering the available therapeutic options,” said Jesús Gomez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “We are encouraged by the data, which demonstrated a statistically significant improvement in progression-free survival versus crizotinib in patients with ALK+ advanced NSCLC, and look forward to beginning discussions with regulatory authorities as we seek to expand ALUNBRIG’s indication into the frontline setting.”
The safety profile associated with ALUNBRIG from the ALTA-1L trial was generally consistent with the existing prescribing information, with no new safety concerns.
The results from this interim analysis will be submitted for presentation at an upcoming medical meeting.
About the ALTA-1L Trial
The Phase 3 ALTA-1L (ALK in Lung Cancer Trial of AP26113 in 1 st Line) trial of ALUNBRIG in adults is a global, ongoing, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Patients received either ALUNBRIG, 180 mg once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg twice daily. Independent Review Committee (IRC)-assessed progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR) per RECIST v1.1, intracranial ORR, intracranial PFS, overall survival (OS), safety and tolerability. A total of approximately 198 PFS events are planned at the final analysis of the primary endpoint in order to demonstrate a minimum of six months PFS improvement over crizotinib. The trial is designed with two pre-specified interim analyses for the primary endpoint – one at 50 percent of planned PFS events and one at 75 percent of planned PFS events.
About ALK+ NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.
Takeda is committed to continuing research and development in NSCLC to improve the lives of the approximately 40,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year.
About ALUNBRIG ® (brigatinib)
ALUNBRIG is a targeted cancer medicine discovered by ARIAD Pharmaceuticals, Inc., which was acquired by Takeda in February 2017. In April 2017, ALUNBRIG received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for ALK+ metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
ALUNBRIG received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib and was granted Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC. A Marketing Authorization Application (MAA) for ALUNBRIG was submitted to the European Medicines Agency (EMA) in February 2017.
The brigatinib clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with ALK+ NSCLC worldwide and the healthcare professionals who treat them. The comprehensive program includes the following clinical trials:
- Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG
- Pivotal Phase 2 ALTA trial investigating the efficacy and safety of ALUNBRIG at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib
- Phase 3 ALTA-1L trial assessing the efficacy and safety of ALUNBRIG in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor
- Phase 2 single-arm, multicenter study in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
- Phase 2 global study evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
IMPORTANT SAFETY INFORMATION (U.S.)
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with ALUNBRIG. In Trial ALTA (ALTA), ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). Adverse reactions consistent with possible ILD/pneumonitis occurred early (within 9 days of initiation of ALUNBRIG; median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%. Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating ALUNBRIG. Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG with dose reduction after recovery to baseline or permanently discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.
Hypertension: In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received ALUNBRIG and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1 severity, resume ALUNBRIG at a reduced dose. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension. Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia.
Bradycardia: Bradycardia can occur with ALUNBRIG. In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided. For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ALUNBRIG at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution of symptomatic bradycardia. Discontinue ALUNBRIG for life-threatening bradycardia if no contributing concomitant medication is identified.
Visual Disturbance: In ALTA, adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group. Advise patients to report any visual symptoms. Withhold ALUNBRIG and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume ALUNBRIG at a reduced dose. Permanently discontinue treatment with ALUNBRIG for Grade 4 visual disturbances.
Creatine Phosphokinase (CPK) Elevation: In ALTA, creatine phosphokinase (CPK) elevation occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and 48% of patients in the 90 mg→180 mg group. The incidence of Grade 3-4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group. Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% in the 90→180 mg group. Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4 CPK elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.
Pancreatic Enzyme Elevation: In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.
Hyperglycemia: In ALTA, 43% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving ALUNBRIG. Assess fasting serum glucose prior to initiation of ALUNBRIG and monitor periodically thereafter. Initiate or optimize anti-hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and consider reducing the dose of ALUNBRIG or permanently discontinuing ALUNBRIG.
Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to pregnant women. There are no clinical data on the use of ALUNBRIG in pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG.
Serious adverse reactions occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. The most common serious adverse reactions were pneumonia (5.5% overall, 3.7% in the 90 mg group, and 7.3% in the 90→180 mg group) and ILD/pneumonitis (4.6% overall, 1.8% in the 90 mg group and 7.3% in the 90→180 mg group). Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each).
The most common adverse reactions (≥25%) in the 90 mg group were nausea (33%), fatigue (29%), headache (28%), and dyspnea (27%) and in the 90→180 mg group were nausea (40%), diarrhea (38%), fatigue (36%), cough (34%), and headache (27%).
CYP3A Inhibitors: Avoid concomitant use of ALUNBRIG with strong CYP3A inhibitors. Avoid grapefruit or grapefruit juice as it may also increase plasma concentrations of brigatinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG.
CYP3A Inducers: Avoid concomitant use of ALUNBRIG with strong CYP3A inducers.
CYP3A Substrates: Coadministration of ALUNBRIG with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of CYP3A substrates.
USE IN SPECIFIC POPULATIONS
Pregnancy: ALUNBRIG can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.
Lactation: There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with ALUNBRIG.
Females and Males of Reproductive Potential:
Contraception: Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose.
Infertility: ALUNBRIG may cause reduced fertility in males.
Pediatric Use: The safety and efficacy of ALUNBRIG in pediatric patients have not been established.
Geriatric Use: Clinical studies of ALUNBRIG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Of the 222 patients in ALTA, 19.4% were 65-74 years and 4.1% were 75 years or older. No clinically relevant differences in safety or efficacy were observed between patients ≥65 and younger patients.
Hepatic or Renal Impairment: No dose adjustment is recommended for patients with mild hepatic impairment or mild or moderate renal impairment. The safety of ALUNBRIG in patients with moderate or severe hepatic impairment or severe renal impairment has not been studied.
Please see the full U.S. Prescribing Information for ALUNBRIG at www.ALUNBRIG.com
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Approximately 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries. For more information, visit https://www.takeda.com/newsroom/.
Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.
Takeda Pharmaceutical Company Limited
Kazumi Kobayashi, +81 3 3 278 2095
Kate Burd, +41 79 514 9533
Media outside Japan/EU
Shant Salakian, +1-617-444-3334
Om Business Wire
(c) 2018 Business Wire, Inc., All rights reserved.
Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.
Følg saker fra Business Wire
Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.
Siste saker fra Business Wire
Mouser Electronics and Grant Imahara Launch New Series All Things IoT about Technology Redefining How We Live17.10.2018 15:40 | Pressemelding
Mouser Electronics Inc. and celebrity engineer Grant Imahara today released a new video introducing All Things IoT, the latest series in Mouser’s award-winning Empowering Innovation Together™ program. The All Things IoT series is sponsored by Mouser’s valued suppliers Digi International, Maxim Integrated, Murata and TE Connectivity. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181017005655/en/ Global distributor Mouser Electronics and engineer spokesperson Grant Imahara team up to launch All Things IoT, the latest series in Mouser's Empowering Innovation Together program. The new series kicks off with Imahara's visit to the HPE IoT Innovation Lab in Houston to learn how the Internet of Things is impacting our workplaces and cities. To learn more, visit www.mouser.com/empowering-innovation/all-things-iot. (Photo: Business Wire) In the new video, Imahara and Mouser explore the complexities of life rooted in the Internet of T
Telefónica Deutschland Selects Mavenir vIMS for Deployment on ‘UNICA’17.10.2018 14:59 | Pressemelding
Mavenir, the leader in accelerating and redefining mobile network economics transformation for Communications Service Providers (CSPs), today announced that Telefónica Deutschland (FWB: O2D) is deploying Mavenir’s virtualized IMS solution (vIMS) for VoLTE and VoWiFi in their nationwide UNICA Data Centers Infrastructure, which is based on the Telefónica Group blueprint for Network Functions Virtualization (NFV) architecture. The solution will support mobile and fixed services for more than 45 million customer connections. The NFV environment is based on OpenStack® and will include automation, life cycle management and integration with Management and Orchestration (MANO) capabilities from the Telefónica UNICA platform. The Mavenir advanced vIMS solution will enable automation from day one and will support existing voice digital services as well as the launch of new services. As a software-based company leading the Telco NFV industry, Mavenir is a perfect match with Telefónica UNICA NFV s
Lenovo and Scale Computing Collaborate to Solve Edge Infrastructure Challenges for Retailers17.10.2018 14:34 | Pressemelding
Lenovo (HKSE: 992) (ADR: LNVGY), a Global Fortune 500 company and a technology leader in Intelligent Transformation, and Scale Computing, a market leader in intelligent edge solutions, today announced a global partnership and a new joint product providing a solution for edge infrastructure for global retailers, distributed enterprises and small and medium-sized businesses. The solution is ideal for highly distributed, on-premise environments, such as retail stores or bank branches, with multiple locations managed by the enterprise from a central location. Lenovo’s broad range of servers combined with efficient, intelligent edge infrastructure software from Scale Computing deliver a simple, self-healing, highly-available platform for running applications at the edge or hybrid edge-and-cloud. The Scale Computing HC3 Edge Platform on Lenovo Servers replaces traditional complex and expensive on-premise infrastructure with a modern solution optimized for environments where application uptim
As Hilton Nears 100-Year Milestone, New Research Uncovers a World-Changing Impact17.10.2018 13:24 | Pressemelding
As Hilton (NYSE: HLT) heads toward a milestone 100th anniversary in 2019, best-selling author and Stanford Business professor Chip Heath will unveil the impact the first global hotel company has had around the world in a new book titled The Hilton Effect. Business author Karla Starr joined him in the examination of the company founded by Conrad Hilton, a dreamer who aspired to create much more than just a comfortable place to sleep. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181017005486/en/ As Hilton nears 100-year milestone, new research uncovers a world-changing impact. (Graphic: Business Wire) Over the last century, Hilton has grown from a single hotel in Cisco, Texas, to nearly 5,500 hotels and 14 brands in 106 countries and territories. Hilton’s hotels have hosted more than 3 billion guests since 1919 and enlisted nearly 10 million Team Members in the company’s mission to fill the Earth with the light and warmth of
Infovista Announces Channel Go-to-Market Strategy for 5G, Application-Aware SD-WAN Solutions17.10.2018 13:00 | Pressemelding
Reinforcing its commitment to the channel to deliver its industry-leading 5G, application-aware SD-WAN and network testing solutions to market, Infovista, the leader in modern network performance, today announced its go-to-market strategy is “all indirect, all the time.” To accelerate its global channel strategy, Infovista has hired industry veteran Jon Howes as senior vice president, global channel sales. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181017005042/en/ Jon Howes, Senior Vice President Global Channel Sales (Photo: Business Wire) Howes is responsible for leading Infovista’s indirect go-to-market strategy for all products. Howes, an accomplished channel leader with a long history of managing high-performance channel and business development teams, has expertise spanning multiple geographies in both service provider and enterprise end user environments. Prior to joining Infovista, Howes built channels for Junipe
Smart Link Accelerates Digital Service Expansion with Avaya Cloud Contact Center Solutions17.10.2018 12:37 | Pressemelding
Smart Link, a subsidiary of Al Khaleej for Training and Education and a leading Saudi-based Business Process Outsourcing (BPO) company, has teamed up with Avaya Holdings Corp. (NYSE:AVYA) to accelerate Smart Link’s expansion and the diversification of its digital services portfolio. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181017005478/en/ Avaya signs a Memorandum of Understanding with Smart Link during GITEX Technology Week 2018 (Photo: Business Wire) The two companies signed a Memorandum of Understanding (MoU) during GITEX Technology Week with a focus on digital and cloud-based solutions that will enable Smart Link to have greater agility and flexibility in meeting its customers’ demands for digital services. In alignment with Saudi Vision 2030, Smart Link is digitalizing and automating all possible duties to increase its human value while delivering cutting-edge communication solutions to connect government and priv