Takeda to Feature ALUNBRIG™ (brigatinib) Data from Pivotal Phase 2 ALTA Trial at 18th World Conference on Lung Cancer
Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the company will present four company-sponsored abstracts, including one oral presentation, at the 18th World Conference on Lung Cancer (WCLC) of the International Association for the Study of Lung Cancer (IASLC), October 15-18, in Yokohama, Japan. Presentations at this year’s meeting will highlight Takeda’s progress in developing ALUNBRIGTM (brigatinib), an anaplastic lymphoma kinase (ALK) inhibitor in non-small cell lung cancer (NSCLC). As part of a deep commitment to advancing research and serving the needs of patients, Takeda aspires to develop best-in-class treatments for people living with NSCLC.
“The presentations at this year’s meeting support the role of ALUNBRIG as a targeted therapy for patients with advanced ALK-positive NSCLC,” said Jesus Gomez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “Updated data being presented at WCLC from the pivotal ALTA trial reinforces, with longer follow-up, the clinical findings previously reported. We are committed to continuing research and development in NSCLC to improve the lives of the more than 30,000 patients diagnosed with ALK+ NSCLC worldwide each year.”
During the oral presentation, Takeda will feature updated data from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial, highlighting the efficacy and safety of ALUNBRIG at two separate dosing regimens in patients with advanced ALK+ NSCLC who have progressed on crizotinib. Additional efficacy and safety sub-analyses from the trial will also be presented.
The four Takeda-sponsored abstracts accepted for presentation during
WCLC 2017 include:
Note: all times listed are in Japan Standard Time.
- Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Updated Efficacy and Safety Results From ALTA, a Randomized Phase 2 Trial. Abstract 8027. Oral presentation. Monday, October 16, 4:30 – 4:40 p.m., Room 301 & 302.
- Hypertension With Brigatinib: Experience in ALTA, a Randomized Phase 2 Trial in Crizotinib-Refractory ALK+ NSCLC. Abstract 8346. Monday, October 16, 9:30 a.m.- 4:00 p.m., Exhibit Hall (Hall B + C).
- Depth of Target Lesion Response to Brigatinib and Its Association With Outcomes in Patients With ALK+ NSCLC in the ALTA Trial. Abstract 8035. Monday, October 16, 9:30 a.m.- 4:00 p.m., Exhibit Hall (Hall B + C).
- Overall Survival (OS) After Disease Progression on Brigatinib in Patients With Crizotinib-Refractory ALK+ NSCLC in ALTA. Abstract 8546. Monday, October 16, 9:30 a.m.- 4:00 p.m., Exhibit Hall (Hall B + C).
About the ALTA Trial
The Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of brigatinib in adults is an ongoing, two-arm, open-label, multicenter trial, which enrolled 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib. Patients received either 90 mg of ALUNBRIG once daily (n=112) or 180 mg once daily following a seven-day lead-in of 90 mg once daily (n=110). The major efficacy outcome measure was confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by an Independent Review Committee (IRC). Additional efficacy outcome measures included Investigator-assessed ORR, duration of response (DOR), intracranial ORR, and intracranial DOR.
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 222,500 new cases of lung cancer diagnosed each year in the United States, according to the American Cancer Society. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately two to eight percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.
The central nervous system (CNS) is a frequent site for progression in ALK+ NSCLC, with brain metastases present in up to 70 percent of patients after treatment with crizotinib.
About ALUNBRIG ® (brigatinib)
ALUNBRIG is a targeted cancer medicine discovered by ARIAD Pharmaceuticals, Inc., which was acquired by Takeda in February 2017. ALUNBRIG recently received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for ALK+ 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.
In the US, the recommended dosing regimen for ALUNBRIG is:
- 90 mg orally once daily for the first 7 days;
- if 90 mg is tolerated during the first 7 days, increase the dose to 180 mg orally once daily.
The ALTA 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. In addition to the ongoing Phase 1/2 and Phase 2 ALTA trial, brigatinib is also being studied in the Phase 3 ALTA 1L trial to assess its efficacy and safety in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor.
IMPORTANT SAFETY INFORMATION
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 Prescribing Information for ALUNBRIG at www.ALUNBRIG.com
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited 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 central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.
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
Tsuyoshi Tada, +81 (0) 3-3278-2417
Kate Burd, +44 7974 151510
Media outside Japan/EU
Amy Atwood, +1-617-551-3683
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Tilaa tiedotteet sähköpostiisi
Haluatko tietää asioista jo ennen kuin ne uutisoidaan? Kun tilaat tiedotteemme, saat ne sähköpostiisi yhtä aikaa suomalaisen median kanssa. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
Inside Secure to Provide Secure Provisioning Solutions to NationalChip18.6.2018 18:35 | Tiedote
Regulatory News: Inside Secure (Paris:INSD), at the heart of security solutions for mobile and connected devices, announced it entered into an agreement with Hangzhou NationalChip Science and Technology Co., Ltd, a leading innovator and developer of SoCs (system-on-chip), to use Inside Secure’s Secure Provisioning Solution to build robust security into its products during the chip manufacturing process. Secure provisioning is recognized as a crucial, foundational security building block across diverse markets including automotive, entertainment, IoT, mobile and TV. Securing devices or end products can be worthless if their identities and cryptographic keys have been compromised during manufacturing. Widely-publicized attacks have targeted provisioning because they can affect large numbers of devices and are difficult to detect. Chipmakers and device manufacturers see the potential for new revenue sources by offering secure provisioning to their customers, leveraging technology solution
Citi Private Bank Congratulates Fernando Alonso on the 24 Hours of Le Mans Win18.6.2018 17:01 | Tiedote
Citi Private Bank ardently congratulates Fernando Alonso for his impressive win at The 24 Hours of Le Mans this past weekend. Mr. Alonso, who is also a two time Formula One World Champion, most recently competed and won the Six Hours of Spa-Francorchamps in May. In January he debuted at the Rolex 24 at Daytona. Previously he participated in the Indianapolis 500 in May of 2017. He was sponsored by Citi Private Bank for all four races. Alongside the Indianapolis 500 and the Monaco Grand Prix, Le Mans makes up one third of ‘the Triple Crown of Motor Racing’. Having already won Monaco twice, Mr. Alonso is on a quest to become only the second driver in history to complete the Triple Crown. “Fernando drove one the most thrilling races at Le Mans that I have ever seen. His stunning night time drive will likely go down as one of the greatest victories in motorsport’s history,” said Peter Clive Charrington, Global Head of Citi Private Bank. “Fernando possesses an unrelenting drive toward excell
Inteva Products Receives Top Innovation Award for Revolutionary Stitching Process18.6.2018 16:31 | Tiedote
Inteva Products, LLC, a leading global Tier One automotive supplier of engineered components and systems, received the top prize in the 2018 Innovation Awards presented by the European Association of Automotive Suppliers (CLEPA) at The Hague, Netherlands, on June 13. Inteva was recognized for its new real-time scanning process for the robotic stitching of automotive interiors. This innovative technology will be used on instrument panels for the 2019 Chevrolet Silverado and GMC Sierra pickup trucks. The new process enables “live” scanning and immediate adjustments to the program path of robotic stitching equipment as a component is being stitched. This approach aligns leading-edge advances in the use of lasers in automotive manufacturing with Inteva’s unique robotic stitching technologies. The advancement reduces the average cycle time of a stitched surface by approximately 20-30%. The 2018 CLEPA Innovation Awards, organized in cooperation with Deloitte, celebrate automotive excellence
P&G Advances Systemic Change for Gender Equality in Advertising at 2018 Cannes Lions Festival of Creativity18.6.2018 15:25 | Tiedote
The Procter & Gamble Company (NYSE: PG) today advanced its commitment to gender equality through a series of new actions, commitments and partnerships to increase diversity throughout the creative supply chain, leading to more accurate and positive portrayals of women in advertising and media, and driving growth and social good. Women and girls are inaccurately or negatively portrayed in 29 percent of ads and media programs*, and women continue to be underrepresented behind the camera: only 32 percent of Chief Marketing Officers, 33 percent of Chief Creative Officers and a mere 10 percent of Commercial Directors are women. These issues persist despite evidence that gender-equal ads perform 10 percent higher in trust and 26 percent higher in sales growth*. To address these issues, P&G has called for an aspiration to achieve 100% accurate and positive portrayals of women in advertising and media, supported by equal representation of women and men in the creative supply chain. P&G is lead
Norsk Titanium Marks Milestone in U.S. Production18.6.2018 15:00 | Tiedote
Norsk Titanium (NTi), the world’s first FAA-approved supplier of aerospace-grade, additive manufactured, structural titanium components, announced today a major milestone in qualified production. NTi’s Plattsburgh, New York Development and Qualification Center (PDQC) site was officially added to Boeing’s Qualified Producers List (QPL) on May 1 and initiated qualified production on May 15 by manufacturing its first part under the Boeing contract. This milestone is a culmination of recent company successes including certification under AS9100D and the October 2017 dedication of PDQC by New York Governor Andrew Cuomo. “We could not be prouder of our Plattsburgh, New York production operations as they put another stake in the ground for the continued success of Norsk Titanium and the state of New York,” said NTi’s Chief Operating Officer Tamara Morytko. “Receiving this qualification from Boeing, now qualifying two NTi sites for production across the globe, is a true vote of confidence in o
Avedro Announces Enrollment of First Patient in U.S. Pivotal Phase 3 Epi-on Corneal Cross-Linking Trial for Progressive Keratoconus18.6.2018 15:00 | Tiedote
Avedro, Inc., an ophthalmic pharmaceutical and medical device company and the world leader in corneal remodeling, today announced that it has begun enrolling patients in a pivotal Phase 3 clinical trial to evaluate the safety and efficacy of an epithelium-on (epi-on) corneal collagen cross-linking procedure to treat patients with progressive keratoconus. Keratoconus is a non-inflammatory eye condition in which the typically round dome-shaped cornea progressively thins and weakens and is the leading cause of penetrating keratoplasty (corneal transplant) in the United States1. The Phase 3 clinical trial, ACP-KXL-308, is a multicenter, randomized, controlled study of a novel corneal cross-linking procedure of 275 patients with progressive keratoconus across approximately 20 sites in the United States. As is typical for U.S. Food and Drug Administration (FDA) drug trials, investigational treatments are provided at no cost to participating patients. “As a practitioner who has treated many p
Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.Tutustu uutishuoneeseemme