– Updated Results Continue to Support the Efficacy and Safety Findings for ALUNBRIG with the 180 mg Dosing Regimen in Patients with Advanced ALK+ NSCLC Who Have Progressed on Crizotinib, Per Independent Review Committee:
- Median Progression-Free Survival (PFS) of 16.7 Months
- Sixty-Seven Percent of Patients with Measurable Brain Metastases at Baseline had an Intracranial Objective Response with a Median Duration of Intracranial Response of 16.6 Months –
– Data Will Be Presented in an Oral Session at the IASLC World Conference on Lung Cancer (WCLC) on Monday, October 16 at 4:30 p.m. JST
CAMBRIDGE, MA, USA and OSAKA, Japan I October 16, 2017 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that data from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) clinical trial evaluating ALUNBRIGTM (brigatinib) in patients with locally advanced or metastatic anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who have progressed on crizotinib will be presented in an oral session at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) on Monday, October 16, 4:30 p.m.- 4:40 p.m. JST. The presentation will share updated safety and efficacy data from the trial as of February 21, 2017, which continue to support previously reported clinical results.
The randomized Phase 2 ALTA trial was designed to investigate the efficacy and safety of ALUNBRIG at two dosing regimens. Patients received either 90 mg of ALUNBRIG once daily (n = 112; 90 mg; Arm A) or 180 mg once daily following a seven-day lead-in of 90 mg once daily (n=110; 180 mg dosing regimen; Arm B).
“The data being presented at WCLC provide further evidence supporting the role of ALUNBRIG in the treatment of patients with advanced ALK-positive NSCLC,” said David Kerstein, M.D., Senior Medical Director and Global Clinical Lead for ALUNBRIG, Oncology Clinical Research, Takeda. “There continues to be an unmet need for the more than 30,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year. We are encouraged by the updated data from the ALTA trial, which support the efficacy and safety of ALUNBRIG in a crizotinib-refractory population, at the dosing regimen that is being taken forward into ongoing and future clinical trials.”
“The updated data from the ALTA trial further support the clinical benefit of ALUNBRIG (brigatinib),” said Myung-Ju Ahn, M.D., Professor, Department of Hematology & Oncology, Samsung Medical Center. “I am especially encouraged by the efficacy seen in patients with brain metastases, cancer that has spread to the brain. The central nervous system is a common site for progression in this disease, with brain metastases occurring in up to 70 percent of patients after treatment with crizotinib. With the 180 mg dosing regimen of brigatinib, two-thirds of patients with measurable brain metastases had an intracranial response, with a median intracranial duration of response of 16.6 months.”
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Updated Efficacy and Safety Results From ALTA, a Randomized Phase 2 Trial (Abstract #8027, Oral Presentation on Monday, October 16, 4:30-4:40 p.m. at the PACIFICO Yokohama Convention Center, Rooms 301 & 302)
Follow-up data as of February 21, 2017, 17 months after the last patient enrolled; last brain scan was February 28, 2017.
Key findings, which will be presented by Dr. Myung-Ju Ahn, Samsung Medical Center, include:
- As of February 21, 2017, at a median follow-up period of 16.8 and 18.6 months in Arms A (90 mg once daily) and B (180 mg once daily following a seven-day lead-in of 90 mg once daily), respectively, 32 percent of patients in Arm A and 41 percent of patients in Arm B continued to receive ALUNBRIG.
- Investigator-assessed confirmed objective response rate (ORR), which was the primary endpoint, was 46 percent in Arm A and 55 percent in Arm B. Per Independent Review Committee (IRC), confirmed ORR was 51 percent in Arm A and 55 percent in Arm B.
- Investigator-assessed median duration of response (DOR) was 12 months in Arm A and 13.8 months in Arm B. IRC-assessed median DOR was 13.8 months in Arm A and 14.8 months in Arm B.
- Investigator-assessed median progression-free survival (PFS) was 9.2 months in Arm A and 15.6 months in Arm B. IRC-assessed median PFS was 9.2 months in Arm A and 16.7 months in Arm B.
- Median overall survival (OS) was not reached in Arm A and 27.6 months in Arm B. The one-year OS probability was 70 percent in Arm A and 80 percent in Arm B.
- Of the patients with measurable brain metastases at baseline (n=26 / n=18, Arm A / Arm B), 50 percent in Arm A and 67 percent in Arm B achieved a confirmed intracranial objective response by IRC assessment; median duration of intracranial response was not reached in Arm A and was 16.6 months in Arm B.
- In patients with any brain metastases at baseline the median intracranial PFS as assessed by the IRC was 12.8 months in Arm A and 18.4 months in Arm B.
- The most common grade ≥3 treatment-related adverse events (AEs) (Arm A / Arm B) included increased blood creatine phosphokinase (3 percent / 11 percent), hypertension (4 percent / 4 percent), increased lipase (4 percent / 4 percent), pneumonitis (2 percent / 4 percent), and rash (1 percent / 4 percent). Dose reduction (9 percent / 30 percent) or discontinuation (4 percent / 11 percent) due to any AEs was reported.
- The efficacy and safety data from the ALTA trial continue to support future trials with the 180 mg dosing regimen.
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). Investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 was the primary endpoint. Secondary endpoints included IRC-assessed ORR, duration of response (DOR), intracranial ORR, intracranial PFS, safety and tolerability.
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. In April of 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.
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.
To learn more about ALUNBRIG, please visit www.ALUNBRIG.com or call 1-844-A1POINT (1-844-217-6468). For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 19
– Updated Results Continue to Support the Efficacy and Safety Findings for ALUNBRIG with the 180 mg Dosing Regimen in Patients with Advanced ALK+ NSCLC Who Have Progressed on Crizotinib, Per Independent Review Committee:
- Median Progression-Free Survival (PFS) of 16.7 Months
- Sixty-Seven Percent of Patients with Measurable Brain Metastases at Baseline had an Intracranial Objective Response with a Median Duration of Intracranial Response of 16.6 Months –
– Data Will Be Presented in an Oral Session at the IASLC World Conference on Lung Cancer (WCLC) on Monday, October 16 at 4:30 p.m. JST
CAMBRIDGE, MA, USA and OSAKA, Japan I October 16, 2017 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that data from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) clinical trial evaluating ALUNBRIGTM (brigatinib) in patients with locally advanced or metastatic anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who have progressed on crizotinib will be presented in an oral session at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) on Monday, October 16, 4:30 p.m.- 4:40 p.m. JST. The presentation will share updated safety and efficacy data from the trial as of February 21, 2017, which continue to support previously reported clinical results.
The randomized Phase 2 ALTA trial was designed to investigate the efficacy and safety of ALUNBRIG at two dosing regimens. Patients received either 90 mg of ALUNBRIG once daily (n = 112; 90 mg; Arm A) or 180 mg once daily following a seven-day lead-in of 90 mg once daily (n=110; 180 mg dosing regimen; Arm B).
“The data being presented at WCLC provide further evidence supporting the role of ALUNBRIG in the treatment of patients with advanced ALK-positive NSCLC,” said David Kerstein, M.D., Senior Medical Director and Global Clinical Lead for ALUNBRIG, Oncology Clinical Research, Takeda. “There continues to be an unmet need for the more than 30,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year. We are encouraged by the updated data from the ALTA trial, which support the efficacy and safety of ALUNBRIG in a crizotinib-refractory population, at the dosing regimen that is being taken forward into ongoing and future clinical trials.”
“The updated data from the ALTA trial further support the clinical benefit of ALUNBRIG (brigatinib),” said Myung-Ju Ahn, M.D., Professor, Department of Hematology & Oncology, Samsung Medical Center. “I am especially encouraged by the efficacy seen in patients with brain metastases, cancer that has spread to the brain. The central nervous system is a common site for progression in this disease, with brain metastases occurring in up to 70 percent of patients after treatment with crizotinib. With the 180 mg dosing regimen of brigatinib, two-thirds of patients with measurable brain metastases had an intracranial response, with a median intracranial duration of response of 16.6 months.”
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Updated Efficacy and Safety Results From ALTA, a Randomized Phase 2 Trial (Abstract #8027, Oral Presentation on Monday, October 16, 4:30-4:40 p.m. at the PACIFICO Yokohama Convention Center, Rooms 301 & 302)
Follow-up data as of February 21, 2017, 17 months after the last patient enrolled; last brain scan was February 28, 2017.
Key findings, which will be presented by Dr. Myung-Ju Ahn, Samsung Medical Center, include:
- As of February 21, 2017, at a median follow-up period of 16.8 and 18.6 months in Arms A (90 mg once daily) and B (180 mg once daily following a seven-day lead-in of 90 mg once daily), respectively, 32 percent of patients in Arm A and 41 percent of patients in Arm B continued to receive ALUNBRIG.
- Investigator-assessed confirmed objective response rate (ORR), which was the primary endpoint, was 46 percent in Arm A and 55 percent in Arm B. Per Independent Review Committee (IRC), confirmed ORR was 51 percent in Arm A and 55 percent in Arm B.
- Investigator-assessed median duration of response (DOR) was 12 months in Arm A and 13.8 months in Arm B. IRC-assessed median DOR was 13.8 months in Arm A and 14.8 months in Arm B.
- Investigator-assessed median progression-free survival (PFS) was 9.2 months in Arm A and 15.6 months in Arm B. IRC-assessed median PFS was 9.2 months in Arm A and 16.7 months in Arm B.
- Median overall survival (OS) was not reached in Arm A and 27.6 months in Arm B. The one-year OS probability was 70 percent in Arm A and 80 percent in Arm B.
- Of the patients with measurable brain metastases at baseline (n=26 / n=18, Arm A / Arm B), 50 percent in Arm A and 67 percent in Arm B achieved a confirmed intracranial objective response by IRC assessment; median duration of intracranial response was not reached in Arm A and was 16.6 months in Arm B.
- In patients with any brain metastases at baseline the median intracranial PFS as assessed by the IRC was 12.8 months in Arm A and 18.4 months in Arm B.
- The most common grade ≥3 treatment-related adverse events (AEs) (Arm A / Arm B) included increased blood creatine phosphokinase (3 percent / 11 percent), hypertension (4 percent / 4 percent), increased lipase (4 percent / 4 percent), pneumonitis (2 percent / 4 percent), and rash (1 percent / 4 percent). Dose reduction (9 percent / 30 percent) or discontinuation (4 percent / 11 percent) due to any AEs was reported.
- The efficacy and safety data from the ALTA trial continue to support future trials with the 180 mg dosing regimen.
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). Investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 was the primary endpoint. Secondary endpoints included IRC-assessed ORR, duration of response (DOR), intracranial ORR, intracranial PFS, safety and tolerability.
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. In April of 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.
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.
To learn more about ALUNBRIG, please visit www.ALUNBRIG.com or call 1-844-A1POINT (1-844-217-6468). For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 19
