– In Patients with Brain Metastases at Baseline, ALUNBRIG Reduced the Risk of Progression in the Brain or Death by 73 Percent –
– Intracranial Efficacy Data Reinforces Superiority of ALUNBRIG Versus Crizotinib in the First-Line Treatment Setting –
– Data Will Be Presented in a Poster Discussion at the European Society for Medical Oncology 2018 Congress on Friday, October 19 –
CAMBRIDGE, MA, USA & OSAKA, Japan I October 19, 2018 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that intracranial efficacy data from the Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial showed improved intracranial progression-free survival (PFS) and intracranial objective response rate (ORR) with ALUNBRIG (brigatinib) compared to crizotinib among anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) patients. Data for these secondary endpoints will be presented in a poster discussion at the European Society for Medical Oncology (ESMO) 2018 Congress on Friday, October 19 at 2:00 p.m. CET in Munich, Germany. These results further support ALUNBRIG as a potential treatment for adults with ALK+ locally advanced or metastatic NSCLC who had not received a prior ALK inhibitor. ALUNBRIG is currently not approved as first-line therapy for advanced ALK+ NSCLC.
“ALK+ NSCLC often spreads to the brain, so having options that can clearly demonstrate efficacy both in the brain and systemically is important for physicians and their patients,” said Sanjay Popat, PhD, FRCP, Medical Oncologist, Royal Marsden Hospital. “The ALTA-1L trial showed that treatment with brigatinib significantly delayed progression of disease in the brain compared to crizotinib, and we look forward to sharing the clinical evidence with the medical community at ESMO.”
In the first interim analysis of the ALTA-1L trial, intracranial PFS was significantly improved with ALUNBRIG compared to crizotinib in the Intention to Treat population (ITT) (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.24−0.70; log-rank P=0.0006) and the population with baseline brain metastases (HR: 0.27, 95% CI: 0.13−0.54; log-rank P<0.0001). Among patients with brain metastases at baseline, ALUNBRIG reduced the risk of progression in the brain or death by 73 percent. Intracranial PFS in patients without brain metastases at baseline is not yet mature as of this first interim analysis.
Treatment with ALUNBRIG also demonstrated an improved intracranial ORR compared to crizotinib. For patients with measurable brain metastases at baseline, 78 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 29 percent in the crizotinib arm. For patients with non-measurable brain metastases at baseline, 67 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 17 percent in the crizotinib arm.
In addition, ALUNBRIG significantly delayed both central nervous system (CNS) progression (without prior systemic progression) and systemic progression (without prior CNS progression) compared to crizotinib. Baseline factors related to the CNS, such as the proportion of patients with baseline brain metastases, mean number of brain metastases, and prior brain radiotherapy, including type, were balanced among patients in the two study arms. The safety profile associated with ALUNBRIG in the ALTA-1L trial was generally consistent with the existing U.S. prescribing information.
“CNS disease presents a significant burden for patients with ALK+ NSCLC,” said David Kerstein, MD, Global Clinical Lead for Brigatinib and Lung Cancer Clinical Portfolio Strategy Lead, Takeda. “These additional intracranial efficacy results from the ALTA-1L trial build upon activity previously reported with ALUNBRIG in patients with brain metastases in the post-crizotinib setting and demonstrate Takeda’s dedication to research that aims to improve outcomes for those living with this serious disease.”
These data build on results recently presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC), which showed that treatment with ALUNBRIG resulted in superior PFS compared to crizotinib as assessed by a blinded independent review committee, corresponding to a 51 percent reduction in the risk of disease progression or death (HR: 0.49, 95% CI: 0.33−0.74]; log-rank P=0.0007).
Grade 3 to 5 treatment-emergent adverse events occurred in 61% of the patients in the brigatinib arm and 55% of the patients in the crizotinib arm. Most common grade 3 or greater treatment-emergent adverse events for brigatinib were increased blood creatine phosphokinase (16%), increased lipase (13%), hypertension (10%), and increased amylase (5%); and for crizotinib were increased alanine aminotransferase (9%), increased aspartate aminotransferase (6%), and increased lipase (5%).
About the ALTA-1L Trial
The Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st 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. Blinded Independent Review Committee (BIRC)-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 approximately 50 percent of planned PFS events and one at approximately 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. In July 2018, Health Canada approved ALUNBRIG for the treatment of adult patients with ALK+ metastatic NSCLC who have progressed on or who were intolerant to an ALK inhibitor (crizotinib). The FDA and Health Canada approvals of ALUNBRIG were primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) 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.
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, a global randomized 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 trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
- Phase 2 global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
- Phase 3 global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib
For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 9
– In Patients with Brain Metastases at Baseline, ALUNBRIG Reduced the Risk of Progression in the Brain or Death by 73 Percent –
– Intracranial Efficacy Data Reinforces Superiority of ALUNBRIG Versus Crizotinib in the First-Line Treatment Setting –
– Data Will Be Presented in a Poster Discussion at the European Society for Medical Oncology 2018 Congress on Friday, October 19 –
CAMBRIDGE, MA, USA & OSAKA, Japan I October 19, 2018 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that intracranial efficacy data from the Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial showed improved intracranial progression-free survival (PFS) and intracranial objective response rate (ORR) with ALUNBRIG (brigatinib) compared to crizotinib among anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) patients. Data for these secondary endpoints will be presented in a poster discussion at the European Society for Medical Oncology (ESMO) 2018 Congress on Friday, October 19 at 2:00 p.m. CET in Munich, Germany. These results further support ALUNBRIG as a potential treatment for adults with ALK+ locally advanced or metastatic NSCLC who had not received a prior ALK inhibitor. ALUNBRIG is currently not approved as first-line therapy for advanced ALK+ NSCLC.
“ALK+ NSCLC often spreads to the brain, so having options that can clearly demonstrate efficacy both in the brain and systemically is important for physicians and their patients,” said Sanjay Popat, PhD, FRCP, Medical Oncologist, Royal Marsden Hospital. “The ALTA-1L trial showed that treatment with brigatinib significantly delayed progression of disease in the brain compared to crizotinib, and we look forward to sharing the clinical evidence with the medical community at ESMO.”
In the first interim analysis of the ALTA-1L trial, intracranial PFS was significantly improved with ALUNBRIG compared to crizotinib in the Intention to Treat population (ITT) (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.24−0.70; log-rank P=0.0006) and the population with baseline brain metastases (HR: 0.27, 95% CI: 0.13−0.54; log-rank P<0.0001). Among patients with brain metastases at baseline, ALUNBRIG reduced the risk of progression in the brain or death by 73 percent. Intracranial PFS in patients without brain metastases at baseline is not yet mature as of this first interim analysis.
Treatment with ALUNBRIG also demonstrated an improved intracranial ORR compared to crizotinib. For patients with measurable brain metastases at baseline, 78 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 29 percent in the crizotinib arm. For patients with non-measurable brain metastases at baseline, 67 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 17 percent in the crizotinib arm.
In addition, ALUNBRIG significantly delayed both central nervous system (CNS) progression (without prior systemic progression) and systemic progression (without prior CNS progression) compared to crizotinib. Baseline factors related to the CNS, such as the proportion of patients with baseline brain metastases, mean number of brain metastases, and prior brain radiotherapy, including type, were balanced among patients in the two study arms. The safety profile associated with ALUNBRIG in the ALTA-1L trial was generally consistent with the existing U.S. prescribing information.
“CNS disease presents a significant burden for patients with ALK+ NSCLC,” said David Kerstein, MD, Global Clinical Lead for Brigatinib and Lung Cancer Clinical Portfolio Strategy Lead, Takeda. “These additional intracranial efficacy results from the ALTA-1L trial build upon activity previously reported with ALUNBRIG in patients with brain metastases in the post-crizotinib setting and demonstrate Takeda’s dedication to research that aims to improve outcomes for those living with this serious disease.”
These data build on results recently presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC), which showed that treatment with ALUNBRIG resulted in superior PFS compared to crizotinib as assessed by a blinded independent review committee, corresponding to a 51 percent reduction in the risk of disease progression or death (HR: 0.49, 95% CI: 0.33−0.74]; log-rank P=0.0007).
Grade 3 to 5 treatment-emergent adverse events occurred in 61% of the patients in the brigatinib arm and 55% of the patients in the crizotinib arm. Most common grade 3 or greater treatment-emergent adverse events for brigatinib were increased blood creatine phosphokinase (16%), increased lipase (13%), hypertension (10%), and increased amylase (5%); and for crizotinib were increased alanine aminotransferase (9%), increased aspartate aminotransferase (6%), and increased lipase (5%).
About the ALTA-1L Trial
The Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st 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. Blinded Independent Review Committee (BIRC)-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 approximately 50 percent of planned PFS events and one at approximately 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. In July 2018, Health Canada approved ALUNBRIG for the treatment of adult patients with ALK+ metastatic NSCLC who have progressed on or who were intolerant to an ALK inhibitor (crizotinib). The FDA and Health Canada approvals of ALUNBRIG were primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) 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.
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, a global randomized 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 trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
- Phase 2 global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
- Phase 3 global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib
For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 9
