– If Approved by the European Medicines Agency, ALUNBRIG Would Become an Important First-Line Treatment Option for ALK+ NSCLC Patients
– Positive Opinion is Based on Data from Phase 3 ALTA-1L Trial, in which ALUNBRIG Demonstrated Superiority in both Overall and Intracranial Efficacy Compared to Crizotinib
CAMBRIDGE, MA, USA and OSAKA, Japan I March 2, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of ALUNBRIG (brigatinib) as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. ALUNBRIG is a next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit ALK genetic alterations.
“Because of the complex nature of ALK+ NSCLC and the way in which the disease often spreads to the brain, it is essential for physicians to have treatment options that demonstrate both overall and intracranial effectiveness,” said Professor Sanjay Popat, Consultant Medical Oncologist, Royal Marsden NHS Foundation Trust. “In the ALTA-1L trial, brigatinib demonstrated significant responses in the brain and consistent overall efficacy compared to crizotinib. If approved by the EMA, brigatinib has the potential to become an important option for the first-line treatment of ALK+ advanced NSCLC patients in Europe.”
This opinion is based on data from the Phase 3 ALTA-1L trial, which is evaluating the safety and efficacy of ALUNBRIG compared to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Results from the trial showed ALUNBRIG demonstrated superiority compared to crizotinib with significant responses observed in patients with baseline brain metastases. After more than two years of follow-up, ALUNBRIG reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (hazard ratio [HR] = 0.31, 95% CI: 0.17–0.56), as assessed by a blinded independent review committee (BIRC), and 76% (HR = 0.24, 95% CI: 0.12–0.45), as assessed by investigators. ALUNBRIG also demonstrated consistent overall efficacy (intent to treat population), with a median progression-free survival (PFS) more than two times longer than that with crizotinib at 24.0 months (95% CI: 18.5–NE) versus 11.0 months (95% CI: 9.2–12.9) for crizotinib, as assessed by BIRC, and 29.4 months (95% CI: 21.2–NE) versus 9.2 months (95% CI: 7.4–12.9), as assessed by investigators.
The safety profile of ALUNBRIG in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC). The most common treatment-emergent adverse events (TEAEs) Grade ≥3 in the ALUNBRIG arm were increased CPK (24.3%), increased lipase (14.0%) and hypertension (11.8%); and for crizotinib were increased ALT (10.2%), increased AST (6.6%), and increased lipase (6.6%).
“Developing safe and effective treatment options for cancer is a top priority for Takeda, and we continue to look for ways to address the unmet needs of the lung cancer community,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “Today’s positive CHMP opinion is an important step towards bringing ALUNBRIG to people living with ALK+ advanced NSCLC, and we look forward to continuing to work with the EMA as they review the application for ALUNBRIG as a first-line treatment of patients with this serious and rare form of lung cancer.”
“ALK+ NSCLC is a rarer form of lung cancer, and the needs of people impacted by it are multiple,” said Stefania Vallone, President of Lung Cancer Europe (LuCE). “Despite progress in recent years, there remains a need for additional first-line treatment options for the approximately 10,000 people with ALK+ NSCLC in Europe.”
The positive opinion for ALUNBRIG will now be reviewed by the European Commission (EC) for Commission Decision. ALUNBRIG is currently not approved as a therapy for first-line ALK+ NSCLC.
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 (ALUNBRIG, n=137, crizotinib, n=138) 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.
The median age was 58 years in the ALUNBRIG arm and 60 years in the crizotinib arm. Twenty-nine percent of patients had brain metastases at baseline in the ALUNBRIG arm versus 30% in the crizotinib arm. Twenty-six percent of patients received prior chemotherapy for advanced or metastatic disease in the ALUNBRIG arm versus 27% in the crizotinib arm.
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.
The safety profile of ALUNBRIG in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC).
About ALUNBRIG® (brigatinib)
ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit anaplastic lymphoma kinase (ALK) genetic alterations. In April 2017, ALUNBRIG received Accelerated Approval from the U.S. 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 is currently approved in more than 40 countries, including the U.S., Canada and the European Union, for the treatment of people living with ALK+ metastatic NSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib.
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.
About ALK+ NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.1,2 Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients.3 Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.4,5,6
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.7
Takeda’s Commitment to Lung Cancer
Takeda is dedicated to expanding treatment options in the ALK+ NSCLC and EGFR/HER2 mutant NSCLC treatment landscapes. Our comprehensive programs include the following clinical trials to continue to address unmet needs for people living with lung cancer:
ALUNBRIG
- Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG. This trial has completed enrollment.
- 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. This trial has completed enrollment.
- Phase 3 ALTA-1L, 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. This trial has completed enrollment.
- Phase 2 J-ALTA, single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib. This trial has completed enrollment.
- Phase 2 ALTA 2, global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib. This trial has completed enrollment.
- Phase 3 ALTA 3, global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib. This trial is now enrolling.
TAK-788, a selective inhibitor of EGFR/HER2 mutations, currently being explored in EGFR exon 20 insertion mutations:
- Phase 1/2 study evaluating the safety, pharmacokinetics and antitumor activity of oral EGFR/HER2 inhibitor TAK-788 in patients with NSCLC. This trial has completed enrollment.
- Phase 2 EXCLAIM, pivotal extension cohort of the Phase 1/2 trial, which was designed to evaluate the efficacy and safety of TAK-788 at 160 mg once daily in previously treated patients with EGFR exon 20 insertion mutations. This trial has completed enrollment.
- Phase 3 EXCLAIM 2, global, randomized study evaluating the efficacy of TAK-788 as a first-line treatment compared to platinum-based doublet chemotherapy in treatment-naïve patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
- Phase 1, open-label, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of TAK-788 in Japanese patients with locally advanced or metastatic NSCLC. This trial has completed enrollment.
- Phase 2 J-EXCLAIM, open-label, multicenter, study evaluating the efficacy of TAK-788 as a first-line treatment in Japanese patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
- Phase 1, open-label, two-period, fixed-sequence study designed to characterize drug-drug interaction between TAK-788 and either a strong cytochrome P-450 (CYP)3A inhibitor, itraconazole (Part 1) or a strong CYP3A inducer, rifampin (Part 2) in healthy adult subjects. This trial is now enrolling.
For additional information on the ALUNBRIG and TAK-788 clinical trials, please visit www.clinicaltrials.gov
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.
For more information, visit https://www.takeda.com.
1 World Health Organization. Latest Global Cancer Data. https://www.who.int/cancer/PRGlobocanFinal.pdf. Accessed May 11, 2019.
2 American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed May 11, 2019.
3 Kris MG, et al. JAMA, 2014;311:1998-2006.
4 Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-81.
5 Koivunen JP, Mermel C, Zejnullahu K, et al. Clin Cancer Res. 2008; 14(13):4275-83.
6 Wong DW, Leung EL, So KK, et al. Cancer. 2009; 115(8):1723-33.
7 Chia PL, Mitchell P, Dobrovic A, John T. Clin Epidemiol, 2014;6:423-432.
SOURCE: Takeda Pharmaceutical Co
Post Views: 24
– If Approved by the European Medicines Agency, ALUNBRIG Would Become an Important First-Line Treatment Option for ALK+ NSCLC Patients
– Positive Opinion is Based on Data from Phase 3 ALTA-1L Trial, in which ALUNBRIG Demonstrated Superiority in both Overall and Intracranial Efficacy Compared to Crizotinib
CAMBRIDGE, MA, USA and OSAKA, Japan I March 2, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of ALUNBRIG (brigatinib) as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. ALUNBRIG is a next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit ALK genetic alterations.
“Because of the complex nature of ALK+ NSCLC and the way in which the disease often spreads to the brain, it is essential for physicians to have treatment options that demonstrate both overall and intracranial effectiveness,” said Professor Sanjay Popat, Consultant Medical Oncologist, Royal Marsden NHS Foundation Trust. “In the ALTA-1L trial, brigatinib demonstrated significant responses in the brain and consistent overall efficacy compared to crizotinib. If approved by the EMA, brigatinib has the potential to become an important option for the first-line treatment of ALK+ advanced NSCLC patients in Europe.”
This opinion is based on data from the Phase 3 ALTA-1L trial, which is evaluating the safety and efficacy of ALUNBRIG compared to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Results from the trial showed ALUNBRIG demonstrated superiority compared to crizotinib with significant responses observed in patients with baseline brain metastases. After more than two years of follow-up, ALUNBRIG reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (hazard ratio [HR] = 0.31, 95% CI: 0.17–0.56), as assessed by a blinded independent review committee (BIRC), and 76% (HR = 0.24, 95% CI: 0.12–0.45), as assessed by investigators. ALUNBRIG also demonstrated consistent overall efficacy (intent to treat population), with a median progression-free survival (PFS) more than two times longer than that with crizotinib at 24.0 months (95% CI: 18.5–NE) versus 11.0 months (95% CI: 9.2–12.9) for crizotinib, as assessed by BIRC, and 29.4 months (95% CI: 21.2–NE) versus 9.2 months (95% CI: 7.4–12.9), as assessed by investigators.
The safety profile of ALUNBRIG in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC). The most common treatment-emergent adverse events (TEAEs) Grade ≥3 in the ALUNBRIG arm were increased CPK (24.3%), increased lipase (14.0%) and hypertension (11.8%); and for crizotinib were increased ALT (10.2%), increased AST (6.6%), and increased lipase (6.6%).
“Developing safe and effective treatment options for cancer is a top priority for Takeda, and we continue to look for ways to address the unmet needs of the lung cancer community,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “Today’s positive CHMP opinion is an important step towards bringing ALUNBRIG to people living with ALK+ advanced NSCLC, and we look forward to continuing to work with the EMA as they review the application for ALUNBRIG as a first-line treatment of patients with this serious and rare form of lung cancer.”
“ALK+ NSCLC is a rarer form of lung cancer, and the needs of people impacted by it are multiple,” said Stefania Vallone, President of Lung Cancer Europe (LuCE). “Despite progress in recent years, there remains a need for additional first-line treatment options for the approximately 10,000 people with ALK+ NSCLC in Europe.”
The positive opinion for ALUNBRIG will now be reviewed by the European Commission (EC) for Commission Decision. ALUNBRIG is currently not approved as a therapy for first-line ALK+ NSCLC.
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 (ALUNBRIG, n=137, crizotinib, n=138) 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.
The median age was 58 years in the ALUNBRIG arm and 60 years in the crizotinib arm. Twenty-nine percent of patients had brain metastases at baseline in the ALUNBRIG arm versus 30% in the crizotinib arm. Twenty-six percent of patients received prior chemotherapy for advanced or metastatic disease in the ALUNBRIG arm versus 27% in the crizotinib arm.
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.
The safety profile of ALUNBRIG in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC).
About ALUNBRIG® (brigatinib)
ALUNBRIG is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit anaplastic lymphoma kinase (ALK) genetic alterations. In April 2017, ALUNBRIG received Accelerated Approval from the U.S. 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 is currently approved in more than 40 countries, including the U.S., Canada and the European Union, for the treatment of people living with ALK+ metastatic NSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib.
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.
About ALK+ NSCLC
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.1,2 Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients.3 Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.4,5,6
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.7
Takeda’s Commitment to Lung Cancer
Takeda is dedicated to expanding treatment options in the ALK+ NSCLC and EGFR/HER2 mutant NSCLC treatment landscapes. Our comprehensive programs include the following clinical trials to continue to address unmet needs for people living with lung cancer:
ALUNBRIG
- Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG. This trial has completed enrollment.
- 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. This trial has completed enrollment.
- Phase 3 ALTA-1L, 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. This trial has completed enrollment.
- Phase 2 J-ALTA, single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib. This trial has completed enrollment.
- Phase 2 ALTA 2, global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib. This trial has completed enrollment.
- Phase 3 ALTA 3, global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib. This trial is now enrolling.
TAK-788, a selective inhibitor of EGFR/HER2 mutations, currently being explored in EGFR exon 20 insertion mutations:
- Phase 1/2 study evaluating the safety, pharmacokinetics and antitumor activity of oral EGFR/HER2 inhibitor TAK-788 in patients with NSCLC. This trial has completed enrollment.
- Phase 2 EXCLAIM, pivotal extension cohort of the Phase 1/2 trial, which was designed to evaluate the efficacy and safety of TAK-788 at 160 mg once daily in previously treated patients with EGFR exon 20 insertion mutations. This trial has completed enrollment.
- Phase 3 EXCLAIM 2, global, randomized study evaluating the efficacy of TAK-788 as a first-line treatment compared to platinum-based doublet chemotherapy in treatment-naïve patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
- Phase 1, open-label, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of TAK-788 in Japanese patients with locally advanced or metastatic NSCLC. This trial has completed enrollment.
- Phase 2 J-EXCLAIM, open-label, multicenter, study evaluating the efficacy of TAK-788 as a first-line treatment in Japanese patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
- Phase 1, open-label, two-period, fixed-sequence study designed to characterize drug-drug interaction between TAK-788 and either a strong cytochrome P-450 (CYP)3A inhibitor, itraconazole (Part 1) or a strong CYP3A inducer, rifampin (Part 2) in healthy adult subjects. This trial is now enrolling.
For additional information on the ALUNBRIG and TAK-788 clinical trials, please visit www.clinicaltrials.gov
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.
For more information, visit https://www.takeda.com.
1 World Health Organization. Latest Global Cancer Data. https://www.who.int/cancer/PRGlobocanFinal.pdf. Accessed May 11, 2019.
2 American Cancer Society. What is Non-Small Cell Lung Cancer? https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed May 11, 2019.
3 Kris MG, et al. JAMA, 2014;311:1998-2006.
4 Gainor JF, Varghese AM, Ou SH, et al. Clin Cancer Res. 2013;19(15):4273-81.
5 Koivunen JP, Mermel C, Zejnullahu K, et al. Clin Cancer Res. 2008; 14(13):4275-83.
6 Wong DW, Leung EL, So KK, et al. Cancer. 2009; 115(8):1723-33.
7 Chia PL, Mitchell P, Dobrovic A, John T. Clin Epidemiol, 2014;6:423-432.
SOURCE: Takeda Pharmaceutical Co
Post Views: 24
