– ALUNBRIG has Potential to Expand its Indication in ALK+ Metastatic Non-Small Cell Lung Cancer
– Prescription Drug User Fee Act (PDUFA) Target Action Date Set for June 23, 2020
CAMBRIDGE, MA, USA and OSAKA, Japan I February 24, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has granted priority review for the company’s supplemental New Drug Application (sNDA) to expand the use of ALUNBRIG (brigatinib) as a first-line treatment for patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ALUNBRIG is a next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit ALK genetic alterations.
“ALK+ NSCLC is a rare and serious form of lung cancer that is complex to treat. While progress has been made, unmet needs still exist for the approximately 40,000 patients diagnosed with this disease worldwide each year,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “This is an important first step in expanding treatment options for people with ALK+ metastatic NSCLC in the U.S., and we look forward to continuing to work with regulatory authorities around the world to bring ALUNBRIG to newly diagnosed patients.”
The sNDA for ALUNBRIG as a first-line treatment is based on results from the Phase 3 ALTA-1L trial, which is evaluating the safety and efficacy of ALUNBRIG in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor compared to that of crizotinib in the same population. The ALTA-1L trial met its primary endpoint with ALUNBRIG demonstrating superiority in blinded independent review committee (BIRC)-assessed progression-free survival (PFS) compared to crizotinib.
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 U.S. prescribing information.
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
- 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
- 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
Post Views: 85
– ALUNBRIG has Potential to Expand its Indication in ALK+ Metastatic Non-Small Cell Lung Cancer
– Prescription Drug User Fee Act (PDUFA) Target Action Date Set for June 23, 2020
CAMBRIDGE, MA, USA and OSAKA, Japan I February 24, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has granted priority review for the company’s supplemental New Drug Application (sNDA) to expand the use of ALUNBRIG (brigatinib) as a first-line treatment for patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ALUNBRIG is a next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit ALK genetic alterations.
“ALK+ NSCLC is a rare and serious form of lung cancer that is complex to treat. While progress has been made, unmet needs still exist for the approximately 40,000 patients diagnosed with this disease worldwide each year,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “This is an important first step in expanding treatment options for people with ALK+ metastatic NSCLC in the U.S., and we look forward to continuing to work with regulatory authorities around the world to bring ALUNBRIG to newly diagnosed patients.”
The sNDA for ALUNBRIG as a first-line treatment is based on results from the Phase 3 ALTA-1L trial, which is evaluating the safety and efficacy of ALUNBRIG in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor compared to that of crizotinib in the same population. The ALTA-1L trial met its primary endpoint with ALUNBRIG demonstrating superiority in blinded independent review committee (BIRC)-assessed progression-free survival (PFS) compared to crizotinib.
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 U.S. prescribing information.
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
- 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
- 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
Post Views: 85
