~Brigatinib Achieves Confirmed Response in Patient with G1202R Mutation that Emerges Following Treatment with Current Approved Therapies
CHICAGO, IL & CAMBRIDGE, MA, USA I June 4, 2016 I ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced clinical data from an analysis aimed at characterizing the activity of its investigational tyrosine kinase inhibitor (TKI), brigatinib, in patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC) who have progressed on crizotinib. The analysis was based on ALK mutation status as determined by next-generation sequencing (NGS) of tumor tissue collected from the ongoing Phase 1/2 and ALTA clinical trials.
Data from this analysis showed that brigatinib yields confirmed responses in patients with multiple different secondary ALK mutations, including one G1202R case. There are no currently approved ALK treatments that have demonstrated activity against the G1202R mutation.
These data are being presented today at the 2016 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Study Methods
Requirements for the Phase 1/2 and ALTA trials of brigatinib included that tumor tissue be collected at patient screening after failure on crizotinib therapy and prior to brigatinib treatment. An optional post-baseline tumor biopsy also was requested following disease progression on brigatinib. Tumor samples were analyzed using a NGS (next-generation sequencing) platform that examined the entire coding sequence of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. This analysis focuses on the relationship between brigatinib clinical activity and ALK mutation status at baseline and after disease progression on brigatinib therapy.
A total of 32 baseline tumor samples from the clinical trials of brigatinib were evaluable using NGS, and a total of six post-baseline samples following disease progression on brigatinib were evaluable by NGS.
Study Results
- Of the 32 patients with baseline NGS data, 22 (69%) achieved a confirmed objective response on brigatinib.
- Of the 9 patients with secondary ALK mutations at baseline, 7 (78%) achieved a confirmed objective response on brigatinib.
- Of the 23 patients without secondary ALK mutations at baseline, 15 (65%) achieved a confirmed objective response rate (ORR) on brigatinib.
- Of the 6 patients with evaluable tissue samples collected after progression on brigatinib therapy, 5 (83%) were determined to have detectable secondary mutations in the ALK kinase domain. Three out of five of these patients had complex mutation patterns, following responses lasting 5.4, 7.4 and 28.5 months. Two out of five had single secondary ALK kinase domain mutations detected, following responses lasting 10.9 and 11 months.
- Of the one patient with a secondary G1202R mutation, the patient achieved a confirmed response on brigatinib and the response is on-going.
“It is encouraging that responses to brigatinib were observed in patients with crizotinib resistant ALK+ lung cancer with and without the presence of ALK resistance mutations. This is consistent with preclinical studies showing brigatinib to be a potent pan-inhibitor of all known ALK secondary resistance mutants,” stated Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts is an orphan oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other orphan cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter @ARIADPharm).
SOURCE: Ariad Pharmaceuticals
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~Brigatinib Achieves Confirmed Response in Patient with G1202R Mutation that Emerges Following Treatment with Current Approved Therapies
CHICAGO, IL & CAMBRIDGE, MA, USA I June 4, 2016 I ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced clinical data from an analysis aimed at characterizing the activity of its investigational tyrosine kinase inhibitor (TKI), brigatinib, in patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC) who have progressed on crizotinib. The analysis was based on ALK mutation status as determined by next-generation sequencing (NGS) of tumor tissue collected from the ongoing Phase 1/2 and ALTA clinical trials.
Data from this analysis showed that brigatinib yields confirmed responses in patients with multiple different secondary ALK mutations, including one G1202R case. There are no currently approved ALK treatments that have demonstrated activity against the G1202R mutation.
These data are being presented today at the 2016 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Study Methods
Requirements for the Phase 1/2 and ALTA trials of brigatinib included that tumor tissue be collected at patient screening after failure on crizotinib therapy and prior to brigatinib treatment. An optional post-baseline tumor biopsy also was requested following disease progression on brigatinib. Tumor samples were analyzed using a NGS (next-generation sequencing) platform that examined the entire coding sequence of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. This analysis focuses on the relationship between brigatinib clinical activity and ALK mutation status at baseline and after disease progression on brigatinib therapy.
A total of 32 baseline tumor samples from the clinical trials of brigatinib were evaluable using NGS, and a total of six post-baseline samples following disease progression on brigatinib were evaluable by NGS.
Study Results
- Of the 32 patients with baseline NGS data, 22 (69%) achieved a confirmed objective response on brigatinib.
- Of the 9 patients with secondary ALK mutations at baseline, 7 (78%) achieved a confirmed objective response on brigatinib.
- Of the 23 patients without secondary ALK mutations at baseline, 15 (65%) achieved a confirmed objective response rate (ORR) on brigatinib.
- Of the 6 patients with evaluable tissue samples collected after progression on brigatinib therapy, 5 (83%) were determined to have detectable secondary mutations in the ALK kinase domain. Three out of five of these patients had complex mutation patterns, following responses lasting 5.4, 7.4 and 28.5 months. Two out of five had single secondary ALK kinase domain mutations detected, following responses lasting 10.9 and 11 months.
- Of the one patient with a secondary G1202R mutation, the patient achieved a confirmed response on brigatinib and the response is on-going.
“It is encouraging that responses to brigatinib were observed in patients with crizotinib resistant ALK+ lung cancer with and without the presence of ALK resistance mutations. This is consistent with preclinical studies showing brigatinib to be a potent pan-inhibitor of all known ALK secondary resistance mutants,” stated Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts is an orphan oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other orphan cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter @ARIADPharm).
SOURCE: Ariad Pharmaceuticals
Post Views: 76
