By Andrea: http://nursingoncologyjob.com
Infinity Pharmaceuticals, Inc.(INFI) announced that results from its Phase 2 study of IPI-504, a novel IV-administered Hsp90 chaperone inhibitor, in patients with advanced non-small cell lung cancer (NSCLC) were published in the Journal of Clinical Oncology (Sequist et. al., J Clin Oncol. doi: 10.1200/JCO.2010.30.8338, 2010). These data, presented previously at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO), documented for the first time the activity of an Hsp90 inhibitor in a molecularly defined cohort of patients with advanced NSCLC. In the study, IPI-504 was generally well tolerated and demonstrated clinical activity, particularly among patients with oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements.
"These results support molecular analysis as a key tool in clinical trials to determine the signature of the best responding patients, and suggest that patients with NSCLC and ALK rearrangements may preferentially respond to Hsp90 chaperone inhibition," stated Lecia Sequist, M.D., MPH, from the Massachusetts General Hospital Cancer Center and an Assistant Professor of Medicine at Harvard Medical School. "We hope the ongoing study of IPI-504 in NSCLC patients with ALK rearrangements will validate these initial findings."
"We are encouraged that IPI-504 was generally well tolerated and demonstrated clinical activity in NSCLC, further supporting the clinical potential of Hsp90 chaperone inhibition as a targeted approach to treating certain cancers," stated Julian Adams, Ph.D., president of research and development, Infinity. "The results of the ongoing Phase 1b study of IPI-504 in combination with Taxotere(R) in patients with solid tumors, as well as data from Dr. Sequist's study assessing IPI-504 in patients with NSCLC and ALK rearrangements, will help inform the path forward for IPI-504."
Trial Design and Results
The Phase 2 study of IPI-504 was designed to evaluate the safety, tolerability and anti-tumor activity of IPI-504 in patients with stage IIIb/IV NSCLC whose tumors had progressed after treatment with an EGFR tyrosine kinase inhibitor. Seventy-six patients were enrolled and stratified by their EGFR mutation status. A subset of patients also underwent EGFR (n = 25), KRAS (n = 30) and BRAF (n = 5) genotyping analysis, as well as a fluorescent in situ hybridization (FISH) assay to detect ALK gene rearrangements.
The results of the Phase 2 study show an objective response rate of seven percent in the overall study population: ten percent in patients who were EGFR wild-type, four percent in those with EGFR mutations, and 12 percent among KRAS wild-type patients. There was a 67 percent response rate among the patients with ALK rearrangements, with two of three patients experiencing partial responses and the third patient experiencing a 24 percent disease reduction. All three patients with ALK rearrangements received IPI-504 for at least six months.
IPI-504 was generally well-tolerated in this study. Most adverse events were Grade 1 or Grade 2. The most commonly reported adverse events (regardless of relationship to drug) were fatigue, nausea, diarrhea, vomiting and cough.
Showing posts with label trial cancer drugs. Show all posts
Showing posts with label trial cancer drugs. Show all posts
Saturday, October 16, 2010
Ariad Pharmaceuticals Inc. : Myeloid Leukemia and Lymphoblastic Leukemia Update
By Andrea: http://nursingoncologyjob.com
Ariad Pharmaceuticals Inc. (ARIA) recently announced the initiation of the pivotal Phase 2 clinical trial of its investigational pan-BCR-ABL inhibitor, ponatinib (previously known as AP24534), in patients with resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL). The PACE (Ponatinib Ph+ ALL and CML Evaluation) trial is designed to provide definitive clinical data for regulatory approval of ponatinib in this setting. Ponatinib has been granted orphan drug status in both the United States and Europe for the treatment of CML and Ph+ ALL.
"The start of the pivotal PACE trial represents an important step in the development of our second molecularly targeted cancer therapy," stated Harvey J. Berger, M.D., chairman and chief executive officer. "With the strong clinical evidence observed to date of hematologic, cytogenetic and molecular anti-leukemia activity of ponatinib in heavily pretreated patients with CML, including those patients with the T315I mutation for whom no current treatments are available, we are highly optimistic about the likelihood of success for ponatinib in this registration trial. We also believe that the time to full patient enrollment in this study and to potential regulatory approval of ponatinib will be swift."
Trial Design
The PACE trial is a global, single-arm clinical study of oral ponatinib in 320 patients with chronic phase, accelerated phase, or blast phase CML, as well as Ph+ ALL. Patients resistant or intolerant to dasatinib (Sprycel(R)) or nilotinib (Tasigna(R)), or with T315I mutation of BCR-ABL, will be enrolled in the trial. Patients will be grouped into one of six separate cohorts based on their phase of CML (i.e., chronic, accelerated or blast) and BCR-ABL mutation status (i.e., with or without the T315I mutation); Ph+ ALL patients will be grouped with blast phase CML. A total of 160 patients with chronic phase CML will be included. The primary endpoints are major cytogenetic response rate for chronic phase patients and major hematologic response rate for accelerated or blast phase CML patients and Ph+ ALL patients. Secondary endpoints in the trial include major molecular response rate, duration of response, progression-free survival, and overall survival.
Patients will receive ponatinib in tablet form once daily at a dose of 45 mg. The PACE trial will be conducted at approximately sixty centers in North America, Europe, Australia and Asia. Full patient enrollment is anticipated by year-end 2011.
"Clinical results from the ongoing Phase 1 trial of ponatinib, taken together with the preclinical data that characterize ponatinib as a potent, pan-BCR-ABL inhibitor, provide a strong rationale for advancing directly to a pivotal trial of ponatinib in a population of patients who have extremely limited, if any, treatment options," stated Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center and a leading investigator in the PACE trial. "There is great interest in the PACE trial from clinicians and patients, and I look forward to having this investigational option available for patients with this disease."
Regulatory Agency Agreement on Study Design
The PACE trial protocol was developed in consultation with leading CML experts from around the world. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) provided valuable input on the design and analysis of the pivotal trial. Based on these favorable interactions and depending on the actual results of this pivotal trial, ARIAD anticipates that it will be able to submit data from this single-arm trial with six months of follow-up response data.
All patients in the PACE trial will be genotyped in a central laboratory upon enrollment in the study to determine their BCR-ABL mutation status. Direct sequencing for determination of the T315I mutation will be applied rigorously and uniformly throughout the study. In parallel, ARIAD is proceeding with plans to have a companion diagnostic test for the T315I mutation developed and commercialized. The need for a commercialized companion diagnostic test in the United States applies only to the T315I cohorts and not to the larger resistant/intolerant CML patient population.
"We will use the same diagnostic test to determine T315I mutation status in the PACE trial that we used in the Phase 1 clinical trial of ponatinib, performed at a single site and applied uniformly," stated Frank G. Haluska, M.D., Ph.D., vice president and chief medical officer at ARIAD. "We have agreement with the FDA on how to proceed with genotypic evaluation of all patients in the PACE trial and will finalize plans for development and commercialization of the companion diagnostic as the PACE trial moves ahead."
Ariad Pharmaceuticals Inc. (ARIA) recently announced the initiation of the pivotal Phase 2 clinical trial of its investigational pan-BCR-ABL inhibitor, ponatinib (previously known as AP24534), in patients with resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL). The PACE (Ponatinib Ph+ ALL and CML Evaluation) trial is designed to provide definitive clinical data for regulatory approval of ponatinib in this setting. Ponatinib has been granted orphan drug status in both the United States and Europe for the treatment of CML and Ph+ ALL.
"The start of the pivotal PACE trial represents an important step in the development of our second molecularly targeted cancer therapy," stated Harvey J. Berger, M.D., chairman and chief executive officer. "With the strong clinical evidence observed to date of hematologic, cytogenetic and molecular anti-leukemia activity of ponatinib in heavily pretreated patients with CML, including those patients with the T315I mutation for whom no current treatments are available, we are highly optimistic about the likelihood of success for ponatinib in this registration trial. We also believe that the time to full patient enrollment in this study and to potential regulatory approval of ponatinib will be swift."
Trial Design
The PACE trial is a global, single-arm clinical study of oral ponatinib in 320 patients with chronic phase, accelerated phase, or blast phase CML, as well as Ph+ ALL. Patients resistant or intolerant to dasatinib (Sprycel(R)) or nilotinib (Tasigna(R)), or with T315I mutation of BCR-ABL, will be enrolled in the trial. Patients will be grouped into one of six separate cohorts based on their phase of CML (i.e., chronic, accelerated or blast) and BCR-ABL mutation status (i.e., with or without the T315I mutation); Ph+ ALL patients will be grouped with blast phase CML. A total of 160 patients with chronic phase CML will be included. The primary endpoints are major cytogenetic response rate for chronic phase patients and major hematologic response rate for accelerated or blast phase CML patients and Ph+ ALL patients. Secondary endpoints in the trial include major molecular response rate, duration of response, progression-free survival, and overall survival.
Patients will receive ponatinib in tablet form once daily at a dose of 45 mg. The PACE trial will be conducted at approximately sixty centers in North America, Europe, Australia and Asia. Full patient enrollment is anticipated by year-end 2011.
"Clinical results from the ongoing Phase 1 trial of ponatinib, taken together with the preclinical data that characterize ponatinib as a potent, pan-BCR-ABL inhibitor, provide a strong rationale for advancing directly to a pivotal trial of ponatinib in a population of patients who have extremely limited, if any, treatment options," stated Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center and a leading investigator in the PACE trial. "There is great interest in the PACE trial from clinicians and patients, and I look forward to having this investigational option available for patients with this disease."
Regulatory Agency Agreement on Study Design
The PACE trial protocol was developed in consultation with leading CML experts from around the world. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) provided valuable input on the design and analysis of the pivotal trial. Based on these favorable interactions and depending on the actual results of this pivotal trial, ARIAD anticipates that it will be able to submit data from this single-arm trial with six months of follow-up response data.
All patients in the PACE trial will be genotyped in a central laboratory upon enrollment in the study to determine their BCR-ABL mutation status. Direct sequencing for determination of the T315I mutation will be applied rigorously and uniformly throughout the study. In parallel, ARIAD is proceeding with plans to have a companion diagnostic test for the T315I mutation developed and commercialized. The need for a commercialized companion diagnostic test in the United States applies only to the T315I cohorts and not to the larger resistant/intolerant CML patient population.
"We will use the same diagnostic test to determine T315I mutation status in the PACE trial that we used in the Phase 1 clinical trial of ponatinib, performed at a single site and applied uniformly," stated Frank G. Haluska, M.D., Ph.D., vice president and chief medical officer at ARIAD. "We have agreement with the FDA on how to proceed with genotypic evaluation of all patients in the PACE trial and will finalize plans for development and commercialization of the companion diagnostic as the PACE trial moves ahead."
Subscribe to:
Posts (Atom)
