Phase 2 PINNACLE Study in Small Cell Lung Cancer Continues Following DSMB and FDA Review
REDWOOD CITY, CA, USA I February 08, 2016 I OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, announced updates on the tarextumab (anti-Notch 2/3, OMP-59R5) Phase 2 programs in pancreatic cancer (the “ALPINE” study) and small cell lung cancer (the “PINNACLE” study). OncoMed will continue the PINNACLE Phase 2 trial of tarextumab in small cell lung cancer following a review of unblinded safety and efficacy data from both the ALPINE and PINNACLE studies by the U.S. Food and Drug Administration (FDA) and the PINNACLE Data Safety Monitoring Board (DSMB). The PINNACLE study remains blinded to OncoMed, investigators and patients. OncoMed has discontinued dosing of tarextumab in the Phase 2 ALPINE clinical study.
“After communicating with the FDA and the PINNACLE trial DSMB we have received feedback that appropriate safety monitoring is in place to continue the PINNACLE trial,” said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. “While we remain blinded to the PINNACLE trial data, differences in pancreatic and small cell lung cancer biology, combined with our understanding of the potential mechanisms of tarextumab, give us confidence to continue the PINNACLE Phase 2 clinical trial.”
ALPINE Analysis
On January 25, OncoMed announced feedback received from a pre-planned DSMB analysis of the ALPINE Phase 2 clinical trial. Following receipt of that feedback, OncoMed promptly discontinued patient dosing in the ALPINE trial and proceeded to unblind the study. Subsequently, based on its own initial analysis of unblinded interim Phase 2 data, OncoMed confirmed key findings by the DSMB regarding futility of the ALPINE trial. Post-hoc, exploratory, and ongoing analyses conducted by OncoMed revealed subgroups of patients with decreased survival and a subgroup which appears to exhibit improved survival with tarextumab. OncoMed will continue to analyze the ALPINE data, and present the data at a future medical meeting.
“We have obtained a good understanding of the results from the ALPINE trial. We believe there are important differences in effects that are unique and specific to tarextumab inhibition of Notch signaling within different tumor types that may have significant impact on the drug’s anti-tumor activity. As such, we feel that there is evidence that tarextumab may behave differently in the small cell lung cancer setting than in the pancreatic cancer setting,” said Jakob Dupont, M.D., Chief Medical Officer. “We are encouraged that the PINNACLE study will continue after a careful assessment in collaboration with the independent DSMB, the FDA and the investigators. We hope to make a difference for patients with small cell lung cancer who are in need of new and improved therapies. We thank our tarextumab investigators, their teams, the patients, their families, and caregivers for participating in the ALPINE and PINNACLE clinical trials. Their efforts are advancing our understanding of pancreatic and small cell lung cancer treatment.”
Impact on PINNACLE
Following notification of the ALPINE DSMB’s findings, OncoMed initiated interactions with tarextumab clinical investigators, partner GlaxoSmithKline, the FDA and the PINNACLE trial’s DSMB chairperson to assess potential impact of these results on the overall development program, including the ongoing Phase 2 PINNACLE trial in small-cell lung cancer patients.
PINNACLE trial investigators received an addendum to the informed consent form that included a description of the interim analysis from ALPINE. The FDA and the PINNACLE DSMB were provided unblinded data from both Phase 2 trials, a description of OncoMed’s exploratory analysis of the ALPINE results and related trial materials for review. The independent analyses of the FDA and PINNACLE DSMB indicated that the PINNACLE trial could continue under the supervision of the PINNACLE DSMB monitoring for safety and efficacy and that appropriate safeguards are in place.
OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab for the treatment of small cell lung cancer. The randomized Phase 2 trial is comparing progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive placebo plus chemotherapy. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients. Results from the Phase 2 PINNACLE trial are anticipated in 2017.
OncoMed plans to present updated PINNACLE Phase 1b data at the 16th Annual Targeted Therapies of the Treatment of Lung Cancer in Santa Monica, California taking place February 17-20, 2016.
About Tarextumab (anti-Notch2/3, OMP-59R5)
Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment.
Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin-LGR. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate that is part of OncoMed’s collaboration with Celgene (IO#2) toward clinical trials in the 2016-2017 timeframe.
SOURCE: OncoMed Pharmaceuticals
Post Views: 33
Phase 2 PINNACLE Study in Small Cell Lung Cancer Continues Following DSMB and FDA Review
REDWOOD CITY, CA, USA I February 08, 2016 I OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, announced updates on the tarextumab (anti-Notch 2/3, OMP-59R5) Phase 2 programs in pancreatic cancer (the “ALPINE” study) and small cell lung cancer (the “PINNACLE” study). OncoMed will continue the PINNACLE Phase 2 trial of tarextumab in small cell lung cancer following a review of unblinded safety and efficacy data from both the ALPINE and PINNACLE studies by the U.S. Food and Drug Administration (FDA) and the PINNACLE Data Safety Monitoring Board (DSMB). The PINNACLE study remains blinded to OncoMed, investigators and patients. OncoMed has discontinued dosing of tarextumab in the Phase 2 ALPINE clinical study.
“After communicating with the FDA and the PINNACLE trial DSMB we have received feedback that appropriate safety monitoring is in place to continue the PINNACLE trial,” said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. “While we remain blinded to the PINNACLE trial data, differences in pancreatic and small cell lung cancer biology, combined with our understanding of the potential mechanisms of tarextumab, give us confidence to continue the PINNACLE Phase 2 clinical trial.”
ALPINE Analysis
On January 25, OncoMed announced feedback received from a pre-planned DSMB analysis of the ALPINE Phase 2 clinical trial. Following receipt of that feedback, OncoMed promptly discontinued patient dosing in the ALPINE trial and proceeded to unblind the study. Subsequently, based on its own initial analysis of unblinded interim Phase 2 data, OncoMed confirmed key findings by the DSMB regarding futility of the ALPINE trial. Post-hoc, exploratory, and ongoing analyses conducted by OncoMed revealed subgroups of patients with decreased survival and a subgroup which appears to exhibit improved survival with tarextumab. OncoMed will continue to analyze the ALPINE data, and present the data at a future medical meeting.
“We have obtained a good understanding of the results from the ALPINE trial. We believe there are important differences in effects that are unique and specific to tarextumab inhibition of Notch signaling within different tumor types that may have significant impact on the drug’s anti-tumor activity. As such, we feel that there is evidence that tarextumab may behave differently in the small cell lung cancer setting than in the pancreatic cancer setting,” said Jakob Dupont, M.D., Chief Medical Officer. “We are encouraged that the PINNACLE study will continue after a careful assessment in collaboration with the independent DSMB, the FDA and the investigators. We hope to make a difference for patients with small cell lung cancer who are in need of new and improved therapies. We thank our tarextumab investigators, their teams, the patients, their families, and caregivers for participating in the ALPINE and PINNACLE clinical trials. Their efforts are advancing our understanding of pancreatic and small cell lung cancer treatment.”
Impact on PINNACLE
Following notification of the ALPINE DSMB’s findings, OncoMed initiated interactions with tarextumab clinical investigators, partner GlaxoSmithKline, the FDA and the PINNACLE trial’s DSMB chairperson to assess potential impact of these results on the overall development program, including the ongoing Phase 2 PINNACLE trial in small-cell lung cancer patients.
PINNACLE trial investigators received an addendum to the informed consent form that included a description of the interim analysis from ALPINE. The FDA and the PINNACLE DSMB were provided unblinded data from both Phase 2 trials, a description of OncoMed’s exploratory analysis of the ALPINE results and related trial materials for review. The independent analyses of the FDA and PINNACLE DSMB indicated that the PINNACLE trial could continue under the supervision of the PINNACLE DSMB monitoring for safety and efficacy and that appropriate safeguards are in place.
OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab for the treatment of small cell lung cancer. The randomized Phase 2 trial is comparing progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive placebo plus chemotherapy. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients. Results from the Phase 2 PINNACLE trial are anticipated in 2017.
OncoMed plans to present updated PINNACLE Phase 1b data at the 16th Annual Targeted Therapies of the Treatment of Lung Cancer in Santa Monica, California taking place February 17-20, 2016.
About Tarextumab (anti-Notch2/3, OMP-59R5)
Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment.
Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin-LGR. OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK). OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate that is part of OncoMed’s collaboration with Celgene (IO#2) toward clinical trials in the 2016-2017 timeframe.
SOURCE: OncoMed Pharmaceuticals
Post Views: 33
