New ALK Inhibitor 'Fantastically Active'
Editor's Note: The lung cancers sessions at the 2013 Annual Meeting of theAmerican Society of Clinical Oncology (ASCO®) were abuzz over data on a growing number of emerging targeted therapies. H. Jack West, MD, for Medscape, spoke to David Ross Camidge, MD, PhD, Associate Professor of Oncology at Colorado University, Denver, about data he presented on a highly promising ALK inhibitor, AP26113.
Medscape: Can you tell us a bit about the drug and the study that you are presenting today?
Dr. Camidge: AP26113 is a second-generation ALK and ROS1 inhibitor that seems in vitro to also have some activity against the activating epidermal growth factor receptor (EGFR) mutations and T790M. However, it needs to achieve an order of magnitude higher concentration to be active against the EGFR targets than it does against the ALK/ROS1 targets. We are showing the results from the phase 1 dose-escalation study across a broad dose range.
In the ALK patients, most of whom have not responded to crizotinib, we are seeing fantastic activity: a 75% response rate in patients who had progressed on crizotinib. That is occurring at doses from 60 mg all the way up to 240 mg. They are now taking 180 mg forward as the recommended phase 2 dose. It seems to be very well tolerated. One case of pneumonitis occurred at one of the lower doses, and some other patients with low performance status at entry did relatively badly. But after pausing, tightening up on the inclusion criteria, and adding extra patients to those cohorts, we were able to move through that.
75% Response Rate to New ALK Inhibitor
Editor's Note: The lung cancers sessions at the 2013 Annual Meeting of theAmerican Society of Clinical Oncology (ASCO®) were abuzz over data on a growing number of emerging targeted therapies. H. Jack West, MD, for Medscape, spoke to David Ross Camidge, MD, PhD, Associate Professor of Oncology at Colorado University, Denver, about data he presented on a highly promising ALK inhibitor, AP26113.
Medscape: Can you tell us a bit about the drug and the study that you are presenting today?
Dr. Camidge: AP26113 is a second-generation ALK and ROS1 inhibitor that seems in vitro to also have some activity against the activating epidermal growth factor receptor (EGFR) mutations and T790M. However, it needs to achieve an order of magnitude higher concentration to be active against the EGFR targets than it does against the ALK/ROS1 targets. We are showing the results from the phase 1 dose-escalation study across a broad dose range.
In the ALK patients, most of whom have not responded to crizotinib, we are seeing fantastic activity: a 75% response rate in patients who had progressed on crizotinib. That is occurring at doses from 60 mg all the way up to 240 mg. They are now taking 180 mg forward as the recommended phase 2 dose. It seems to be very well tolerated. One case of pneumonitis occurred at one of the lower doses, and some other patients with low performance status at entry did relatively badly. But after pausing, tightening up on the inclusion criteria, and adding extra patients to those cohorts, we were able to move through that.