The overall response rate was 42% in cohort 1 and 52% in cohort 2, Dr. Vij reported. The median time to disease progression was 8.3 months and median duration of response was 13.1 months in cohort 1. Neither end point had been reached in cohort 2.
Dr. Vij noted that the higher response rates in cohort 2 do not appear to be associated with higher side effects. Mild to moderate peripheral neuropathy was reported in 14% of cohort 1 and 19% of cohort 2. Only one case of grade-3 peripheral neuropathy was reported in cohort 1 and none in cohort 2.
The most common adverse events in cohort 1 and cohort 2, respectively, were fatigue (71%, 54%), nausea (54%, 44%), anemia (46%, 39%), dyspnea (49%, 30%), cough (39%, 30%) and pyrexia (36%, 33%). The majority were grade 1/2; adverse events leading to carfilzomib discontinuation occurred in 22% of cohort 1 and 10% of cohort 2, he said.
These data are suggestive of a dose-response relationship and are being further evaluated in the exploratory phase 1b/2 study PX-171-007, Dr. Vij said.
The trials were sponsored by Onyx Pharmaceuticals. Dr. Jakubowiak and his coauthors and Dr. Vij and his coauthors reported financial relationships with several pharmaceutical firms, including Onyx.