CHICAGO―The selective CDK4/6 inhibitor LY2835219 is safe in patients diagnosed with solid tumors, according to results of a first-in-human phase 1 dose-escalation clinical trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
“LY2835219 shows acceptable safety and early clinical activity as a single agent for patients with advanced cancer,” concluded lead author Geoffrey Shapiro, MD, PhD, of the Dana-Farber Cancer Institute in Boston, MA, and coauthors.
Early clinical activity has been observed in patients with ovarian cancer, non-small cell lung cancer (NSCLC), breast cancer, and melanoma, the coauthors reported.
LY2835219 has shown antitumor activity and “distributes efficiently to the brain” in preclinical mouse studies, the authors noted. The authors performed the phase 1 trial to evaluate this agent’s safety and pharmacokinetics, and antitumor activity in 75 patients.
“3+3 dose escalation was followed by expansions in advanced cases of five tumor types (brain metastases permitted): NSCLC, glioblastoma, breast cancer, melanoma, and colorectal cancer,” they reported. “LY2835219 was taken orally every 12 or 24 hours (in escalation) and every 12 hours (in expansions) on days 1-28 of a 28-day cycle.”
The most frequent drug-related adverse events were diarrhea (52%; grade 3, 7%), nausea (30%; grade 3, 5%), fatigue (21%; grade 3, 5%), vomiting (21%; grade 3, 1%); and neutropenia (19%; grade 3, 7%), the coauthors reported.
“One patient with ovarian cancer had a durable CA-125 response with a greater than 50% decrease in 15 cycles,” the team reported. “One patient with KRAS mutant NSCLC had a 27% decrease by RECIST (Response Evaluation Criteria in Solid Tumors). One patient with CDKN2A -/- NRAS mutant melanoma had a confirmed partial response.”