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.

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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.”