A phase 3 trial designed to evaluate abemaciclib monotherapy for KRAS-mutated advanced non-small lung cancer failed to meet its primary endpoint of improved OS, according to the drug’s manufacturer.
“[Although] the outcome is unfortunate for patients with KRAS-mutated advanced lung cancer, we remain encouraged by the antitumor activity observed with abemaciclib (Verzenio, Eli Lilly) in this form of lung cancer where few clinical advances have been achieved,” Levi A. Garraway, MD, PhD, senior vice president of global development and medical affairs at Lilly Oncology, said in a company-issued press release.
The global, interventional, open-label phase 3 JUNIPER trial evaluated the efficacy and safety of abemaciclib — a cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor — compared with erlotinib (Tarceva; Genentech, Astellas) — an epidermal growth factor receptor inhibitor — for patients with stage IV NSCLC with a detectable KRAS mutation who progressed after platinum-based chemotherapy. Patients who received one additional systemic therapy were eligible.
The study included 453 patients. Researchers randomly them to 200 mg abemaciclib twice daily on a continuous dosing schedule or 150 mg erlotinib administered at its approved dose and schedule. Treatment continued until disease progression, death or unacceptable toxicity.
Although the study failed to meet its primary endpoint of OS, the trial met its secondary endpoints of improved PFS and overall response rates among abemaciclib-treated patients.
Researchers reported a higher OS rate in the control group than expected based on historical data in this setting, according to the press release.
The most common adverse events included diarrhea, fatigue, decreased appetite and nausea.
Full results from the trial will be submitted for presentation at a medical meeting next year.
“As we analyze secondary endpoints and explore specific patient subgroups in order to better evaluate the prospects for abemaciclib in NSCLC, we will continue to work with the oncology community to inform potential future treatment avenues for patients with KRAS-mutated advanced lung cancer,” Garraway said. “Moreover, we have several studies ongoing of rational combinations that include abemaciclib in non-small cell lung cancer and other malignancies. We look forward to seeing the results of these studies.”
As HemOnc Today previously reported, the FDA recently approved abemaciclib for the treatment of women with hormone receptor-positive, HER-2-negative advanced or metastatic breast cancer who progressed following endocrine therapy.