WEEKLY IMPORTANT NEWS FROM MEDSCAPE AND OTHER SOURCES
Κυριακή, 18 Δεκεμβρίου 2016
ANTI-DLLL3 TREATMENT FOR SCLC
In a phase I study reported in The Lancet Oncology, Rudin et al found that rovalpituzumab tesirine, a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), produced responses in patients with recurrent small cell lung cancer (SCLC). DLL3 is a target identified in tumor-initiating cells that has been found to be expressed in > 80% of patients with SCLC.
Study Details and Toxicity
The study included 74 patients with SCLC previously treated with one or two chemotherapy regimens, including a platinum-based regimen. Dose-escalation or -expansion cohorts received doses of 0.05 mg/kg to 0.8 mg/kg given intravenously every 3 or 6 weeks, followed by investigation of 0.3 and 0.4 mg/kg every 6 weeks and 0.2 mg/kg every 3 weeks.
Dose-limiting toxicity was observed at 0.8 mg/kg every 3 weeks, including grade 4 thrombocytopenia in 2 patients and grade 4 liver function test abnormalities in 1 patient. The most common grade ≥ 3 treatment-related adverse events were thrombocytopenia (11%), pleural effusion (8%), and increased lipase (7%). Drug-related serious adverse events occurred in 38%. The maximum tolerated dose was 0.4 mg/kg every 3 weeks, with the dose of 0.3 mg/kg every 6 weeks moving forward into phase II study.
At active doses, consisting of 0.2 or 0.4 mg/kg every 3 weeks or 0.3 or 0.4 mg/kg every 6 weeks, objective response was observed in 11 of 60 assessable patients (18%), including in 10 of 26 (38%) with confirmed high DLL3 expression.
The investigators concluded: “Rovalpituzumab tesirine shows encouraging single-agent antitumour activity with a manageable safety profile. Further development of rovalpituzumab tesirine in DLL3-expressing malignant diseases is warranted.”