Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small-Cell Lung Cancer.

INTRODUCTION: This Phase II study evaluated the efficacy and safety of the pan-cyclin-dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease small-cell lung cancer.

METHODS: In this randomized, double-blind study, unselected patients with previously untreated ED-SCLC received roniciclib 5 mg or placebo twice daily in a 3 days on/4 day off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1, and etoposide on days 1-3. The primary endpoint was progression-free survival. Other endpoints included overall survival (OS), objective response rate (ORR), and safety.

RESULTS: 140 patients received treatment: 70 with roniciclib + chemo and 70 with placebo + chemo. Median PFS was 4.9 months (95% confidence interval [CI]: 4.2-5.5) with roniciclib + chemo and 5.5 months (95% CI: 4.6-5.6) with placebo + chemo (hazard ratio [HR] = 1.242; 95% CI: 0.820-1.881; p = 0.8653). Median OS was 9.7 months (95% CI: 7.9-11.1) with roniciclib + chemo and 10.3 months (95% CI: 8.7-11.9) with placebo + chemo (HR = 1.281; 95% CI: 0.776-1.912; p = 0.7858). The objective response rate was 60.6% with roniciclib + chemo and 74.6% with placebo + chemo. Common treatment-emergent adverse events (TEAEs) in both groups included nausea, vomiting, and fatigue. Serious TEAEs were more common with roniciclib + chemo (57.1%) than placebo + chemo (38.6%).

CONCLUSIONS: Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with ED-SCLC and the study was prematurely terminated.