Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non-small-cell lung cancer

Purpose To evaluate the efficacy of the pan-ERBB inhibitor, CI- 1033, in platinum- refractory or recurrent advanced-stage non-small-cell lung cancer ( NSCLC). Patients and Methods This open-label, randomized phase II trial evaluated CI- 1033 in patients with advanced- stage NSCLC who experienced treatment failure after or were refractory to platinum- based chemotherapy. Three oral CI- 1033 doses were evaluated in 21- day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1- year survival rate. Results One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug- related adverse events were rash and diarrhea. The 450- mg arm ( 14 days on/ 7 days off) was closed early due to an excessive rate of adverse events. The 1- year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression. Conclusion CI- 1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.