P1.18-04 Neoadjuvant Ceritinib for Locally Advanced Non-Small Cell Lung Cancer with ALK Rearrangement: SAKULA Trial

Ceritinib is a highly selective ALK inhibitor that has been shown potent antitumor activity against ALK-positive non-small cell lung cancer (NSCLC). We conducted a multicenter single-arm phase II study to assess the efficacy and safety of neoadjuvant therapy with ceritinib followed by surgery in patients with ALK-positive resectable locally advanced (LA) NSCLC. Three cycles of ceritinib were administered as induction therapy. The drug was administered orally at the dose 750 mg once daily for 28 days per cycle. The primary endpoint was the major pathological response rate (mpRR). This study required 19 patients, with mpRR of 15% considered non-promising and 45% promising (one-side alpha = 0.025; beta = 0.2). Biomarker analyses using pre- and post-ceritinib through next-generation sequencing (NGS) of plasma and tissue is also planned. (Trial Identifier, UMIN000017906). A total of 395 patients with LA-NSCLC were screened from March 2015 to March 2018 and 15 patients (4%) were identified as ALK-positive. Only 7 patients were enrolled because of slow accrual. The median age of the patients was 50 years and 71% (n=5) were male. All patients had stage IIIA disease and adenocarcinoma. 6 out of 7 patients completed three cycles of neoadjuvant therapy with ceritinib as planned, 71% (n=5) of patients required dose adjustment. One patient was withdrawn from the study because of hepatitis. The objective clinical response rate was 100%. Surgical resection was performed in 6 patients, and complete (R0) resection was achieved in 5 patients. Among the 7 evaluable patients, the mpRR was 57% (95% CI, 18 to 90); 4 patients achieved mpR and 2 patients achieved pathologic complete response. With a median follow-up of 10 (range 8-33) months, 1 patient died of disease progression and 6 patients remain alive, including 4 patients who are recurrence-free. The most common toxicities were gastrointestinal toxicities. Our results showed that neoadjuvant ceritinib is safe and effective, with a high rate of pathologic response, in patients with ALK-positive resectable LA-NSCLC, although the limitation of the data interpretation due to small sample size.