Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9

Abstract

Clinical experience of ceritinib in patients who progressed on alectinib is limited. In this prospective phase II study, we evaluated the activity of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC) in Japan. All patients were required to have ≥1 measurable lesion per RECIST, 1.1, and a World Health Organization Performance Status (WHO PS) of 0-1. Prior crizotinib and/or up to 1 chemotherapy regimen was allowed. Primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1. Ceritinib was given at a dose of 750 mg/day fasted. A total of 20 patients were enrolled from August 2015 to March 2017. All patients received prior alectinib (100%), 13 (65.0%) patients received prior platinum-based chemotherapy, and 4 (20%) patients received prior crizotinib. Median duration of exposure and the follow-up time with ceritinib were 3.7 months (range: 0.4-15.1) and 11.6 months (range: 4.8-23.0), respectively. Investigator-assessed ORR was 25% (95% CI: 8.7-49.1). Key secondary endpoints, all investigator assessed, included disease control rate (70.0%; 95% CI: 45.7-88.1), time to response (median, 1.8 months; range: 1.8-2.0), and duration of response (median, 6.3 months; 95% CI: 3.5-9.2). Median progression-free survival was 3.7 months (95% CI: 1.9-5.3). The most common adverse events reported were diarrhea (85.0%), nausea (80.0%), and vomiting (65.0%). Based on our findings, ceritinib could be considered as one of the treatment options for patients with ALK-positive NSCLC who progressed on alectinib. (Trial registration no. NCT02450903).

Keywords: ALK; Japan; NSCLC; anaplastic lymphoma kinase; ceritinib.

Figure 1

A, Waterfall plot of best percentage change from baseline by investigator review (includes 17 patients with measurable disease at baseline and at least 1 valid post‐baseline assessment). n is the number of patients with measurable disease at baseline and at least 1 valid post‐baseline assessment. * % change in target lesion available but contradicted by overall lesion response = progressive disease (contradicting assessment represents the only valid post‐baseline assessment). ALK mutations are reported for 5 patients; rest of the 12 patients did not have ALK mutations reported. B, Individual swimmer plots for all patients receiving ceritinib treatment. Only tumor responses assessed before start of new antineoplastic therapy are presented. ALK mutation in ctDNA at cycle 1 d 1 (C1D1) or end of treatment (EOT). Patient 5: L1196M (C1D1 and EOT), Patients 6 and 8: G1202R (EOT), Patient 10: G1202 (C1D1), Patient 13: G1269A (C1D1), Patient 14: G1202R (C1D1 and EOT), and Patient 19: G1202R, V1180L, and I1171N (C1D1). C, PFS by investigator assessment in patients with ALK‐rearranged NSCLC. n is the number of PFS events among patients included in the analysis (N). ALK, anaplastic lymphoma kinase; CI, confidence interval; CR, complete response; ctDNA, circulating tumor DNA; NSCLC, non‐small‐cell lung cancer; PD, progressive disease; PFS, progression‐free survival; PR, partial response