Novartis announces data from ASCEND-3 Phase II study and ASCEND-5 Phase III study for Zykadia (ceritinib) to treat ALK+) non-small cell lung cancer.

Novartis announced updated results from a Phase II study (ASCEND-3), which demonstrated that anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) patients taking Zykadia (ceritinib) as their first ALK inhibitor (post-chemotherapy) had a median progression-free survival (PFS) of 18.4 months [95% CI: 10.9-26.3; median follow-up time of 25.9 months, as measured by blinded independent review committee (BIRC).Results were presented during an oral session at the Annual European Society for Medical Oncology Congress (ESMO) in Copenhagen. These results are consistent with findings from the Phase I ASCEND-1 study, which demonstrated a median PFS of 18.4 months (95% CI: 15.2-not reached) as per BIRC assessment with a median follow-up of 11.1 months. The previous analysis by BIRC in ASCEND-3 indicated that the median PFS had not been reached after a median follow-up time of 8.3 months. Further, in a sub-analysis of these data, patients who entered the study with brain metastases at baseline experienced an overall response rate (ORR) of 63.3% (95% CI: 48.3-76.6) and a disease control rate (DCR) of 83.7% (95% CI: 70.3-92.7), both as measured by BIRC. These results were similar to those in patients without brain metastases, who demonstrated an ORR of 64.0% (95% CI: 52.1-74.8) and DCR of 88.0% (95% CI: 78.4-94.4), based on BIRC assessment. At the time of analysis, the estimated 18-month overall survival (OS) rate was 73.4% (95% CI: 64.6-80.4). This population also demonstrated an ORR of 63.7% (95% CI: 54.6-72.2) and median duration of response of 23.9 months (95% CI: 16.6-not estimable), according to BIRC assessment. A decrease in tumor burden from baseline was shown in 94.7% patients (investigator assessment only, no BIRC assessment available).

Results from the randomized Phase III ASCEND-5 study were also presented for the first time, and were included as part of a late-breaking oral session as well as in the ESMO press program. The ASCEND-5 study assessed median PFS in patients previously treated with crizotinib (Xalkori) and one or two prior regimens of cytotoxic chemotherapy (including platinum doublet), who then received either Zykadia or standard chemotherapy. Results demonstrated a statistically significant and clinically meaningful improvement in median PFS by BIRC for patients taking Zykadia versus chemotherapy (HR 0.49, 95% CI 0.36-0.67; p<0.001 one sided). Median PFS by BIRC for Zykadia and chemotherapy were 5.4 months (95% CI: 4.1-6.9) vs. 1.6 months (95% CI: 1.4-2.8), respectively.

Comment:The ALK gene arrangement, one of the three most common biomarkers - or genetic drivers -of NSCLC, affects approximately 2-7% of cases each year. More than half of these patients are either former smokers or have never smoked. These patients are candidates for treatment with a targeted ALK inhibitor.