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Induction of PD-L1 expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring EML4-ALK rearrangements. We assessed safety and activity of ceritinib plus nivolumab in these patients. In this open-label, phase 1B, multicenter, dose-escalation and expansion study, previously treated (ALK inhibitor [ALKi]/chemotherapy) or treatment-naïve patients with stage IIIB/IV ALK-rearranged NSCLC received nivolumab 3 mg/kg intravenously every 2 weeks plus ceritinib (450 mg/300 mg) daily with low-fat meal. In total, 36 patients were treated (450 mg cohort [n=14]; 300 mg cohort [n=22]). In the 450 mg cohort, four patients experienced DLTs. In the 300 mg cohort, two patients experienced DLTs. Among ALKi-naïve patients, the overall response rate (ORR) was 83% (95% CI 35.9-99.6) in the 450 mg cohort and 60% (95% CI 26.2-87.8) in the 300 mg cohort. Among ALKi-pretreated patients, the ORR was 50% (95% CI 15.7-84.3) in the 450 mg cohort and 25% (5.5-57.2) in the 300 mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 as compared to those who were negative for PD-L1 with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% [95% CI 35.1-87.2] patients had confirmed responses as compared to those with negative PD-L1 staining (31% [95% CI 11.0-58.7]). Most frequently reported grade 3/4 adverse events were increased alanine aminotransferase (ALT) (25%), increased gamma-glutamyl transferase (22%), increased amylase (14%), increased lipase (11%), and maculopapular rash (11%). Incidence of all grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% patients in the 450 mg and 300 mg cohorts, respectively; no grade 4 rash was reported. Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent. |
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