Ceritinib Plus Nivolumab in NSCLC Characterized by an ALK Mutation

Among patients who were naive to ALK inhibition, the overall response rate was 83% for the 450-mg dose and 60% for the 300-mg dose.

The combination of ceritinib plus nivolumab seems to have activity in patients with ALK-rearranged non-small cell lung cancer (NSCLC), according to results of a phase 1b study.1 Response to the combination appeared to correlate with PD-L1 expression at baseline.

Currently, ceritinib — an oral ALK inhibitor — is approved for treatment of patients with metastatic ALK-rearranged NSCLC. Induction of PD-L1 expression due to constitutive oncogenic signaling has been reported in NSCLC models with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Therefore, this study was designed to test the combination of ceritinib with nivolumab, a PD-L1 inhibitor, in patients with stage IIIb/IV ALK-rearranged NSCLC who have received prior treatment or who are treatment-naive individuals.

In the study, 36 patients were treated with nivolumab 3 mg/kg every 2 weeks plus ceritinib at 450 mg (14 individuals) or 300 mg (22 individuals) daily.

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Among patients given the 450-mg dose, 4 had dose-limiting toxicities. In the 300-mg patient group, 2 had dose-limiting toxicities.

Among patients who were naive to ALK inhibition, the overall response rate was 83% for the 450-mg dose and 60% for the 300-mg dose. Among pretreated patients, overall response rate was 50% for the 450-mg dose and 25% for the 300-mg dose.

Response seemed to be greater in patients who were positive for PD-L1 expression at baseline compared with those who were negative for PD-L1 expression. With a cutoff of 1% or greater PD-L1 expression, response was 64%, compared with 31% in patients with negative staining.

Common grade 3/4 adverse events included increased alanine aminotransferase (25%), increased gamma-glutamyl transferase (22%), increase amylase (14%), increase lipase (11%) and maculopapular rash (11%).

According to the researchers, any survival results with this low of a sample size need to be interpreted with caution. In the 450-mg patient group, the median duration of response was 11.2 months, with estimated event-free rates at 6 months and 10 months of 80% in treatment-naïve patients and 75% in pretreated patients.

Median duration of response was not reached in the 300-mg group, due to a high proportion of responders. The estimated event-free rates at 10 months were 83% for treatment-naive patients and 67% for pretreated patients.

“Identifying subgroups of patients with ALK-rearranged NSCLC who may yet benefit from adding an anti-PD1 therapy to ceritinib remains a crucial challenge,” the researchers wrote. “Based on these safety findings, an alternative dosing regimen is being investigated in which ceritinib is administered as monotherapy for 2 cycles before initiation of the combination therapy with nivolumab.”


Felip E, de Braud FG, Maur M, et al. Ceritinib plus nivolumab in patients with advanced ALK-rearranged non-small-cell lung cancer: results of an open-label, multicenter, phase 1B study: ceritinib plus nivolumab in ALK-rearranged NSCLC [published online October 18, 2019]. J Thorac Oncol. doi: 10.1016/j.jtho.2019.10.006

This article originally appeared on Cancer Therapy Advisor