An overall response rate (ORR) of 72.7% was observed in an interim analysis of a phase 1 study evaluating the combination of sintilimab, an inhibitor of the programmed cell death-1 (PD-1) receptor, and anlotinib, a tyrosine kinase inhibitor (TKI), for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The findings from this study were presented at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.

In 2018, the US Food and Drug Administration (FDA) approved the combination of an antiangiogenic agent, bevacizumab; a programmed cell death-ligand 1 inhibitor (PD-L1), atezolizumab; and carboplatin-paclitaxel chemotherapy as a first-line option for patients with advanced non-squamous NSCLC that is not characterized by genomic alterations in EGFR or ALK

In this phase 1 study ( Identifier: NCT03628521), a chemotherapy-free regimen of the combination of sintilimab and anlotinib was investigated. Researchers also looked at the combinations of anlotinib plus chemotherapy, as well as anlotinib plus erlotinib.

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All patients enrolled in the phase 1 study were adults who were naive to systemic therapy for NSCLC, and had EGFR and ALK wild-type disease. Only results for those patients enrolled in the sintilimab-anlotinib combination arm (ie, intravenous sintilimab [200 mg every 3 weeks] and oral anlotinib [12 mg/day; 2 weeks on and 1 week off]) were reported during the WCLC meeting, although there are 3 different study arms in this nonrandomized, open-label trial. Primary outcome measures were safety and ORR.

Of the 22 patients enrolled in the sintilimab plus anlotinib arm, almost all were men with stage III/IV NSCLC, with approximately two-thirds identified as former/current smokers, and slightly over half with disease characterized by squamous histology. Baseline assessments of the tumor level of programmed cell death-ligand 1 (PD-L1) revealed a “high” status in 13 of the 21 patients who underwent testing. In addition, tumor mutational burden (TMB) was determined to be high in 7 of the 18 patients tested.

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In addition to the very high ORR (all partial responses), patients receiving the combination of sintilimab and anlotinib had a disease-control rate (DCR) of 100%, and a 6-month progression-free survival (PFS) rate of 93.8%.

Interestingly, while the ORRs were similar in the subgroups of patients with tumors characterized by high and low PD-L1 expression levels, in the patient subgroups with high and low TMB, the ORR was 85.7% and 63.6%, respectively.

Regarding safety, the combination of sintilimab and anlotinib was considered to be well tolerated, with grade 3 or higher treatment-related adverse events observed in 27.3% of patients. Among all treatment-related adverse events, fecal occult blood, hyperuricemia, hyponatremia, and hand-foot syndrome were the most common.

In their concluding remarks, the study authors noted that the chemotherapy-free combination of sintilimab and anlotinib was “worthy of further development” as a first-line treatment in advanced NSCLC.


Han B, Chu T, Zhong R, et al. Efficacy and safety of sintilimab with anlotinib as first-line therapy for advanced non-small cell lung cancer (NSCLC). Presented at:  IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract JCSE01.11.

This article originally appeared on Cancer Therapy Advisor