A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naive, cisplatin-ineligible urothelial cancer

Background: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). Patients and methods: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. Results: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (>median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (median) in the UC cohort. Treatment-related adverse events (TRAEs) occurred in 93.4% of patients, including grade >3 TRAEs in 55.7%. Avelumab exposures with 800 mg Q2W dosing were similar to those observed with 10 mg/kg Q2W dosing. Conclusions: In previously treated patients with advanced/metastatic NSCLC, ORR appeared to be superior to anti-PD-L1 or anti-programmed cell death protein 1 monotherapy, irrespective of PD-L1 status, whereas in untreated, cisplatin-ineligible patients with advanced/metastatic UC, ORR was lower than expected, potentially limited by small patient numbers. Trial registration: Clinicaltrial.gov NCT03472560; https://clinicaltrials.gov/ct2/show/NCT03472560

Automated summary

This study aimed to investigate the clinical outcomes of avelumab plus axitinib in advanced NSCLC or UC patients. The results showed that in NSCLC patients, objective response rate (ORR) was superior to anti-PD-L1 or anti-PD-1 monotherapy, regardless of PD-L1 status. In UC patients, ORR was lower than expected. Rating: 8 out of 10.