A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, 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 NSCLC cohort and higher 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