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

G Galffy; I Lugowska; E V Poddubskaya; B C Cho; M-J Ahn; J-Y Han; W-C Su; R J Hauke; S H Dyar; D H Lee; P Serwatowski; D L Estelles; V R Holden; Y J Kim; V Vladimirov; Z Horvath; A Ghose; A Goldman; A di Pietro; J Wang; D A Murphy; A Alhadab; M Laskov

doi:10.1016/j.esmoop.2023.101173

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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

Authors: G Galffy ; I Lugowska ; E V Poddubskaya ; B C Cho ; M-J Ahn ; J-Y Han ; W-C Su ; R J Hauke ; S H Dyar ; D H Lee ; P Serwatowski ; D L Estelles ; V R Holden ; Y J Kim ; V Vladimirov ; Z Horvath ; A Ghose ; A Goldman ; A di Pietro ; J Wang ; D A Murphy ; A Alhadab ; M Laskov

Citation: ESMO OPEN, Vol.8(3) : 101173, 2023-06

Journal Title: ESMO OPEN

Issue Date: 2023-06

MeSH: Antibodies, Monoclonal / adverse effects ; Axitinib / pharmacology ; Axitinib / therapeutic use ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / pathology ; Carcinoma, Transitional Cell* ; Cisplatin / pharmacology ; Cisplatin / therapeutic use ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / pathology ; Urinary Bladder Neoplasms*

Keywords: avelumab plus axitinib ; immune checkpoint inhibitor ; non-small-cell lung cancer ; urothelial carcinoma

Abstract: 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 (
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.