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

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

ESMO Open. 2023 Jun;8(3):101173. doi: 10.1016/j.esmoop.2023.101173. Epub 2023 May 2.

Authors

G Galffy¹, I Lugowska², E V Poddubskaya³, B C Cho⁴, M-J Ahn⁵, J-Y Han⁶, W-C Su⁷, R J Hauke⁸, S H Dyar⁹, D H Lee¹⁰, P Serwatowski¹¹, D L Estelles¹², V R Holden¹³, Y J Kim¹⁴, V Vladimirov¹⁵, Z Horvath¹⁶, A Ghose¹⁷, A Goldman¹⁸, A di Pietro¹⁹, J Wang²⁰, D A Murphy²¹, A Alhadab²¹, M Laskov²²

Affiliations

¹ Department of Pulmonology, Pulmonology Hospital Törökbálint, Törökbálint, Hungary. Electronic address: galffy.gabriella@torokbalintkorhaz.hu.
² Early Phase Clinical Trials Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
³ Vitamed LLC, Moscow, Russia.
⁴ Division of Medical Oncology, Yonsei Cancer Center, Severance Hospital, Seoul.
⁵ Department of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
⁶ Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
⁷ Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
⁸ Department of Oncology, Nebraska Cancer Specialists, Omaha.
⁹ Department of Hematology & Oncology, Saint Francis Hospital Cancer Center, Greenville, USA.
¹⁰ Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
¹¹ Centrum Medyczne Dom Lekarski SA, Szczecin, Poland.
¹² Department of Oncology, Consorcio Hospitalario Provincial de Castellon, Castellon, Spain.
¹³ Oncology Hematology Associates, Springfield, USA.
¹⁴ Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.
¹⁵ GBUZ of Stavropol Territory Pyatigorsk Inter-regional Oncology Dispensary, Pyatigorsk, Stavropol Territory, Russia.
¹⁶ Bács-Kiskun Megyei Kórház Onkoradiológiai Központ, Kecskemet, Hungary.
¹⁷ Department of Medical Oncology/Hematology, Arizona Oncology Associates, Tempe.
¹⁸ Pfizer, Collegeville, USA.
¹⁹ Pfizer Italia Srl, Rome, Italy.
²⁰ Pfizer, Cambridge.
²¹ Pfizer, San Diego, USA.
²² LLC University Clinic of Headache, Moscow, Russia.

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 (<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.

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

Publication types

Clinical Trial, Phase II

MeSH terms

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*

Substances

avelumab
Axitinib
Cisplatin
Antibodies, Monoclonal

Associated data

ClinicalTrials.gov/NCT03472560