Avelumab as Single Agent in Metastatic or Locally Advanced Urothelial Cancer in Patients Unfit for Cisplatin. The ARIES Study

Summary

This is a single arm, open label, phase II study to evaluate the activity of avelumab (MSB0010718C) in patients with metastatic or locally advanced urothelial cancer considered unfit to cisplatin-based chemotherapy, to be conducted in conformance with Good Clinical Practices. Cisplatin-unfit patients will be defined if at least one of these characteristics is present: 1. ECOG-Performance status = 2; 2. Creatinine Clearance \< 60 ml/min; 3. Grade 2 or worse peripheral neuropathy or hearing loss; 4. Previous treatment with cisplatin for adjuvant intent in six months before the progression of disease.

Timeline

Start

2019-02-06

Primary completion

2021-09-15

Completion

2021-09-15

Publications

• Background Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996 May;8(5):765-72. doi: 10.1093/intimm/8.5.765.
• Background Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11(11):3887-95. doi: 10.1002/j.1460-2075.1992.tb05481.x.
• Background Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 2004 Feb 1;64(3):1140-5. doi: 10.1158/0008-5472.can-03-3259.
• Background Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002 Aug;8(8):793-800. doi: 10.1038/nm730. Epub 2002 Jun 24.

Drugs

Indications