Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial

Nir Kleinmann, Surena F. Matin, Phillip M. Pierorazio, John L. Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott Hubosky, Marcelino Rivera, Michael O'Donnell, Marcus Quek, Jay D. Raman, John J. Knoedler, Douglas Scherr, Joshua Stern, Christopher Weight, Alon Weizer, Michael Woods, Hristos KaimakliotisAngela B. Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R. Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Mehrad Adibi, Mahul B. Amin, Elyse Seltzer, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Mark Schoenberg, Seth P. Lerner

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BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.

METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with, NCT02793128.

FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.

INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.

FUNDING: UroGen Pharma.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalThe Lancet Oncology
Issue number6
StatePublished - Jun 2020

Bibliographical note

Funding Information:
This trial was supported with funding from UroGen Pharma (New York, NY, USA). The study team thanks the patients and their families and caregivers for volunteering to participate in this trial. We also wish to thank Kim Thacker of UroGen Pharma for technical support, and Mary Susan Prescott of Prescott Medical Communications Group (Chicago, IL, USA) for editorial assistance with financial support from UroGen Pharma.

Publisher Copyright:
© 2020 Elsevier Ltd


  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic/administration & dosage
  • Carcinoma/drug therapy
  • Drug Carriers
  • Drug Compounding
  • Female
  • Humans
  • Hydrogels
  • Israel
  • Kidney Neoplasms/drug therapy
  • Male
  • Middle Aged
  • Mitomycin/administration & dosage
  • Neoplasm Grading
  • Time Factors
  • Treatment Outcome
  • United States
  • Urothelium/drug effects

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Multicenter Study
  • Clinical Trial, Phase III
  • Journal Article


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