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Clinical Trial
. 2021 Feb;10(3):1074-1083.
doi: 10.1002/cam4.3699. Epub 2020 Dec 31.

A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract

Michal Sarfaty  1   2 , Karissa Whiting  3 , Min Yuen Teo  1   4 , Chung-Han Lee  1   4 , Vanessa Peters  1 , Jennifer Durocher  1 , Ashley M Regazzi  1 , Asia S McCoy  1 , Grace Hettich  1 , Achim A Jungbluth  5 , Hikmat Al-Ahmadie  5 , Irina Ostrovnaya  3 , Joshua Chaim  6 , Dean F Bajorin  1   4 , Jonathan E Rosenberg  1   4 , Gopa Iyer  1   4 , Samuel A Funt  1   4
Affiliations
Clinical Trial

A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract

Michal Sarfaty et al. Cancer Med. 2021 Feb.

Abstract

Background: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited.

Methods: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0-1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing.

Results: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median follow-up of 7.38 months (range, 5.23-21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3-4 treatment-related adverse events occurred in 38.4% of patients.

Conclusions: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.

Keywords: adenocarcinoma; immunotherapy; small cell carcinoma; squamous cell carcinoma; urothelial carcinoma; variant histology.

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Conflict of interest statement

Michal Sarfaty reports consulting fees from Merck, Novartis, and Roche. Chung‐Han Lee reports institutional research funds from Bristol‐Myers Squib, Calithera, Eisai, Eli Lilly, Exelixis, and Merck, Pfizer and consulting for Amgen, Bristol‐Myers Squib, Exelixis, Eisai, Merck, Pfizer, and EMD Serono. Dean F. Bajorin reports consulting fees from Bristol Myers Squibb, Merck, Genentech‐Roche, AstraZeneca, and Pfizer and institutional research support from Merck, Genentech‐Roche, AstraZeneca, Novartis, and Bristol‐Myers Squibb. Jonathan E. Rosenberg reports consulting fees from AstraZeneca, Bristol‐Myers Squibb, Merck, Roche, Genentech, Seattle Genetics, Astellas, Boehringer Ingelheim, Janssen, Pfizer, EMD Serono, GSK, and Mirati, and institutional research funding from Bayer, Astra Zeneca, and Seattle. Gopa Iyer reports consulting or advisory role for Bayer, Janssen, and Mirati Therapeutics; and has received research funding from Mirati Therapeutics, Novartis, Debiopharm Group, and Bayer. Hikmat Al‐Ahmadie reports consulting or advisory role for Bristol Myers Squibb, EMD Serono, AstraZeneca/MedImmune, and Janssen Biotech. Samuel A. Funt reports consulting fees from Merck; institutional research support from AstraZeneca and Genentech/Roche; stock and other ownership interest in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, Iconovir, and Vida Ventures. The other authors made no disclosures.

Figures

FIGURE 1
FIGURE 1
Swimmer's Plot. *Patient 12 completed 56 weeks of treatment on protocol and continues commercial use of durvalumab. * PD‐L1 status unknown for patients 2 and 6
FIGURE 2
FIGURE 2
Progression‐free survival and overall survival
FIGURE 3
FIGURE 3
Oncoprint
See this image and copyright information in PMC

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