Logo image
Back
Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study
Journal article   Open access   Peer reviewed

Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study

Monika Joshi, Sheldon L. Holder, Junjia Zhu, Hong Zheng, Shraddha Komanduri, Joshua Warrick, Hesham Yasin, Rohan Garje, Bei Jia, Joseph J. Drabick, …
European urology focus, Vol.8(2), pp.483-490
03/01/2022
DOI: 10.1016/j.euf.2021.03.005
PMCID: PMC8812202
PMID: 33741296
url
https://doi.org/10.1016/j.euf.2021.03.005View
Published (Version of record) Open Access

Abstract

Patients with metastatic urothelial carcinoma (mUC) have poor prognosis, so further development of novel combinations for these patients is needed. To assess the safety and efficacy of eribulin mesylate (eribulin) with avelumab in mUC. This was an open-label, phase 1b study in which patients with mUC who were cisplatin-ineligible and treatment-naïve or platinum-resistant were treated with eribulin and avelumab. A 3 + 3 design was used. The study was prematurely terminated because the free study drug became unavailable, but we performed extended follow-up for patients enrolled in the study. Patients received eribulin 1.1 mg/m2 plus avelumab 10 mg/kg on days 1 and 15 in every 28-d cycle in cohort 0, or eribulin 1.4 mg/m2 plus avelumab 10 mg/kg on days 1 and 15 in every 28-d cycle in cohort +1. The primary objectives were to determine the maximum tolerated dose (MTD) of eribulin with avelumab and assess the objective response rate. A key secondary endpoint was to assess efficacy by evaluating the disease control rate. Exploratory endpoints included PD-1 expression on T cells in peripheral blood and in tumor cells, and tumor DNA sequencing. A total of six patients were enrolled in the MTD group (n = 3 in cohort 0 and n = 3 in cohort +1). No dose-limiting toxicity (DLT) was observed in cohort 0, whereas two DLT events were observed in cohort +1. Two patients in cohort 0 had a partial response that was durable, with one patient having a durable response for 7.8 mo. Disease control was observed in 4/6 patients (66.7%). Owing to the early termination, MTD could not be determined. While early termination of this trial precludes any definitive conclusions, the combination of eribulin and avelumab shows promise in mUC. We observed that treatment was better tolerated and efficacious at lower doses of eribulin. Further research is warranted for this combination in mUC. We evaluated different doses of eribulin (a chemotherapy drug) in combination with a fixed dose of avelumab (an antibody used to treat several different cancers) in a small group of patients with metastatic cancer of the urinary tract. The lower dose of eribulin was easier to tolerate and the combination had an anti-cancer effect. This trial is registered at ClinicalTrials.gov as NCT03502681. The combination of avelumab and low-dose eribulin showed encouraging safety and efficacy signals in a small cohort of patients with metastatic urothelial cancer. Responses were also observed among patients with FGFR abnormalities. This combination should be evaluated further in a larger clinical trial.
 Avelumab Eribulin Urothelial carcinoma

Details

Metrics

13 Record Views
6 Times Cited - Web of Science
Logo image