Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study.
Avelumab
Eribulin
Urothelial carcinoma
Journal
European urology focus
ISSN: 2405-4569
Titre abrégé: Eur Urol Focus
Pays: Netherlands
ID NLM: 101665661
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
15
12
2020
revised:
04
02
2021
accepted:
01
03
2021
pubmed:
21
3
2021
medline:
9
6
2022
entrez:
20
3
2021
Statut:
ppublish
Résumé
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/m 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.
Sections du résumé
BACKGROUND
Patients with metastatic urothelial carcinoma (mUC) have poor prognosis, so further development of novel combinations for these patients is needed.
OBJECTIVE
To assess the safety and efficacy of eribulin mesylate (eribulin) with avelumab in mUC.
DESIGN, SETTING, AND PARTICIPANTS
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.
INTERVENTION
Patients received eribulin 1.1 mg/m
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
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.
RESULTS AND LIMITATIONS
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.
CONCLUSIONS
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.
PATIENT SUMMARY
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.
Identifiants
pubmed: 33741296
pii: S2405-4569(21)00062-6
doi: 10.1016/j.euf.2021.03.005
pmc: PMC8812202
mid: NIHMS1768651
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Furans
0
Ketones
0
avelumab
KXG2PJ551I
eribulin
LR24G6354G
Banques de données
ClinicalTrials.gov
['NCT03502681']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
483-490Subventions
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Informations de copyright
Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.