A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

Noah M Hahn; Michael A O'Donnell; Jason A Efstathiou; Marianna Zahurak; Gary L Rosner; Jeff Smith; Max R Kates; Trinity J Bivalacqua; Phuoc T Tran; Daniel Y Song; Alex S Baras; Andres Matoso; Woonyoung Choi; Kellie N Smith; Drew M Pardoll; Luigi Marchionni; Bridget McGuire; Mary Grace Phelan; Burles A Johnson III; Tanya O'Neal; David J McConkey; Tracy L Rose; Marc Bjurlin; Emerson A Lim; Charles G Drake; James M McKiernan; Israel Deutsch; Christopher B Anderson; Donald L Lamm; Daniel M Geynisman; Elizabeth R Plimack; Mark A Hallman; Eric M Horwitz; Essel Al-Saleem; David Y T Chen; Richard E Greenberg; Alexander Kutikov; Gordon Guo; Timothy A Masterson; Nabil Adra; Hristos Z Kaimakliotis

doi:10.1016/j.eururo.2023.01.017

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A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

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A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

Noah M Hahn, Michael A O'Donnell, Jason A Efstathiou, Marianna Zahurak, Gary L Rosner, Jeff Smith, Max R Kates, Trinity J Bivalacqua, Phuoc T Tran, Daniel Y Song, …

European urology, Vol.83(6), pp.486-494

06/2023

DOI: 10.1016/j.eururo.2023.01.017

PMCID: PMC10192088

PMID: 36717286

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10192088/pdf/nihms-1870452.pdfView

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Abstract

Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). A multicenter phase 1 trial was conducted at community and academic sites. Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Bladder Cancer

Bacillus Calmette-Guerin

Durvalumab

Radiation

Bacillus Calmette-Guerin unresponsive

PD-L1

Clinical trial

Non–muscle invasive

Urothelial carcinoma

Details

Title: Subtitle: A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study
Creators: Noah M Hahn
Michael A O'Donnell - University of Iowa
Jason A Efstathiou
Marianna Zahurak - Johns Hopkins University
Gary L Rosner - Johns Hopkins University
Jeff Smith - Hoosier Cancer Research Network, Indianapolis, IN, USA
Max R Kates
Trinity J Bivalacqua
Phuoc T Tran
Daniel Y Song
Alex S Baras
Andres Matoso
Woonyoung Choi
Kellie N Smith
Drew M Pardoll
Luigi Marchionni
Bridget McGuire
Mary Grace Phelan
Burles A Johnson III
Tanya O'Neal - Johns Hopkins University
David J McConkey
Tracy L Rose
Marc Bjurlin
Emerson A Lim
Charles G Drake
James M McKiernan
Israel Deutsch
Christopher B Anderson
Donald L Lamm
Daniel M Geynisman - Fox Chase Cancer Center
Elizabeth R Plimack - Fox Chase Cancer Center
Mark A Hallman - Fox Chase Cancer Center
Eric M Horwitz - Fox Chase Cancer Center
Essel Al-Saleem - Fox Chase Cancer Center
David Y T Chen - Fox Chase Cancer Center
Richard E Greenberg - Fox Chase Cancer Center
Alexander Kutikov - Fox Chase Cancer Center
Gordon Guo
Timothy A Masterson - Indiana University
Nabil Adra - Indiana University
Hristos Z Kaimakliotis - Indiana University
Resource Type: Journal article
Publication Details: European urology, Vol.83(6), pp.486-494
DOI: 10.1016/j.eururo.2023.01.017
PMID: 36717286
PMCID: PMC10192088
NLM abbreviation: Eur Urol
ISSN: 0302-2838
eISSN: 1873-7560
Language: English
Electronic publication date: 01/28/2023
Date published: 06/2023
Academic Unit: Urology
Record Identifier: 9984363380202771

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