Researchers participating in the study known as ADAPT-BLADDER, or HCRN GU16-243, recently reported preliminary findings in the journal European Urology. The study evaluated the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (cohort 1), durvalumab plus Bacillus Calmette-Guerin (BCG) (cohort 2) and durvalumab plus external beam radiation therapy (EBRT) (cohort 3).

Led by sponsor-investigator Noah M. Hahn, MD of Johns Hopkins Medicine, this study is for patients with non-muscle invasive bladder cancer who were previously treated with the Bacillus Calmette-Guerin (BCG) vaccine. Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients.

The randomized phase I/II clinical trial tested standard re-treatment with BCG against the immunotherapeutic agent durvalumab combined with BCG, or durvalumab combined with radiation therapy. The recommended phase 2 dose for each regiment was the primary endpoint. Secondary endpoints included toxicity profiles and complete response rates.

A total of twenty-eight patients were treated in three cohorts. Full dose durvalumab, full-dose BCG and 6 Gy fractions x 3 were determined as the recommended phase 2 dose.

One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-month complete response occurred in 64% of all patients and in 33%, 85%, and 50% within the durvalumab, durvalumab + BCG, and durvalumab + EBRT cohorts, respectively. Twelve-month complete response was achieved in 46% of all patients and in 73% of durvalumab + BCG and 33% of durvalumab + EBRT patients.

Durvalumab combined with intravesical BCG or EBRT was proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging the 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.

This multi-arm multi-stage phase 1/2 study was conducted at community and academic sites including BCG Oncology, P.C., Columbia University Irving Medical Center, Dana Farber Cancer Institute, Fox Chase Cancer Center, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Rush University Medical Center, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Sitemen Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, University of Iowa Holden Comprehensive Cancer Center, University of North Carolina Lineberger Comprehensive Cancer Center.

Study authors include Noah M. Hahn, Michael A. O’Donnell, Jason A. Efstathiou, Jeff Smith, Marianna Zahurak, Gary L. Rosner, 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

View the abstract: https://www.europeanurology.com/article/S0302-2838(23)00025-8/fulltext#%20  

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 230 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 9,000 subjects have participated in Hoosier Cancer Research Network clinical trials.