Hoosier Cancer Research Network (HCRN) has opened a study for patients with non-muscle invasive bladder cancer who were previously treated with the Bacillus Calmette-Guerin (BCG) vaccine. The randomized phase I/II clinical trial will test standard re-treatment with BCG against the immunotherapeutic agent durvalumab combined with BCG, or durvalumab combined with radiation therapy.

The study, known as ADAPT-BLADDER, or HCRN GU16-243, is currently open to accrual at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Md.; the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis, Ind.; and BCG Oncology, P.C., in Phoenix, Ariz., and will soon open at other HCRN sites in the United States.

BCG is one of the most common treatments for bladder cancer; yet, as the study’s sponsor-investigator Noah M. Hahn, MD, explains, many patients remain at risk of recurrence after treatment.

“Up to 50 percent of patients who achieve a complete eradication of their tumor with their first BCG exposure will develop recurrent tumors in follow-up,” Dr. Hahn, of Johns Hopkins Medicine, said. “We can treat those patients again, but only about 45 percent of patients who are re-treated with BCG achieve long-term tumor control.”

Durvalumab is a human monoclonal antibody directed against PD-L1 and belongs to a class of immunotherapy drugs known as checkpoint inhibitors. These drugs block an interaction between the body’s T cells and certain proteins commonly found on cancer cells that prevents the T cells from recognizing and attacking cancer cells as foreign. Durvalumab blocks PD-L1 interaction with PD-1 and CD80, countering the tumor’s immune-evading tactics and inducing an immune response. Studies involving checkpoint inhibitors in metastatic patients have shown activity in achieving durable responses for many patients. This study will help researchers learn what effect checkpoint inhibitors might have in early-stage bladder cancer.

The ADAPT-BLADDER study will be conducted in two phases.

In Phase I of this study, researchers will study durvalumab alone (Cohort 1) and then durvalumab combined with BCG (Cohort 2a) or radiation (Cohort 2b). Phase I will determine safety and recommended phase II dose from patients treated with durvalumab plus BCG or durvalumab plus radiation. Up to 42 patients will participate in Phase I.

Phase II will determine relapse-free survival (RFS), or how long a regimen is able to prevent the cancer from returning, for each experimental arm. Patients assigned to the BCG-only arm whose disease is determined to be BCG-unresponsive following a post-treatment disease re-evaluation and who continue to meet eligibility criteria for the study will have the opportunity to cross-over to durvalumab monotherapy. Up to 144 patients will participate in Phase II.

The use of durvalumab in this study is investigational. It has not been approved by the U.S. Food and Drug Administration to treat non-muscle invasive bladder cancer.

To be eligible for this study, patients must have non-muscle invasive bladder cancer and must have received prior BCG treatment. Other criteria must be met to enroll.

For more information about this study, visit: hoosiercancer.org/clinical-trials/trial/gu16-243/, or visit www.clinicaltrials.gov and search for study identifier NCT03317158.

Funding support for this trial is provided by AstraZeneca/MedImmune.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) 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 200 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,000 subjects have participated in Hoosier Cancer Research Network clinical trials.

About Durvalumab

Durvalumab is also being studied for first-line treatment as monotherapy and/or in combination with tremelimumab in the Phase III DANUBE trial in metastatic urothelial carcinoma. Durvalumab (Imfinzi^®) has already received accelerated approval in the U.S. for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.