Indiana University Melvin and Bren Simon Cancer Center is leading a phase II clinical trial that will test the PD-L1 checkpoint inhibitor atezolizumab plus chemotherapy in patients with advanced urothelial cancer who are cisplatin-ineligible and whose cancer worsened after treatment with a PD-1 or PD-L1 inhibitor.

The study, HCRN-GU17-295, is open to accrual at the IU Simon Cancer Center in Indianapolis and Methodist Hospital in Omaha, Neb.

Urothelial cancer is a type of cancer that originates in urothelial cells that line the urinary system, including the urethra, bladder, ureters, and renal pelvis. It is the most common form of bladder cancer. Approximately 55,000 men and 17,000 women are diagnosed with bladder cancer annually.

The standard approach to treating metastatic urothelial cancer is cisplatin-based chemotherapy, which some patients are not able to tolerate because of poor health or organ function. Treatment for patients who cannot tolerate cisplatin include chemotherapies such as carboplatin, gemcitabine, docetaxel, or pemetrexed.

“Even though carboplatin and gemcitabine can be effective in this patient population, unfortunately these responses are usually short-lived, and they offer minimal benefit to these patients, and hence we are performing this clinical trial to try and improve this,” said Nabil Adra, MD, sponsor-investigator of the study and a medical oncologist at the IU Simon Cancer Center.

Dr. Adra said the main purpose of the study is to determine whether the combination of immunotherapy plus standard chemotherapy might offer a clinical benefit compared to standard chemotherapy alone, after patients progress on PD-1 or PD-L1 therapy.

“If we continue immunotherapy after patients progress on those treatments,” Dr. Adra continued, “we could potentially either sensitize or resensitize these bladder cancers to the effects of immunotherapy drugs. A lot of those patients either had short benefits or no benefit at all from immunotherapy and our hope is that the chemotherapy will not only attack the cancer, but it will also serve as an immunomodulatory effect by activating the immune system and help immunotherapy work better in this setting.”

Researchers hope to determine whether adding atezolizumab to chemotherapy will shrink cancer or delay disease progression for a longer period and determine whether this approach is more effective than the standard treatment.

Up to 37 subjects will be enrolled in the study, where atezolizumab and chemotherapy including carboplatin plus gemcitabine or docetaxel will be administered through an intravenous infusion through a vein.

Carboplatin is a platinum-based chemotherapy drug and is used to treat several cancers, including lung, ovarian, and head and neck cancers. Gemcitabine is a chemotherapy drug which is used to treat a variety of cancers, including bladder, breast, lung, ovarian, and pancreatic cancers. Docetaxel is another chemotherapy drug which is used to treat several cancers, including breast cancer, lung cancer, prostate cancer, head and neck cancer, and gastric or gastroesophageal junction cancer.

Atezolizumab is a type of drug called a PD-L1 immune checkpoint inhibitor, which binds to a protein found on some cancer cells, called programmed death-ligand 1 (PD-L1). By binding to PD-L1, atezolizumab helps the body’s immune system to recognize and fight cancer cells.

Atezolizumab is approved by the U.S. Food and Drug Administration (FDA) to treat certain types of advanced or metastatic urothelial cancer, cisplatin-ineligible bladder cancer, metastatic non-small cell lung cancer, extensive-stage small cell lung cancer, and triple-negative breast cancer. Learn more about atezolizumab (also known as TECENTRIQ®) at tecentriq.com.

Combining atezolizumab with chemotherapy in metastatic urothelial cancer after disease progression on single-agent PD-1 or PD-L1 therapy has not been FDA approved and should be considered investigational.

“We hope that with the addition of chemotherapy to immunotherapy, we are able to better activate the immune system to fight the cancer, and therefore we would get better effects from the immunotherapy drug rather than having it as a single agent,” Dr. Adra said.

Participants will receive treatment in 21-day cycles. Those who received prior platinum therapy for metastatic disease will receive atezolizumab with docetaxel. Those who did not receive prior platinum therapy will receive atezolizumab with carboplatin and gemcitabine. Participants may discontinue treatment at any time in consultation with their doctor.

In addition, blood and tissue will be collected to support correlative research for the study.

To qualify for the study, patients must be adults age 18 or older, who are cisplatin-ineligible and whose cancer is growing after treatment with a PD-1 or PD-L1 inhibitor.

The study is supported by Genentech.

For more information, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03737123).

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 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.