A Phase I Study of Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies
National Cancer Institute (NCI)
Summary
Background: Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug PDS01ADC triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. Objective: To learn if M7824 and PDS01ADC, with or without SBRT, can help the immune system to fight cancer better. Eligibility: People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body. Design: Participants will be screened with: medical history physical exam ability to do their normal activities blood tests urine tests electrocardiogram body scans. Participants will give a tumor sample or have a tumor biopsy. Screening tests will be repeated during the study. Participants will get PDS01ADC . It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT. Participants will give tissue and saliva samples. Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely.
Description
Background: * Urothelial carcinoma (UC), renal cell carcinoma (RCC) and other non-prostate genitourinary cancers are lethal in the metastatic state. * Immune checkpoint inhibitors targeting the Programmed Cell Death Protein 1 (PD-1)/ Programmed Death-Ligand 1 (PD-L1) pathway have greatly changed clinical management of metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC). * Several PD-1/PD-L1 inhibitors are Food and Drug Administration (FDA)-approved for non-prostate genitourinary cancers including five agents for second-line mUC, two agents for first-line cisplatin…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Participants must have histologically or cytologically confirmed diagnosis of a metastatic non-prostate genitourinary tumor. * Participants must have metastatic disease defined as new or progressive lesions on cross-sectional imaging. Radiological evaluation should occur within 21 days prior to enrollment. * Participants must have evaluable or measurable disease, per RECIST 1.1. * Participants in Arms 2 and 3 must have at least one site of disease that is amenable to irradiation (irradiation of up to 4 different sites is permitted) * Participants must have at least one…
Interventions
- RadiationStereotactic body radiation therapy (SBRT)
A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and PDS01ADC
- DrugPDS01ADC
An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT
- DrugM7824
1200 mg administered IV every two weeks while on PDS01ADC and with or without SBRT
Location
- National Institutes of Health Clinical CenterBethesda, Maryland