Renal Medullary Carcinoma

Background:
Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU.
Objective:
To test SG, either alone or combined with atezolizumab, in people with rare GU tumors.
Eligibility:
Adults aged 18 years and older with rare GU tumors. These may include small cell carcinoma of the bladder; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor.
Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm.
All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle.
Blood and urine tests, imaging scans, and other exams will be repeated during study visits.
Treatment may continue for up to 5 years.
Follow-up visits will continue for 5 more years.

This is a single-arm, monocentric, phase II trial, enrolling patients with histological diagnosis of collecting duct carcinoma and renal medullary carcinoma with locally advanced or metastatic disease who will be treated with Pembrolizumab plus Enfortumab Vedotin.
Approximately, 23 patients will be enrolled. At screening, pre-existing archival primary and metastatic FFPE tumor specimen will be collected and submitted for central pathology review and translational analysis. All participants will undergo baseline screening imaging for clinical staging. Patients will be treated with Pembrolizumab q21 plus Enfortumab Vedotin 1,8q21 for 3 cycles (3 infusion of Pembrolizumab and 6 infusion of Enfortumab Vedotin) then radiological imaging will be repeated and patients with SD, PR or CR will continue pembrolizumab until disease progression, unacceptable toxicities or completion of treatment (17 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice.
Patients who will experience progressive disease during pembrolizumab monotherapy treatment could restart Enfortumab Vedotin.
The study will also involve collection of a blood sample taken at the commencement of treatment, at the first cycle, after cycle 3 and at the end of treatment or progression of disease, to be used for research purposes.

To learn if the combination of nivolumab and relatlimab can help to control renal medullary carcinoma (RMC) that is locally advanced or metastatic (has spread).