Background:
Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers.
Objective:
To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract.
Eligibility:
People aged 18 and older with rarer cancers of the testicles or urinary tract.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. Their ability to perform normal daily activities will be tested. They will have exams of their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue will be removed from the tumor.
The study drugs are both given through a tube attached to a needle inserted into a vein in the arm. Some participants will receive treatments 3 times during 28-week cycles; others will receive treatments 2 times during 21-day cycles.
All participants may continue to receive treatments for up to 5 years. Imaging scans and other tests will be repeated.
Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until the disease gets worse. They will have imaging scans and blood tests.
After that, follow-up visits will continue by phone every 3 months for up to 5 years after study therapy is finished.
Participants must have histologically confirmed locally advanced or metastatic pure adenocarcinoma of the urinary tract, pure squamous cell carcinoma of the urinary tract, or treatment-refractory testicular germ cell tumors. Note: For the purposes of enrollment, the urinary tract is defined as the renal pelvis, ureter, bladder, and urethra.
Participants must have measurable disease, per RECIST 1.1.
Participants must have locally advanced or metastatic disease defined as new or progressive lesions on cross sectional imaging.
Participants in Cohorts A1, B1, and C1 must have received prior anti-PD-1/PD-L1 therapy in any setting.
Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 2 weeks prior to the first study drug administration. Note: FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) are allowed to be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the investigator prior to enrollment.
Participants with prior treatment with EV or other MMAE-based ADCs.
Participants with preexisting sensory or motor neuropathy Grade >= 2.
History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to EV and/or pembrolizumab.
Parallel
Pembrolizumab
DrugPembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle.
Enfortumab vedotin
DrugEV is administered IV at 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle (Arm 1) and on days 1 and 8 of each 21-day cycle (Arm 2).
Objective response rate (ORR)
Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy
Second Objective response rate (ORR2) and second progression-free survival (PFS2) after second course of pembrolizumab
Percentage of participants with the best overall response of CR or PR to therapy and duration of time from start of treatment to time of progression or death, whichever occurs first.
Duration of response (DoR)
Time from start of treatment to disease progression or death in participants who achieve CR or PR
Overall survival (OS)
Time from the start of treatment that participants are still alive.
Progression-free survival (PFS)
Duration of time from start of treatment to time of progression or death, whichever occurs first
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