This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants.
Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).
It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.
Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
Sequential
disitamab vedotin
DrugGiven into the vein (IV; intravenous) every 2 weeks.
pembrolizumab
DrugGiven by IV on Day 1 of each 6-week cycle.
8
Treatment groupsSee each treatment group below.
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, C, and G)
The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1
Incidence of adverse events (AEs) (Cohorts D and E)
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Incidence of dose alterations (Cohorts D and E)
Incidence of laboratory abnormalities (Cohorts D and E)
To be summarized using descriptive statistics.
cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G)
The proportion of participants with confirmed CR or PR according to RECIST v1.1
Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, C, and G)
The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.
Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G)
The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.
Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, C, and G)
The time from the start of study treatment or randomization (if applicable) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.
Click on the lead sponsor to view all of their trials.
Seagen, a wholly owned subsidiary of Pfizer
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
