bladder cancer inoperable or metastatic UC
Conditions
Interventions
The total number of investigational treatment arms will depend on the number of
investigational agents evaluated. This study protocol will include
a minimum of 1 investigational treatment arm (arm A)
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Has a histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra. Participants with nonurothelial tumors,including pure squamous cell carcinoma, pure adenocarcinoma including urachal adenocarcinomas, neuroendocrine tumors, and mesenchymal tumors, are not eligible. 2. Has measurable disease as assessed by the site and verified by blinded independent central review (BICR) according to RECIST 1.1. 3. Has PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. In these participants, anti-PD-1/L1 mAb treatment is defined by meeting ALL of the following criteria: a. Has received at least 2 doses of an approved anti-PD-1/L1 mAb. b. Has demonstrated radiographic disease progression while on treatment or after treatment with an anti-PD-1/L1 mAb by investigator assessment. c. Disease progression has been documented radiographically by the investigator within 12 weeks from the last dose of anti-PD-1/L1 mAb. OR Has experienced disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive UC (MIUC) administered as monotherapy. In these participants, anti-PD-1/L1 mAb treatment is defined by meeting ALL of the following criteria: a. Has received at least 2 doses of an approved anti-PD-1/L1 mAb. b. Has demonstrated radiographic disease recurrence while on treatment with an anti-PD-1/L1 mAb or within 6 months from treatment completion by investigator assessment. 4. Participants who received an anti-PD-1/L1 mAb for the treatment of locally advanced/unresectable or mUC must have demonstrated disease progression while on treatment or after treatment with an anti-PD-1/L1 mAb based on investigator assessment. If available, scans before treatment with an anti-PD-1/L1 or showing nadir during treatment with an anti-PD-1/L1 mAb and scans that document radiographic disease progression within 12 weeks (84 days) from the last dose of an anti-PD-1/L1 mAb should be submitted to the iCRO. Participants who received an anti-PD-1/L1 mAb for the treatment of MIUC must have demonstrated disease recurrence while on treatment or within 6 months from treatment completion based on investigator assessment. If available, scan before treatment with an anti-PD-1/L1 mAb and scan that documents radiographic recurrence should be submitted to the iCRO. 5. Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable. 6. Has an ECOG performance status of 0 to 1 (as assessed within 7 days of the first dose of study intervention). 7. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). 8. Has adequate organ function. Specimens must be collected within 7 days before the start of study intervention. 9. Participants are male or female, >=18 ye
Exclusion criteria
Exclusion criteria: 1. Has a known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation. 2. Has known active CNS metastases and/or carcinomatous meningitis. 3. Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with pembrolizumab or other investigational agents being evaluated within this study. 4. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation. 5. Has an active infection requiring systemic therapy. 6. Has received prior radiotherapy within 2 weeks of first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 7. Has had major surgery (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Adverse Events (AEs) - Study intervention discontinuations due to AEs. - Objective Response (OR): Complete response (CR) or partial response (PR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (DOR): For participants who demonstrate CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. | — |
Countries
Netherlands
Outcome results
None listed