A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants with PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A
- Conditions
- bladder cancerinoperable or metastatic UC1002765610004994
- Registration Number
- NL-OMON51831
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
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
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 (<3 weeks before first dose of study intervention).
8. Has received a live or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of killed vaccines are allowed.
9. Is currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 4 weeks
before the first dose of study intervention.
10. Has known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
11. Has known history of hepatitis B (defined as HBsAg reactive) or known
hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
12. Has a history or has current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere
with the participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the
treating investigator.
13. Has had an allogeneic tissue/solid organ transplant.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Adverse Events (AEs)<br /><br>- Study intervention discontinuations due to AEs.<br /><br>- Objective Response (OR): Complete response (CR) or partial response (PR)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Duration of response (DOR): For participants who demonstrate CR or PR, DOR is<br /><br>defined as the time from the first documented evidence of CR or PR until<br /><br>disease progression or death due to any cause, whichever occurs first.</p><br>