Phase 1/2 Substudy of Investigation Agents in PD-1/L1 Refractory Locally Advanced (Inoperable) or Metastatic Urothelial (Bladder) Cancer
- Conditions
- ocally advanced or metastatic urothelial cancerMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004544-28-IT
- Lead Sponsor
- MERCK SHARP & DOHME LLC. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
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 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 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). If the participant received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity (resolved to = Grade 1) and/or complications from the intervention.
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 years of age at the time of providing documented informed c
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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To assess the safety and tolerability of investigational treatments<br>2. To evaluate objective response rate (ORR) of each investigational treatment arm as assessed by BICR per RECIST 1.1<br>;Secondary Objective: 1. To evaluate the duration of response (DOR) of each investigational treatment arm as assessed by BICR per RECIST 1.1;Primary end point(s): 1. Percentage of Participants Who Experienced At Least One Adverse Event (AE)<br>2. Percentage of Participants Who Discontinued Study Treatment Due to an AE<br>3. Objective Response Rate (ORR) ;Timepoint(s) of evaluation of this end point: 1. Up to approximately 5 years<br>2. Up to approximately 5 years<br>3. Up to approximately 2 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Duration of Response (DOR) ;Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years