A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Subjects with High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy
- Conditions
- Bladder Cancer10038364
- Registration Number
- NL-OMON46995
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
1. Have a histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, High Grade Ta and/or CIS) transitional cell carcinoma of the bladder.
2. In subjects who have papillary tumors (Ta and T1), a complete TURBT must have been performed, as per protocol.
3. Have been treated with adequate BCG therapy and have developed high risk NMBIC that is unresponsive to BCG therapy.
4. Have elected not to undergo, or are considered ineligible for radical cystectomy, as determined by the treating surgeon.
5. Have provided tissue for biomarker analysis from the most recent cystoscopy/TURBT procedures, from which tumor sample is available.
6. Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale. (Max of 5% ECOG of 2.)
7. Demonstrate adequate organ function.
8. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and be willing to use contraception in accordance with Section 5.7.2 of Protocol.
1. Has muscle invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
2. Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
3. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
4. Has undergone any intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting trial treatment.
5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1, Day 1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to a previously administered agent.
6. Has a known additional malignancy that is progressing or requires active treatment.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years.
8. Has a diagnosis of immunidefiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor.
9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
10. Has an active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI) in the last month.
11. Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
14. Has known active Hepatitis B or Hepatitis C.
15. Has received a live virus vaccine within 30 days of planned start of trial treatment.
16. Has had an allogenic tissue/solid organ transplant.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Complete response (CR) for patients in cohort A and disease free survival (DFS)<br /><br>of high risk NMIBC for patients in cohort B, as assessed by central pathology<br /><br>and radiology review, will be used as the primary efficacy endpoints.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Apart from complete response / disease free survival:<br /><br>- Response duration<br /><br>- PD-L1 expression<br /><br>- Overall Survival<br /><br>- Progression free survival (PFS)</p><br>