Bladder cancer MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Interventions
Product Name: pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Both transitional cell and mixed transitional/non-transitional (predominantly transitional) cell histologies are allowed. Participants with non-urothelial cancer of the urinary tract are not allowed. 2. Have measureable disease based on RECIST 1.1 as assessed by the local site investigator/radiology. Tumor lesions situated in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions. 3. Be considered ineligible to receive cisplatin-based combination therapy, based on having at least one of the following criteria: a. ECOG PS of 2 within 14 days prior to randomization (the proportion of participants with an ECOG PS of 2 will be limited to approximately 50% of the total population) b. CrCl (calculated or measured) 12 months from completion of therapy is permitted. OR b. Neoadjuvant platinum based chemotherapy, with recurrence >12 months since completion of therapy is permitted. 6. Be =18 years of age on day of signing informed consent. 7. Have a PS of 0, 1 or 2 within 14 days prior to randomization on the ECOG Performance Scale. 8. A male participant must agree to use a contraception as detailed in the protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. 9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatments (MK-3475 and epacadostat) after the last dose of study treatment. 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 11. Demonstrate adequate organ function as defined in the protocol. All screening labs must be collected within 14 days prior to randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: 1. Has disease that is suitable for local therapy administered with curative intent. 2. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 3. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 4. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. 6. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 7. Has an active infection requiring systemic therapy. 8. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. 9. Has known history of or is positive for active Hepatitis B (Hepatitis B surface antigen [HBsAg] reactive) or has active Hepatitis C (HCV RNA). 10. Has a history of a gastrointestinal condition or procedure that in the opinion of the Investigator may affect oral drug absorption. 11. Has a history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT interval (QTc) interval >480 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is >480 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is <480 milliseconds. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study. 14. A WOCBP who has a positive urine pregnancy test within 72 hours before randomization. If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 15. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of pembrolizumab and epacadostat/matching placebo. 16. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti PD-L2 agent, IDO1 inhibitor, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting. 17. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. 18. Has received prior radiotherapy within 2 weeks of start of trial treatment. Participants must have recovered from all radiation-related toxicities, and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To estimate the ORR of pembrolizumab plus epacadostat and pembrolizumab plus placebo based on RECIST 1.1 by investigator determination.;Secondary Objective: - To evaluate the safety and tolerability of pembrolizumab plus epacadostat versus pembrolizumab plus placebo. ;Primary end point(s): - ORR - defined as the proportion of participants in the analysis population who have a best response of complete response (CR) or partial response (PR);Timepoint(s) of evaluation of this end point: There is no interim analysis. During the course of the study, DMC will perform 1 safety review based on the DMC charter. The final analysis will be performed after the last participant completes the Week 9 imaging assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Adverse events (AEs) - Study drug discontinuations due to AEs;Timepoint(s) of evaluation of this end point: There is no interim analysis. During the course of the study, DMC will perform 1 safety review based on the DMC charter. The final analysis will be performed after the last participant completes the Week 9 imaging assessment. | — |
Countries
Australia, Belgium, Brazil, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactKapadia
Ekta
Outcome results
None listed