Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients who have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma 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-confirmed diagnosis of UC of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type. 2. Have progression or recurrence of UC following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. No additional lines of systemic treatment are allowed. 3. Have the presence of at least one measurable lesion by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 as determined by the investigator/local radiology assessment. a. If participants have only 1 measurable lesion per RECIST 1.1, any biopsy specimen should be obtained from the non-target lesion or archival tissue. b. If participants have only 1 measurable lesion per RECIST 1.1, this lesion should not have been in the field of prior irradiation unless there is documented progression of the lesion(s). 4. Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for PD-L1 analysis. A newly obtained biopsy is strongly preferred but not required if archival tissue is adequate for analysis. If submitting unstained cut slides, freshly cut slides should be submitted to the central laboratory within 14 days from when the slides are cut. Refer to Section 9.8.1 in the protocol for an explanation. PD-L1 status (CPS =10 or CPS =65 years) yes F.1.3.1 Number of subjects for this age range 389
Exclusion criteria
Exclusion criteria: 1. Has urothelial carcinoma that is suitable for local therapy with curative intent. 2. Has presence of a gastrointestinal condition that in the opinion of the Investigator may affect drug absorption. 3. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted. 4. 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 msec is excluded (corrected by Fridericia formula 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. 5. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's 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. 6. 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. 7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, (note that repeat imaging should be performed during the study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 9. Has severe hypersensitivity (=Grade 3) to study treatment (pembrolizumab and epacadostat) and/or any of its excipients. 10. 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. 11. Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA). 12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study. 16. A WOCBP who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 17. 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 (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate and compare overall survival (OS) of participants treated with pembrolizumab plus epacadostat to those treated with pembrolizumab plus placebo. - To evaluate and compare progression-free survival (PFS) of participants treated with pembrolizumab plus epacadostat to those treated with pembrolizumab plus placebo.;Secondary Objective: - To evaluate and compare ORR of participants treated with pembrolizumab plus epacadostat to those treated with pembrolizumab plus placebo. - To evaluate and compare the safety and tolerability of participants treated with pembrolizumab plus epacadostat to those treated with pembrolizumab plus placebo. - To evaluate and compare mean change from baseline and time to true deterioration (TTD) in global health status/Quality of Life (QoL), in both treatment groups.;Primary end point(s): 1) Overall survival (OS) 2) Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) by investigator determination;Timepoint(s) of evaluation of this end point: Two analyses (one interim and one final) are planned in this study. The interim will be performed when approximately 483 total PFS events are observed, which is expected to occur at ~19 months after study start (first participant randomized). The final analysis is to be performed after approximately 355 total OS events are observed, which is expected to occur at ~27 months after study start. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective Response Rate (ORR) per RECIST 1.1 assessed by investigator determination;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analyzed at the time of the final analysis at ~27 months after study start. | — |
Countries
Australia, Canada, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactMei Chen
Incyte Corporation
Outcome results
None listed