Phase 3 Study of Pembrolizumab with and without Epacadostat as a second treatment after a platinum containing chemotherapy for recurring or metastatic bladder cancer

Phase 1

• Conditions: Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients who have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease; MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002310-31-FR
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-12
• Last Update Posted: 13 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 648

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 <10) must be determined by the central laboratory prior to randomization. Participants will be excluded if PD-L1 status cannot be determined.
5. Have resolution of all toxicities and any toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). Participants with =Grade 2 neuropathy are an exception and may enroll.
6. Be =18 years of age on day of signing informed consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days prior to randomization.
Male participants:
8. A male participant must agree to use a contraception 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.
Female participants:
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 use contraception 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.
9. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
10. Have adequate organ function as defined in the protocol. Specimens 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 259
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 389

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 (

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified