UC (Urothelial Cancer)
Conditions
Keywords
Urothelial carcinoma, programmed cell death protein 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase (IDO) inhibitor
Brief summary
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.
Interventions
DRUGPembrolizumab
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.
DRUGEpacadostat
Epacadostat administered orally twice daily.
DRUGPlacebo
Matching placebo administered orally twice daily.
Sponsors
Merck Sharp & Dohme LLC
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type. * Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12 months following completion of therapy. * Measurable disease based on RECIST v1.1. * 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. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function per protocol-defined criteria.
Exclusion criteria
* Urothelial carcinoma that is suitable for local therapy with curative intent. * History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. * Known additional malignancy that is progressing or has required active treatment within the past 3 years. * 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. * Active autoimmune disease that has required systemic treatment in past 2 years. * Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority. * Known history of or is positive for active hepatitis B (HBsAg reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility. * Use of protocol-defined prior/concomitant therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | up to 9 weeks +14 days | ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) | Up to 8 months | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE | Up to 8 months | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
Countries
Australia, Canada, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Netherlands, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 82 centers in 16 countries.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab 200 mg + Epacadostat 100 mg BID Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Epacadostat administered orally twice daily. | 42 |
| Pembrolizumab 200 mg + Placebo BID Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. Matching placebo administered orally twice daily. | 42 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 13 | 13 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Pembrolizumab 200 mg + Epacadostat 100 mg BID | Pembrolizumab 200 mg + Placebo BID | Total |
|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 8.7 | 65.2 years STANDARD_DEVIATION 10 | 66.5 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 37 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 9 Participants |
| Metastasis Status at Screening Advanced/Unresectable | 7 Participants | 2 Participants | 9 Participants |
| Metastasis Status at Screening Metastatic | 35 Participants | 40 Participants | 75 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 35 Participants | 32 Participants | 67 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 35 Participants | 37 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 42 | 18 / 41 | 32 / 83 |
| other Total, other adverse events | 39 / 42 | 35 / 41 | 74 / 83 |
| serious Total, serious adverse events | 22 / 42 | 16 / 41 | 38 / 83 |
Outcome results
Primary
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
Time frame: up to 9 weeks +14 days
Population: The Intention-to-Treat (ITT) population consisted of all randomized participants. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to week 9 (day 63) + 14 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg + Epacadostat 100 mg BID | Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | 21.4 percentage of participants |
| Pembrolizumab 200 mg + Placebo BID | Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | 9.5 percentage of participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to 8 months
Population: All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg + Epacadostat 100 mg BID | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE | 4 Participants |
| Pembrolizumab 200 mg + Placebo BID | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE | 6 Participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)
AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to 8 months
Population: All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg + Epacadostat 100 mg BID | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) | 42 Participants |
| Pembrolizumab 200 mg + Placebo BID | Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) | 39 Participants |