Renal Cell Carcinoma (RCC)
Conditions
Keywords
Renal cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor
Brief summary
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat compared to sunitinib or pazopanib in participants with locally advanced/metastatic renal cell carcinoma (mRCC) with a clear cell component who have not received prior systemic therapy for their mRCC.
Interventions
DRUGPembrolizumab
Pembrolizumab 200 mg administered intravenously every 3 weeks.
DRUGEpacadostat
Epacadostat 100 mg administered orally twice daily.
DRUGSunitinib
Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle.
DRUGPazopanib
Pazopanib 800 mg administered orally once daily.
Sponsors
Incyte Corporation
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features. * Must not have received any prior systemic therapy for their mRCC. * Measurable disease based on RECIST v1.1. * Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion as required. * Karnofsky performance status ≥ 70%. * Adequate organ function per protocol-defined criteria.
Exclusion criteria
* Use of protocol-defined prior/concomitant therapy. * Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization. * History of severe hypersensitivity reaction to study treatments or their excipients. * Active autoimmune disease that has required systemic treatment in past 2 years. * Known additional malignancy that has progressed or has required active treatment in the last 3 years. * Known active central nervous system metastases and/or carcinomatous meningitis. * History of (noninfectious) pneumonitis that required steroids or current pneumonitis. * History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful. * Significant cardiac event within 12 months before Cycle 1 Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | up to approximately 8 months | ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Experiencing Adverse Events (AEs) | Data reported from start of study to data cutoff 28-Feb-2019, up to 15 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 SOC as Measured by the Number of Participants Discontinuing Study Drug Due to AEs | Data reported from start of study to data cutoff 28-Feb-2019, up to 15 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, Brazil, Canada, Chile, France, Germany, Hungary, Ireland, Italy, Japan, New Zealand, Norway, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMark Jones, MD
Incyte Corporation
Participant flow
Recruitment details
This study was conducted at 73 centers in 14 countries.
Pre-assignment details
No new participants were enrolled after 02-MAY-2018. As the results did not meet statistical preplanned assumptions, the development of the combination therapy was stopped. At the time of discontinuation, participants were given the option to discontinue from the study or continue study treatment if they showed clinical benefit per investigators.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Epacadostat Pembrolizumab 200 mg administered intravenously every 3 weeks. Epacadostat 100 mg administered orally twice daily. | 64 |
| SoC (Sunitinib or Pazopanib) Standard of care (SoC) (sunitinib or pazopanib monotherapy). Sunitinib 50 mg administered orally once daily. Pazopanib 800 mg administered orally once daily. | 65 |
| Total | 129 |
Baseline characteristics
| Characteristic | Pembrolizumab + Epacadostat | SoC (Sunitinib or Pazopanib) | Total |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 10.9 | 62.1 years STANDARD_DEVIATION 10.6 | 62.5 years STANDARD_DEVIATION 10.7 |
| ECOG Performance Scale 0 | 41 Participants | 35 Participants | 76 Participants |
| ECOG Performance Scale 1 | 23 Participants | 28 Participants | 51 Participants |
| ECOG Performance Scale 2 | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 14 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 47 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 9 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 53 Participants | 56 Participants | 109 Participants |
| Sex: Female, Male Female | 20 Participants | 15 Participants | 35 Participants |
| Sex: Female, Male Male | 44 Participants | 50 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 64 | 8 / 65 |
| other Total, other adverse events | 61 / 64 | 61 / 63 |
| serious Total, serious adverse events | 18 / 64 | 15 / 63 |
Outcome results
Primary
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC)
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
Time frame: Minimum up to 6 months
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 the cutoff date 28FEB2019.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pembrolizumab + Epacadostat | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | Partial Response (PR) | 29.7 percentage of participants |
| Pembrolizumab + Epacadostat | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | Complete Response (CR) | 1.6 percentage of participants |
| Pembrolizumab + Epacadostat | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | Objective Response (CR+PR) | 31.3 percentage of participants |
| SoC (Sunitinib or Pazopanib) | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | Partial Response (PR) | 29.2 percentage of participants |
| SoC (Sunitinib or Pazopanib) | Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC) | Objective Response (CR+PR) | 29.2 percentage of participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to 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: Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.
Population: The All Subjects as Treated (ASaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Epacadostat | Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to AEs | 8 Participants |
| SoC (Sunitinib or Pazopanib) | Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to AEs | 6 Participants |
Secondary
Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the 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: Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.
Population: The All Subjects as Treated (ASaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Epacadostat | Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Experiencing Adverse Events (AEs) | 64 Participants |
| SoC (Sunitinib or Pazopanib) | Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Experiencing Adverse Events (AEs) | 63 Participants |