Solid Tumors
Conditions
Keywords
Epacadostat, nivolumab, ipilimumab, lirilumab, solid tumor, melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), IDO inhibitor
Brief summary
The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.
Interventions
DRUGEpacadostat
Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.
DRUGNivolumab
Nivolumab at the protocol-specified dose and schedule.
DRUGIpilimumab
Ipilimumab at the protocol-specified dose and schedule.
DRUGLirilumab
Lirilumab at the protocol-specified dose and schedule.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* During Phase 1, participant with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment. * During Phase 2, participant with advanced cancer who have received at least one prior therapy or are treatment naive, depending on the specified tumor type. * Presence of measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Expected survival of ≥ 12 weeks.
Exclusion criteria
* Laboratory and medical history parameters not within the Protocol-defined range. * Receipt of anticancer medications or investigational drugs within Protocol-defined time frames. * Previous radiotherapy within 7 days of Cycle 1 Day 1. * Known active central nervous system metastases and/or carcinomatous meningitis. * Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor. * Active infection requiring systemic therapy. * Any active or inactive autoimmune disease or syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs) | Screening through up to 100 days after end of treatment, up to approximately 24 months | A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. |
| Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Progression-free Survival (PFS) | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. |
| Phase 2: Duration of Response (DOR) | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. |
| Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1 | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
| Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Screening through up to 100 days for treatment Group A and 150 days for treatment Group B after end of treatment, up to approximately 24 months | A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. |
| Phase 2: Progression-free Survival (PFS) | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. |
| Phase 1: Duration of Response (DOR) | Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24) | DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. |
Countries
United States
Participant flow
Recruitment details
Participants took part at 4 study centers in the United States from 21 March 2018 to 29 January 2021.
Pre-assignment details
Participants were to be enrolled in Phase 1: Dose escalation Phase which consisted of 2 Treatment Groups: A (epacadostat, nivolumab, ipilimumab) and B (epacadostat, nivolumab and lirilumab), followed by Phase 2: a tumor-specific cohort Dose expansion Phase, which was to begin when maximum tolerated dose (MTD)/pharmacologically active dose (PAD) of epacadostat was determined in Phase 1. However, the study was terminated prior to enrollment in Phase 1: Treatment Group B and Phase 2 cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months. | 5 |
| Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months. | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Reason not Specified | 3 | 4 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID | Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 8.79 | 53.8 years STANDARD_DEVIATION 8.57 | 59.1 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Height | 173.2 centimeter (cm) STANDARD_DEVIATION 9.2 | 174.2 centimeter (cm) STANDARD_DEVIATION 3.25 | 173.7 centimeter (cm) STANDARD_DEVIATION 6.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
| Weight | 90.464 kilogram (kg) STANDARD_DEVIATION 16.3665 | 81.255 kilogram (kg) STANDARD_DEVIATION 26.5702 | 85.441 kilogram (kg) STANDARD_DEVIATION 21.9832 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 5 | 2 / 6 | 3 / 11 |
| other Total, other adverse events | 5 / 5 | 6 / 6 | 11 / 11 |
| serious Total, serious adverse events | 2 / 5 | 3 / 6 | 5 / 11 |
Outcome results
Primary
Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.
Time frame: Screening through up to 100 days after end of treatment, up to approximately 24 months
Population: Safety population included all participants enrolled in the study who received at least 1 dose of combination therapy. Treatment group B was excluded from this analysis as no participants were enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID | Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID | Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs) | 100 percentage of participants |
Primary
Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 1: Duration of Response (DOR)
DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1
ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 1: Progression-free Survival (PFS)
PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 2: Duration of Response (DOR)
DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.
Time frame: Screening through up to 100 days for treatment Group A and 150 days for treatment Group B after end of treatment, up to approximately 24 months
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.
Secondary
Phase 2: Progression-free Survival (PFS)
PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Population: As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.