Head and Neck Cancer, Lung Cancer, Solid Tumors, UC (Urothelial Cancer)
Conditions
Brief summary
The purpose of this study is to explore the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of INCB024360 administered in combination with MEDI4736 in subjects with selected advanced solid tumors.
Interventions
DRUGMEDI4736
MEDI4736 administered intravenously (IV) every two weeks (q2w)
DRUGINCB024360
INCB024360: Oral daily dosing
Sponsors
AstraZeneca
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, age 18 years or older * Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors * Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment
Exclusion criteria
* Laboratory and medical history parameters not within protocol-defined range * Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose * Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor (exception is tumor types in which a PD-1 pathway targeted agent is approved, e.g. melanoma, non-small cell lung cancer.) * Receipt of any anticancer medication in the 21 days prior to receiving the first dose of study medication * Has an active or inactive autoimmune process * Evidence of interstitial lung disease or active, non-infectious pneumonitis * Prior radiotherapy within 2 weeks of initiating treatment; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis * Untreated central nervous system (CNS) metastases or CNS metastases that have progressed * Currently pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | Duration of study treatment and up to 90 days after the last dose [approximately 3 years] | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment |
| Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Measured every 8 weeks for duration of study treatment [approximately 12 months] | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | Measured every 8 weeks for duration of active study treatment [approximately 24 months] | Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression. |
| Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | Measured every 8 weeks for duration of active study treatment [approximately 24 months] | — |
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | — |
| Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | Measured every 8 weeks for duration of study treatment [approximately 6 months] | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | — |
| Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks]. | — |
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | — |
| Phase 2: Number of Treatment-Emergent Adverse Events | Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years] | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 13 study sites in the United States. Participants were enrolled at 12 study sites.
Pre-assignment details
A total of 235 participants were screened and 59 participants were screen failures. A total of 176 participants ( 34 participants in Phase 1 and 142 in Phase 2) were enrolled in the study. Study enrollment was permanently discontinued on 24 Apr 2018 as a strategic decision. At the time of data cut-off, 28 Aug 2019, 1 participant was ongoing.
Participants by arm
| Arm | Count |
|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 6 |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 3 |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 4 |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 4 |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 8 |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | 9 |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | 49 |
| Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | 93 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 5 | 3 | 1 | 4 | 6 | 5 | 34 | 58 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 | 3 | 4 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Participant trial terminated by sponsor | 0 | 0 | 1 | 0 | 1 | 2 | 5 | 16 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Transitioned to Hospice | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 | 1 | 6 | 14 |
Baseline characteristics
| Characteristic | Total | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.3 Years STANDARD_DEVIATION 11.11 | 70.8 Years STANDARD_DEVIATION 4.79 | 75.7 Years STANDARD_DEVIATION 7.23 | 65.3 Years STANDARD_DEVIATION 9.07 | 72.3 Years STANDARD_DEVIATION 7.59 | 58.6 Years STANDARD_DEVIATION 8.65 | 63.4 Years STANDARD_DEVIATION 7.75 | 60.2 Years STANDARD_DEVIATION 13.24 | 64 Years STANDARD_DEVIATION 10.27 |
| Race/Ethnicity, Customized Asian | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 164 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 8 Participants | 9 Participants | 46 Participants | 87 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 157 Participants | 6 Participants | 3 Participants | 4 Participants | 4 Participants | 7 Participants | 9 Participants | 41 Participants | 83 Participants |
| Sex: Female, Male Female | 57 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants | 19 Participants | 25 Participants |
| Sex: Female, Male Male | 119 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 7 Participants | 4 Participants | 30 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 3 / 3 | 1 / 4 | 4 / 4 | 6 / 8 | 5 / 9 | 35 / 49 | 58 / 93 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 4 / 4 | 4 / 4 | 8 / 8 | 9 / 9 | 48 / 49 | 87 / 93 |
| serious Total, serious adverse events | 2 / 6 | 0 / 3 | 2 / 4 | 0 / 4 | 4 / 8 | 3 / 9 | 20 / 49 | 54 / 93 |
Outcome results
Primary
Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE)
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment
Time frame: Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Population: The Phase 1 safety population includes all subjects enrolled in the Phase 1 portion of the study who received at least 1 dose of INCB024360 or MEDI4736. Treatment groups were determined according to the actual treatment the subject received on Day 1 regardless of the actual study drug the subject received during participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 6 Participants |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 3 Participants |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 4 Participants |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 4 Participants |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 8 Participants |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | 9 Participants |
Primary
Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Measured every 8 weeks for duration of study treatment [approximately 12 months]
Population: Intent-to-Treat Population : All subjects who are enrolled in the Phase 2 portion of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 6 Participants |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 12 Participants |
Secondary
Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression
Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.
Time frame: Measured every 8 weeks for duration of active study treatment [approximately 24 months]
Population: Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 \& 2 portion of the study. Treatment groups were defined at the time of enrollment on Day 1 according to the treatment assignment for Phase 1 and according to the tumor type for phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | 1.9 months |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | NA months |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | NA months |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | NA months |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | 13.8 months |
| Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | NA months |
Secondary
Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs)
Time frame: Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks].
Population: Evaluable Patients Post-Baseline: Treatment-Induced ADA - Patients who had baseline negative ADA result who developed anti-drug antibodies at any time after initial drug administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 1 Participants |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
| Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) | 0 Participants |
Secondary
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve
Time frame: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Population: The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Arm/Group were combined with the data collected from participants in the Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Arm/Group for PK Analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 1040 h*nM | Standard Deviation 345 |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 1580 h*nM | Standard Deviation 739 |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 3090 h*nM | Standard Deviation 1880 |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 3650 h*nM | Standard Deviation 2710 |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 15400 h*nM | Standard Deviation 6770 |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 4130 h*nM | Standard Deviation 1960 |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve | 12200 h*nM | Standard Deviation 5950 |
Secondary
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration
Time frame: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Population: The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Arm/Group were combined with the data collected from participants in the Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Arm/Group for PK Analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 273 nM | Standard Deviation 65.3 |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 248 nM | Standard Deviation 135 |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 604 nM | Standard Deviation 493 |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 727 nM | Standard Deviation 403 |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 2660 nM | Standard Deviation 1200 |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 960 nM | Standard Deviation 499 |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration | 2500 nM | Standard Deviation 1190 |
Secondary
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration
Time frame: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Population: The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Arm/Group were combined with the data collected from participants in the Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Arm/Group for PK Analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 2.0 hours |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 2.0 hours |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 1.9 hours |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 2.0 hours |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 3.3 hours |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 2.0 hours |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration | 2.1 hours |
Secondary
Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death
Time frame: Measured every 8 weeks for duration of active study treatment [approximately 24 months]
Population: Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 \& 2 portion of the study. Treatment groups were defined at the time of enrollment on Day 1 according to the treatment assignment for Phase 1 and according to the tumor type for phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 2.4 Months |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 12.0 Months |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 1.9 Months |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 1.7 Months |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 4.1 Months |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 2.5 Months |
| Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 1.9 Months |
| Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death | 2.1 Months |
Secondary
Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Measured every 8 weeks for duration of study treatment [approximately 6 months]
Population: Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 portion of the study. Treatment groups for this population were defined according to the treatment assignment at the time of enrollment on Day 1 regardless of the actual study drug the subject received during his/her continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 1 Participants |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 0 Participants |
| Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 1 Participants |
| Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 0 Participants |
| Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 1 Participants |
| Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | 2 Participants |
Secondary
Phase 2: Number of Treatment-Emergent Adverse Events
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment
Time frame: Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Population: The Phase 2 safety population includes all subjects enrolled in the Phase 2 portion of the study who received at least 1 dose of INCB024360 or MEDI4736.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase 2: Number of Treatment-Emergent Adverse Events | 49 Participants |
| Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase 2: Number of Treatment-Emergent Adverse Events | 93 Participants |