Bladder Cancer, Colorectal Cancer (CRC), Gastric Cancer, Head and Neck Cancer, Lung Cancer, Mesothelioma, Metastatic Cancer, Renal Cell Carcinoma (RCC), Solid Tumors, UC (Urothelial Cancer)
Conditions
Keywords
Immuno-Oncology, Checkpoint Inhibitors, Tumor Metabolism, Programmed cell death protein-1 (PD-1) inhibitor, Programmed death ligand 1 (PD-L1) inhibitor, Solid Tumors, RCC, MEL, NSCLC, Arginase, Arginase Inhibitor, INCB001158 (CB-1158), SCCHN, GEJ, Immune Therapy
Brief summary
This study is an open-label Phase 1/Phase 2 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.
Detailed description
This study is an open-label Phase 1 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors. Single Agent INCB001158: Patients with advanced/metastatic solid tumors will be enrolled into escalating monotherapy dose cohorts to determine the Recommended Phase 2 Dose (RP2D) of INCB001158. Additional patients with NSCLC, Colorectal Cancer (CRC), and other tumors including SCCHN, RCC, Gastric, Bladder and Melanoma will be enrolled at the single agent RP2D. Combination Treatment: Patients with advanced/metastatic NSCLC, Melanoma, Urothelial, Microsatellite Instability (MSI)/ Microsatellite Stable (MSS) CRC, Gastric, SCCHN and Mesothelioma will be enrolled into separate cohorts of combination therapy (INCB001158 and Pembrolizumab) to determine the RP2D. In the dose expansion phase, additional patients with NSCLC, Melanoma, Urothelial, MSI/MSS CRC, Gastric, SCCHN and Mesothelioma will be treated with the combination of INCB001158 and Pembrolizumab at the RP2D. All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.
Interventions
DRUGINCB001158
Arginase Inhibitor
DRUGPembrolizumab
PD-1 Inhibitor
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\*Additional cohort specific criteria may apply Inclusion Criteria: * Must be age 18 or older * Ability to provide written informed consent in accordance with federal, local, and institutional guidelines * Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 * Life Expectancy of at least 3 months * Adequate hepatic, renal (moderately impaired renal function in cohort 1c only), cardiac, and hematologic function * Measurable disease by RECISTv1.1 criteria * Resolution of treatment-related toxicities * Willingness to avoid pregnancy or fathering children * Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3a - 3d
Exclusion criteria
* Currently pregnant or lactating * Unable to receive oral medications * Unable to receive oral or IV hydration * Intolerance to prior anti-PD-1/PD-L1 therapy * Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3e - 3h * Prior severe hypersensitivity reaction to another monoclonal antibody (mAb) * Any other current or previous malignancy within 3 years except protocol allowed malignancies * Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks * Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy) * Active known or suspected exclusionary autoimmune disease * Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks * Concomitant therapy with valproic acid/valproate-containing therapies * Concomitant therapy with allopurinol and other xanthine oxidase inhibitors * History of known risks factors for bowel perforation * Symptomatic ascites or pleural effusion * Major surgery within 28 days before Cycle 1 Day 1 * Active infection requiring within 2 weeks prior to first dose of study drug * Patients who have HIV, Hepatitis B or C * Conditions that could interfere with treatment or protocol-related procedures * Active, non-stable brain metastases or CNS disease * Known deficiencies or suspected defect in the urea cycle * Received live-virus vaccination within 30 days (seasonal flu vaccine allowed if non-live virus) * NSCLC with EGFR or ALK mutation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to study completion (up to approximately 3.5 years) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study treatment(s). A TEAE was defined as any adverse event that started or worsened after the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RP2D of INCB001158 in Combination With Pembrolizumab | 12 weeks | INCB001158 was dosed orally BID. |
| Objective Response Rate (ORR) | Until disease progression/study discontinuation (up to approximately 5 years) | ORR was defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at any post-Baseline visits prior to first disease progression and alternative cancer therapy use. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma was evaluated using modified RECIST criteria. Confidence intervals were calculated based on the exact method for binomial distributions (Clopper Pearson). Two participants evaluable for PFS were not evaluable for response. |
| Tmax of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | tmax was defined as the time of the maximum observed concentration of INCB001158. |
| CL/F of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | CL/F was defined as the apparent oral dose clearance of INCB001158. |
| AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t. |
| AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | AUC0-inf was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 extrapolated to infinity. |
| t1/2 of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | t1/2 was defined as the half-life of INCB001158. |
| Percentage of Participants With the Indicated Best Overall Response (BOR) | Until disease progression/study discontinuation (up to approximately 5 years) | BOR was evaluated per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Stable disease (SD): no change in target lesions to qualify for CR, PR, or progressive disease (PD). PD: progression of a target or non-target lesion or presence of a new lesion. Missing: participant had a missing BOR because there were no post-Baseline tumor assessments. Pleural mesothelioma was evaluated using modified RECIST criteria. |
| Duration of Response (DOR) | Until disease progression/study discontinuation (up to approximately 5 years) | DOR was defined as the number of months from the date of the first documentation of an objective response (CR or PR per RECIST v1.1) to the date of the first documentation of disease progression or death, whichever occurred first. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma will be evaluated using modified RECIST criteria. Kaplan-Meier (KM) product-limit estimates with a log-log transformation were used for 95% confidence interval calculation. |
| Progression-free Survival (PFS) | Until disease progression/study discontinuation (up to approximately 5 years) | PFS was defined as the length of time between the date of the first dose and the earlier of death or progressive disease as assessed by RECIST v1.1. Pleural mesothelioma was evaluated using modified RECIST criteria. Participants enrolled in Part 1c had renal impairment. These participants received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. In renally impaired participants, the 50 mg dose has comparable exposure to 100 mg in participants with normal renal function. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function. |
| Cmax of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | Cmax was defined as the maximum observed concentration of INCB001158. |
| Vz/F of INCB001158 Following Single Escalating Doses for Part 1A | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose | Vz/F was defined as the apparent volume of distribution of INCB001158. |
| Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | Cmax was defined as the maximum observed concentration of INCB001158. |
| Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | tmax was defined as the time of the maximum observed concentration of INCB001158. |
| Recommended Phase 2 Dose (RP2D) of INCB001158 | 12 weeks | The RP2D was determined by a traditional 3+3 dose-escalation design of single-agent INCB001158 in participants with advanced/metastatic solid tumors at doses of 50, 75, 100, or 150 mg. |
| AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period. |
| t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | t1/2 was defined as the half-life of INCB001158. |
| CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | CL/F was defined as the apparent oral dose clearance of INCB001158. |
| Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | Vz/F was defined as the apparent volume of distribution of INCB001158. |
| Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose | Cmax was defined as the maximum observed concentration of INCB001158. |
| Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose | tmax was defined as the time of the maximum observed concentration of INCB001158. |
| AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose | AUC was defined as the area under the concentration-time curve of INCB001158. |
| Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose | Cmax was defined as the maximum observed concentration of INCB001158. |
| Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose | tmax was defined as the time of the maximum observed concentration of INCB001158. |
| AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose | AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t. |
| AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose | AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period. |
| Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose. | Cmax was defined as the Maximum observed concentration of INCB001158. |
| Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose. | tmax was defined as the time of the maximum observed concentration of INCB001158. |
| AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose | AUC0-8h was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to 8 hours post-dose. |
| AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A | Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose | AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t. |
Countries
Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
This global study (United States, Spain, and Italy) consisted of 3 parts: Part 1 was dose-escalation using a 3 + 3 design to determine the RP2D of INCB001158 as monotherapy (Part 1a) and in combination with pembrolizumab (Parts 1b and 1c); Part 2 and Part 3 consisted of tumor expansion cohorts to determine whether INCB001158 as monotherapy (Part 2) or in combination with pembrolizumab (Part 3) had sufficient antitumor activity and further evaluated the safety and tolerability of the RP2D.
Pre-assignment details
260 enrolled participants: 107 in the Part 1a and Part 2 monotherapy groups; 147 in the Part 1b and Part 3 combination therapy groups; and 6 in Part 1c. Disposition data have been reported by dose level; efficacy data have been reported by tumor type, regardless of dose received. One Part 3 participant scheduled to receive INCB001158 100 mg actually received 75 mg; they were included in the Part 1b 75 mg arm for disposition analysis and in the Part 1c and Part 3 100 mg arm for efficacy analysis.
Participants by arm
| Arm | Count |
|---|---|
| Part 1A: INCB001158 50 mg INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors. | 8 |
| Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors. | 7 |
| Part 1A and Part 2: INCB001158 100 mg INCB001158 was administered orally at 100 mg BID in participants with advanced/metastatic solid tumors. | 85 |
| Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors. | 7 |
| Part 1B: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W). | 10 |
| Part 1B: INCB001158 75 mg + Pembrolizumab INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W. | 14 |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W. | 123 |
| Part 1C: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function. | 6 |
| Total | 260 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Clinical Disease Progression | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Completed Follow-up Period | 0 | 0 | 6 | 2 | 1 | 0 | 9 | 1 |
| Overall Study | Consented to/Considered Other Clinical Study | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 9 | 0 | 1 | 3 | 24 | 2 |
| Overall Study | Didn't Return to Site | 1 | 0 | 1 | 1 | 0 | 0 | 2 | 0 |
| Overall Study | Discontinued per Sponsor/Participant Agreement | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Entered/Referred to Hospice Care | 1 | 1 | 8 | 0 | 0 | 0 | 4 | 0 |
| Overall Study | Follow-up Did Not Occur | 0 | 1 | 1 | 0 | 2 | 0 | 8 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | New Cancer Therapy | 2 | 2 | 21 | 4 | 3 | 6 | 56 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 | 4 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Refused Further Treatment/Contact | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Symptomatic Deterioration | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Systemic Treatment Options Necessary | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Taken off Treatment per Protocol | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 28 | 0 | 1 | 2 | 12 | 0 |
Baseline characteristics
| Characteristic | Part 1A: INCB001158 50 mg | Part 1A: INCB001158 75 mg | Part 1A and Part 2: INCB001158 100 mg | Part 1A: INCB001158 150 mg | Part 1B: INCB001158 50 mg + Pembrolizumab | Part 1B: INCB001158 75 mg + Pembrolizumab | Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Part 1C: INCB001158 50 mg + Pembrolizumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 3.96 | 61.7 years STANDARD_DEVIATION 6.1 | 61.4 years STANDARD_DEVIATION 10.42 | 67.0 years STANDARD_DEVIATION 8.12 | 58.7 years STANDARD_DEVIATION 11.64 | 62.8 years STANDARD_DEVIATION 10.81 | 59.7 years STANDARD_DEVIATION 11.94 | 73.3 years STANDARD_DEVIATION 7.69 | 60.9 years STANDARD_DEVIATION 10.9 |
| Race/Ethnicity, Customized American Indican/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 11 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 18 Participants |
| Race/Ethnicity, Customized Captured as Other in Database | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 1 Participants | 10 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants | 0 Participants | 21 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants | 6 Participants | 75 Participants | 6 Participants | 10 Participants | 14 Participants | 114 Participants | 6 Participants | 237 Participants |
| Race/Ethnicity, Customized White or Causasian | 5 Participants | 7 Participants | 70 Participants | 6 Participants | 9 Participants | 13 Participants | 109 Participants | 5 Participants | 224 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 39 Participants | 4 Participants | 6 Participants | 3 Participants | 43 Participants | 3 Participants | 109 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 46 Participants | 3 Participants | 4 Participants | 11 Participants | 80 Participants | 3 Participants | 151 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 | 0 / 8 | 0 / 7 | 12 / 85 | 0 / 7 | 3 / 16 | 3 / 14 | 24 / 123 | 42 / 260 |
| other Total, other adverse events | 7 / 8 | 7 / 7 | 77 / 85 | 7 / 7 | 16 / 16 | 13 / 14 | 116 / 123 | 243 / 260 |
| serious Total, serious adverse events | 3 / 8 | 2 / 7 | 31 / 85 | 0 / 7 | 6 / 16 | 5 / 14 | 47 / 123 | 94 / 260 |
Outcome results
Primary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study treatment(s). A TEAE was defined as any adverse event that started or worsened after the first dose of study drug.
Time frame: up to study completion (up to approximately 3.5 years)
Population: Safety Population: all participants who received at least 1 dose of INCB001158 or pembrolizumab. Data collected through study completion have been reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Part 1A: INCB001158 75 mg | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Part 1A: INCB001158 100 mg | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 81 Participants |
| Part 1A: INCB001158 150 mg | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 10 Participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 13 Participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 123 Participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 6 Participants |
Secondary
AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
AUC0-8h was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to 8 hours post-dose.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
Population: PK Population. Only participants with available data were analyzed. Analysis was conducted to compare INCB001158 50 mg + pembrolizumab in participants with renal impairment with INCB001158 50 mg or 75 mg in participants with normal renal function. It was pre-specified to collect data for only the Part 1A INCB001158 50 mg, Part 1A: INCB001158 75 mg, and Part 1C: INCB001158 50 mg + Pembrolizumab arms. Participants in the INCB001158 100 mg and 150 mg arms did not contribute to the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 4480 hours x ng/mL | Geometric Coefficient of Variation 0.29 |
| Part 1A: INCB001158 75 mg | AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 7890 hours x ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1B: INCB001158 50 mg + Pembrolizumab | AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 5210 hours x ng/mL | Geometric Coefficient of Variation 0.29 |
Secondary
AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A
AUC0-inf was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 extrapolated to infinity.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A | 8360 hours x ng/mL | Geometric Coefficient of Variation 0.35 |
| Part 1A: INCB001158 75 mg | AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A | 14100 hours x ng/mL | Geometric Coefficient of Variation 0.38 |
| Part 1A: INCB001158 100 mg | AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A | 16000 hours x ng/mL | Geometric Coefficient of Variation 0.42 |
| Part 1A: INCB001158 150 mg | AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A | 24400 hours x ng/mL | Geometric Coefficient of Variation 0.34 |
p-value: 0.6167ANOVA
90% CI: [0.82, 1.255]
90% CI: [0.849, 1.281]
90% CI: [0.945, 1.447]
Secondary
AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A
AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A | 8250 hours x ng/mL | Geometric Coefficient of Variation 0.27 |
| Part 1A: INCB001158 75 mg | AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A | 16600 hours x ng/mL | Geometric Coefficient of Variation 0.39 |
| Part 1A: INCB001158 100 mg | AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A | 18300 hours x ng/mL | Geometric Coefficient of Variation 0.34 |
| Part 1A: INCB001158 150 mg | AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A | 29700 hours x ng/mL | Geometric Coefficient of Variation 0.31 |
p-value: 0.1705ANOVA
90% CI: [0.863, 1.359]
90% CI: [0.719, 1.132]
90% CI: [0.945, 1.554]
Secondary
AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period.
Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Capsule | 18000 hours x ng/mL | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 50 mg | AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet | 17200 hours x ng/mL | Geometric Coefficient of Variation 0.28 |
Comparison: Tablet (test) versus Capsule (reference)p-value: 0.770790% CI: [0.712, 1.277]ANOVA
Secondary
AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A
AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A | 7910 hours x ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1A: INCB001158 75 mg | AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A | 15000 hours x ng/mL | Geometric Coefficient of Variation 0.35 |
| Part 1A: INCB001158 100 mg | AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A | 16200 hours x ng/mL | Geometric Coefficient of Variation 0.38 |
| Part 1A: INCB001158 150 mg | AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A | 28100 hours x ng/mL | Geometric Coefficient of Variation 0.32 |
p-value: 0.1723ANOVA
90% CI: [0.941, 1.42]
90% CI: [0.794, 1.198]
90% CI: [1.012, 1.503]
Secondary
AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A
AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A | 7700 hours x ng/mL | Geometric Coefficient of Variation 0.32 |
| Part 1A: INCB001158 75 mg | AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A | 13200 hours x ng/mL | Geometric Coefficient of Variation 0.34 |
| Part 1A: INCB001158 100 mg | AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A | 14200 hours x ng/mL | Geometric Coefficient of Variation 0.37 |
| Part 1A: INCB001158 150 mg | AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A | 21500 hours x ng/mL | Geometric Coefficient of Variation 0.35 |
p-value: 0.2867ANOVA
90% CI: [0.825, 1.23]
90% CI: [0.892, 1.311]
90% CI: [1.011, 1.507]
Secondary
AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.
Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Capsule | 20800 hours x ng/mL | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 50 mg | AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet | 19700 hours x ng/mL | Geometric Coefficient of Variation 0.27 |
Comparison: Tablet (test) versus Capsule (reference)p-value: 0.751490% CI: [0.718, 1.261]ANOVA
Secondary
AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
AUC was defined as the area under the concentration-time curve of INCB001158.
Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
Population: PK Population. Only participants with available date were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: INCB001158 50 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 6030 hours x ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1A: INCB001158 50 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 55550 hours x ng/mL | Geometric Coefficient of Variation 0.44 |
| Part 1A: INCB001158 75 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 11000 hours x ng/mL | Geometric Coefficient of Variation 0.27 |
| Part 1A: INCB001158 75 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 11900 hours x ng/mL | Geometric Coefficient of Variation 0.37 |
| Part 1A: INCB001158 100 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 13100 hours x ng/mL | Geometric Coefficient of Variation 0.31 |
| Part 1A: INCB001158 100 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 13100 hours x ng/mL | Geometric Coefficient of Variation 0.35 |
| Part 1A: INCB001158 150 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 22100 hours x ng/mL | Geometric Coefficient of Variation 0.29 |
| Part 1A: INCB001158 150 mg | AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 16400 hours x ng/mL | Geometric Coefficient of Variation 0.89 |
Comparison: Fed versus Fastedp-value: 0.70590% CI: [0.62, 1.363]ANOVA
Comparison: Fed versus Fastedp-value: 0.70390% CI: [0.658, 1.31]ANOVA
Comparison: Fed versus Fastedp-value: 0.995290% CI: [0.725, 1.377]ANOVA
Comparison: Fed versus Fastedp-value: 0.401290% CI: [0.394, 1.397]ANOVA
Secondary
CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A
CL/F was defined as the apparent oral dose clearance of INCB001158.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 6060 Liters per hour | Geometric Coefficient of Variation 0.27 |
| Part 1A: INCB001158 75 mg | CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 4510 Liters per hour | Geometric Coefficient of Variation 0.39 |
| Part 1A: INCB001158 100 mg | CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 5470 Liters per hour | Geometric Coefficient of Variation 0.34 |
| Part 1A: INCB001158 150 mg | CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 5050 Liters per hour | Geometric Coefficient of Variation 0.31 |
Secondary
CL/F of INCB001158 Following Single Escalating Doses for Part 1A
CL/F was defined as the apparent oral dose clearance of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | CL/F of INCB001158 Following Single Escalating Doses for Part 1A | 5980 Liters per hour | Geometric Coefficient of Variation 0.35 |
| Part 1A: INCB001158 75 mg | CL/F of INCB001158 Following Single Escalating Doses for Part 1A | 5330 Liters per hour | Geometric Coefficient of Variation 0.38 |
| Part 1A: INCB001158 100 mg | CL/F of INCB001158 Following Single Escalating Doses for Part 1A | 6240 Liters per hour | Geometric Coefficient of Variation 0.42 |
| Part 1A: INCB001158 150 mg | CL/F of INCB001158 Following Single Escalating Doses for Part 1A | 6150 Liters per hour | Geometric Coefficient of Variation 0.34 |
Secondary
Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A
Cmax was defined as the maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 987 ng/mL | Geometric Coefficient of Variation 0.28 |
| Part 1A: INCB001158 75 mg | Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 1880 ng/mL | Geometric Coefficient of Variation 0.28 |
| Part 1A: INCB001158 100 mg | Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 1990 ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1A: INCB001158 150 mg | Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 3370 ng/mL | Geometric Coefficient of Variation 0.3 |
p-value: 0.0745ANOVA
90% CI: [0.947, 1.341]
90% CI: [0.833, 1.18]
90% CI: [1.064, 1.486]
Secondary
Cmax of INCB001158 Following Single Escalating Doses for Part 1A
Cmax was defined as the maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: Pharmacokinetic (PK) Population: all participants who received at least 1 dose of INCB001158 or pembrolizumab and contributed at least 1 PK sample
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 Following Single Escalating Doses for Part 1A | 763 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0.3 |
| Part 1A: INCB001158 75 mg | Cmax of INCB001158 Following Single Escalating Doses for Part 1A | 1310 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0.26 |
| Part 1A: INCB001158 100 mg | Cmax of INCB001158 Following Single Escalating Doses for Part 1A | 1420 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0.3 |
| Part 1A: INCB001158 150 mg | Cmax of INCB001158 Following Single Escalating Doses for Part 1A | 1990 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 0.33 |
p-value: 0.0731ANOVA
90% CI: [0.784, 1.11]
90% CI: [0.908, 1.271]
90% CI: [1.034, 1.463]
Secondary
Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
Cmax was defined as the maximum observed concentration of INCB001158.
Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Capsule | 2170 ng/mL | Geometric Coefficient of Variation 0.23 |
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet | 2150 ng/mL | Geometric Coefficient of Variation 0.29 |
Comparison: Tablet (test) versus Capsule (reference)p-value: 0.962390% CI: [0.729, 1.349]ANOVA
Secondary
Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
Cmax was defined as the Maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.
Population: PK Population. Analysis was conducted to compare INCB001158 50 mg + pembrolizumab in participants with renal impairment with INCB001158 50 mg or 75 mg in participants with normal renal function. It was pre-specified to collect data for only the Part 1A INCB001158 50 mg, Part 1A: INCB001158 75 mg, and Part 1C: INCB001158 50 mg + Pembrolizumab arms. Participants in the INCB001158 100 mg and 150 mg arms did not contribute to the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 763 ng/mL | Geometric Coefficient of Variation 0.3 |
| Part 1A: INCB001158 75 mg | Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 1310 ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 1030 ng/mL | Geometric Coefficient of Variation 0.21 |
Secondary
Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
Cmax was defined as the maximum observed concentration of INCB001158.
Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
Population: PK Population. Only participants with available date were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 904 ng/mL | Geometric Coefficient of Variation 0.19 |
| Part 1A: INCB001158 50 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 955 ng/mL | Geometric Coefficient of Variation 0.38 |
| Part 1A: INCB001158 75 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 1860 ng/mL | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 75 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 1840 ng/mL | Geometric Coefficient of Variation 0.31 |
| Part 1A: INCB001158 100 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 1990 ng/mL | Geometric Coefficient of Variation 0.26 |
| Part 1A: INCB001158 100 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 2130 ng/mL | Geometric Coefficient of Variation 0.31 |
| Part 1A: INCB001158 150 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 3370 ng/mL | Geometric Coefficient of Variation 0.3 |
| Part 1A: INCB001158 150 mg | Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 4170 ng/mL | Geometric Coefficient of Variation 0.32 |
Comparison: Fed versus Fastedp-value: 0.770290% CI: [0.753, 1.483]ANOVA
Comparison: Fed versus Fastedp-value: 0.938490% CI: [0.762, 1.346]ANOVA
Comparison: Fed versus Fastedp-value: 0.673390% CI: [0.809, 1.415]ANOVA
Comparison: Fed versus Fastedp-value: 0.345690% CI: [0.83, 1.847]ANOVA
Secondary
Duration of Response (DOR)
DOR was defined as the number of months from the date of the first documentation of an objective response (CR or PR per RECIST v1.1) to the date of the first documentation of disease progression or death, whichever occurred first. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma will be evaluated using modified RECIST criteria. Kaplan-Meier (KM) product-limit estimates with a log-log transformation were used for 95% confidence interval calculation.
Time frame: Until disease progression/study discontinuation (up to approximately 5 years)
Population: REEP. Only participants with CR or PR were analyzed, and only cohorts with ≥5 objective responders were analyzed. Part 1c participants had renal impairment and received INCB001158 50 mg + pembrolizumab (half the RP2D of INCB001158). It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function. Two participants evaluable for PFS were not evaluable for response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1B: INCB001158 50 mg + Pembrolizumab | Duration of Response (DOR) | NA months |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Duration of Response (DOR) | NA months |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Duration of Response (DOR) | NA months |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Duration of Response (DOR) | 12.4 months |
Secondary
Objective Response Rate (ORR)
ORR was defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at any post-Baseline visits prior to first disease progression and alternative cancer therapy use. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma was evaluated using modified RECIST criteria. Confidence intervals were calculated based on the exact method for binomial distributions (Clopper Pearson). Two participants evaluable for PFS were not evaluable for response.
Time frame: Until disease progression/study discontinuation (up to approximately 5 years)
Population: Response Efficacy Evaluable Population (REEP): received ≥1 dose of INCB001158 or pembrolizumab, completed a Baseline scan, and met ≥1 protocol-defined criteria. Part 1c participants had renal impairment and received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Objective Response Rate (ORR) | 0.0 percentage of participants |
| Part 1A: INCB001158 75 mg | Objective Response Rate (ORR) | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Objective Response Rate (ORR) | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Objective Response Rate (ORR) | 0.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Objective Response Rate (ORR) | 10.0 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Objective Response Rate (ORR) | 7.7 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Objective Response Rate (ORR) | 0.0 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Objective Response Rate (ORR) | 1.4 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Objective Response Rate (ORR) | 11.0 percentage of participants |
Secondary
Percentage of Participants With the Indicated Best Overall Response (BOR)
BOR was evaluated per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Stable disease (SD): no change in target lesions to qualify for CR, PR, or progressive disease (PD). PD: progression of a target or non-target lesion or presence of a new lesion. Missing: participant had a missing BOR because there were no post-Baseline tumor assessments. Pleural mesothelioma was evaluated using modified RECIST criteria.
Time frame: Until disease progression/study discontinuation (up to approximately 5 years)
Population: REEP. Participants enrolled in Part 1c had renal impairment. These participants received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function. Two participants evaluable for PFS were not evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 33.3 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 0.0 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 0.0 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1A: INCB001158 50 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 66.7 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 0.0 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 85.7 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 0.0 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 0.0 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 14.3 percentage of participants |
| Part 1A: INCB001158 75 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 16.7 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 83.3 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 0.0 percentage of participants |
| Part 1A: INCB001158 100 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 33.3 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 66.7 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1A: INCB001158 150 mg | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 0.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 10.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 70.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 10.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 10.0 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 46.2 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 7.7 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 38.5 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 7.7 percentage of participants |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 0.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 0.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 80.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 0.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 20.0 percentage of participants |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 1.4 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 50.7 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 4.1 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 0.0 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 13.7 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 30.1 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Partial Response | 9.3 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Missing | 3.4 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Assessed | 0.0 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Not Evaluable | 4.2 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Complete Response | 1.7 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Progressive Disease | 44.9 percentage of participants |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Percentage of Participants With the Indicated Best Overall Response (BOR) | Stable Disease | 36.4 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS was defined as the length of time between the date of the first dose and the earlier of death or progressive disease as assessed by RECIST v1.1. Pleural mesothelioma was evaluated using modified RECIST criteria. Participants enrolled in Part 1c had renal impairment. These participants received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. In renally impaired participants, the 50 mg dose has comparable exposure to 100 mg in participants with normal renal function. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function.
Time frame: Until disease progression/study discontinuation (up to approximately 5 years)
Population: PFS Efficacy Evaluable Population (Full Analysis Set): all participants who received at least 1 dose of INCB001158 or pembrolizumab. One participant was to be treated with INCB001158 100 mg + pembrolizumab but actually received INCB001158 75 mg + pembrolizumab. For PFS analysis, this participant was analyzed in their planned treatment group (INCB001158 100 mg + pembrolizumab) rather than in the actual treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Progression-free Survival (PFS) | 1.8 months |
| Part 1A: INCB001158 75 mg | Progression-free Survival (PFS) | 1.8 months |
| Part 1A: INCB001158 100 mg | Progression-free Survival (PFS) | 1.8 months |
| Part 1A: INCB001158 150 mg | Progression-free Survival (PFS) | 2.1 months |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Progression-free Survival (PFS) | 2.1 months |
| Part 1B: INCB001158 75 mg + Pembrolizumab | Progression-free Survival (PFS) | 2.6 months |
| Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab | Progression-free Survival (PFS) | 2.1 months |
| Part 1C: INCB001158 50 mg + Pembrolizumab | Progression-free Survival (PFS) | 1.9 months |
| Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab | Progression-free Survival (PFS) | 3.0 months |
Secondary
Recommended Phase 2 Dose (RP2D) of INCB001158
The RP2D was determined by a traditional 3+3 dose-escalation design of single-agent INCB001158 in participants with advanced/metastatic solid tumors at doses of 50, 75, 100, or 150 mg.
Time frame: 12 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Recommended Phase 2 Dose (RP2D) of INCB001158 | 100 milligrams |
Secondary
RP2D of INCB001158 in Combination With Pembrolizumab
INCB001158 was dosed orally BID.
Time frame: 12 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: INCB001158 50 mg | RP2D of INCB001158 in Combination With Pembrolizumab | 100 milligrams |
Secondary
t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A
t1/2 was defined as the half-life of INCB001158.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A | 5.54 hours | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 75 mg | t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A | 5.22 hours | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 100 mg | t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A | 5.70 hours | Geometric Coefficient of Variation 0.4 |
| Part 1A: INCB001158 150 mg | t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A | 6.83 hours | Geometric Coefficient of Variation 0.28 |
Secondary
t1/2 of INCB001158 Following Single Escalating Doses for Part 1A
t1/2 was defined as the half-life of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | t1/2 of INCB001158 Following Single Escalating Doses for Part 1A | 5.33 hours | Geometric Coefficient of Variation 0.25 |
| Part 1A: INCB001158 75 mg | t1/2 of INCB001158 Following Single Escalating Doses for Part 1A | 5.21 hours | Geometric Coefficient of Variation 0.17 |
| Part 1A: INCB001158 100 mg | t1/2 of INCB001158 Following Single Escalating Doses for Part 1A | 5.70 hours | Geometric Coefficient of Variation 0.13 |
| Part 1A: INCB001158 150 mg | t1/2 of INCB001158 Following Single Escalating Doses for Part 1A | 5.65 hours | Geometric Coefficient of Variation 0.15 |
Secondary
Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A
tmax was defined as the time of the maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 2.0 hours |
| Part 1A: INCB001158 75 mg | Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 4.1 hours |
| Part 1A: INCB001158 100 mg | Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 4.0 hours |
| Part 1A: INCB001158 150 mg | Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A | 2.0 hours |
p-value: 0.0518Kruskal-Wallis
Secondary
Tmax of INCB001158 Following Single Escalating Doses for Part 1A
tmax was defined as the time of the maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 Following Single Escalating Doses for Part 1A | 3.9 hours |
| Part 1A: INCB001158 75 mg | Tmax of INCB001158 Following Single Escalating Doses for Part 1A | 2.0 hours |
| Part 1A: INCB001158 100 mg | Tmax of INCB001158 Following Single Escalating Doses for Part 1A | 4.0 hours |
| Part 1A: INCB001158 150 mg | Tmax of INCB001158 Following Single Escalating Doses for Part 1A | 6.0 hours |
p-value: 0.1496Kruskal-Wallis
Secondary
Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
tmax was defined as the time of the maximum observed concentration of INCB001158.
Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
Population: PK Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Capsule | 3.8 hours |
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation | Tablet | 3.8 hours |
Comparison: Tablet (test) versus Capsule (reference)p-value: 0.754Wilcoxon (Mann-Whitney)
Secondary
Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
tmax was defined as the time of the maximum observed concentration of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.
Population: PK Population. Analysis was conducted to compare INCB001158 50 mg + pembrolizumab in participants with renal impairment with INCB001158 50 mg or 75 mg in participants with normal renal function. It was pre-specified to collect data for only the Part 1A INCB001158 50 mg, Part 1A: INCB001158 75 mg, and Part 1C: INCB001158 50 mg + Pembrolizumab arms. Participants in the INCB001158 100 mg and 150 mg arms did not contribute to the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 3.9 hours |
| Part 1A: INCB001158 75 mg | Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 2.0 hours |
| Part 1B: INCB001158 50 mg + Pembrolizumab | Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A) | 5.9 hours |
Secondary
Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
tmax was defined as the time of the maximum observed concentration of INCB001158.
Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
Population: PK Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 2.0 hours |
| Part 1A: INCB001158 50 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 4.0 hours |
| Part 1A: INCB001158 75 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 4.0 hours |
| Part 1A: INCB001158 75 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 4.0 hours |
| Part 1A: INCB001158 100 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 4.0 hours |
| Part 1A: INCB001158 100 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 4.0 hours |
| Part 1A: INCB001158 150 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fasted | 2.0 hours |
| Part 1A: INCB001158 150 mg | Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food | Fed | 4.0 hours |
Comparison: Fed versus Fastedp-value: 0.0441Wilcoxon (Mann-Whitney)
Comparison: Fed versus Fastedp-value: 0.4092Wilcoxon (Mann-Whitney)
Comparison: Fed versus Fastedp-value: 0.7748Wilcoxon (Mann-Whitney)
Comparison: Fed versus Fastedp-value: 0.1948Wilcoxon (Mann-Whitney)
Secondary
Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A
Vz/F was defined as the apparent volume of distribution of INCB001158.
Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 48400 Liters | Geometric Coefficient of Variation 0.34 |
| Part 1A: INCB001158 75 mg | Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 34000 Liters | Geometric Coefficient of Variation 0.48 |
| Part 1A: INCB001158 100 mg | Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 45000 Liters | Geometric Coefficient of Variation 0.09 |
| Part 1A: INCB001158 150 mg | Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A | 49700 Liters | Geometric Coefficient of Variation 0.3 |
Secondary
Vz/F of INCB001158 Following Single Escalating Doses for Part 1A
Vz/F was defined as the apparent volume of distribution of INCB001158.
Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1A: INCB001158 50 mg | Vz/F of INCB001158 Following Single Escalating Doses for Part 1A | 46000 Liters | Geometric Coefficient of Variation 0.29 |
| Part 1A: INCB001158 75 mg | Vz/F of INCB001158 Following Single Escalating Doses for Part 1A | 40100 Liters | Geometric Coefficient of Variation 0.22 |
| Part 1A: INCB001158 100 mg | Vz/F of INCB001158 Following Single Escalating Doses for Part 1A | 51300 Liters | Geometric Coefficient of Variation 0.32 |
| Part 1A: INCB001158 150 mg | Vz/F of INCB001158 Following Single Escalating Doses for Part 1A | 50100 Liters | Geometric Coefficient of Variation 0.3 |