Biliary Tract Cancer (BTC), Colorectal Cancer (CRC), Endometrial Cancer, Gastroesophageal Cancer (GC), Ovarian Cancer, Solid Tumors
Conditions
Keywords
INCB001158, arginase inhibitor, oxaliplatin, leucovorin, 5 fluorouracil, gemcitabine, cisplatin, paclitaxel, solid tumors, colorectal cancer, biliary tract cancer, gastroesophageal cancer, endometrial cancer, ovarian cancer
Brief summary
The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.
Interventions
DRUGINCB001158
Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.
DRUGOxaliplatin
Oxaliplatin administered intravenously at the protocol-defined dose and schedule.
DRUGLeucovorin
Leucovorin at the protocol-defined dose and regimen.
DRUG5-Fluorouracil
5-Fluorouracil at the protocol-defined dose and regimen.
DRUGGemcitabine
Gemcitabine at the protocol-defined dose and regimen.
DRUGCisplatin
Cisplatin at the protocol-defined dose and regimen.
DRUGPaclitaxel
Paclitaxel at the protocol-defined dose and regimen.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors. * Presence of measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. * Resolution of treatment-related toxicities. * Adequate hepatic, renal, cardiac, and hematologic function. * Additional cohort-specific criteria may apply.
Exclusion criteria
* Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose. * Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug. * Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment. * Has received prior approved radiotherapy within 14 days of study therapy. * Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Has an active infection requiring systemic therapy. * Has known active CNS metastases and/or carcinomatous meningitis. * Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 1385 days | 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 drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. |
| Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | up to Day 28 | A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. |
| Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen | up to Day 580 | The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2. |
| Phase 2: Objective Response Rate (ORR) | up to 1385 days | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (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 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. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection | Cmin was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward. |
| Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection | Cmax was defined as the maximum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward. |
| Phase 1: ORR | up to 580 days | ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, as determined by investigator assessment of radiographic disease as 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. |
| AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection | AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward. |
| Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection | tlast was defined as the time of the last sample collected from which a concentration was measured. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward. |
| Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection | tmax was defined as the time to the maximum concentration. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward. |
| Phases 1 and 2: Duration of Response | up to 368 days | DOR was defined as the time from initial objective response (CR or PR) (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if it occurred sooner than disease progression. 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. PD: progression of a target or non-target lesion or presence of a new lesion. |
| Phases 1 and 2: Disease Control Rate | up to 1385 days | DCR was defined as the percentage of participants with an overall response of CR, PR, or stable disease (SD), as determined by investigator assessment of radiographic disease as per RECIST v1.1, for at least 8 weeks. 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. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. |
| Phases 1 and 2: Progression-free Survival | up to 1385 days | According to RECIST 1.1, PFS was defined as the length of time from the date of the first dose study of drug until the earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death due to any cause, if it occurred sooner than progression. |
Countries
Belgium, United Kingdom, United States
Participant flow
Pre-assignment details
This study was conducted at 11 study centers in the United States, the United Kingdom, and Belgium.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: INCB001158 50 mg + mFOLFOX6 In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 milligrams (mg) twice daily (BID) starting on Day 1 of each 28-day cycle. Participants also received intravenous modified FOLFOX6 (mFOLFOX6: oxaliplatin 85 mg/meters squared \[m\^2\], leucovorin 400 mg/m\^2, and 5-fluorouracil 400 mg/m\^2 \[bolus\] and 2400 mg/m\^2 \[continuous infusion\]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158. | 8 |
| Phase 1: INCB001158 75 mg + mFOLFOX6 In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2, and 5-fluorouracil 400 mg/m\^2 \[bolus\] and 2400 mg/m\^2 \[continuous infusion\]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158. | 6 |
| Phase 1: INCB001158 100 mg + mFOLFOX6 In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2, and 5-fluorouracil 400 mg/m\^2 \[bolus\] and 2400 mg/m\^2 \[continuous infusion\]) on Day 1 and Day 15 of each 28-day cyce after administration of INCB001158. | 6 |
| Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m\^2 and intravenous cisplatin 30 mg/m\^2 on Day 1 and Day 8 of each 28-day cycle. | 7 |
| Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m\^2 and intravenous cisplatin 30 mg/m\^2 on Day 1 and Day 8 of each 28-day cycle. | 4 |
| Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m\^2 and intravenous cisplatin 30 mg/m\^2 on Day 1 and Day 8 of each 28-day cycle. | 4 |
| Phase 1: INCB001158 50 mg + Paclitaxel In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 50 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 7 |
| Phase 1: INCB001158 75 mg + Paclitaxel In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 75 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 5 |
| Phase 1: INCB001158 100 mg + Paclitaxel In Phase 1, participants with advanced or metastatic solid tumors received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 7 |
| Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1) In Phase 2, participants with microsatellite-stable-colorectal cancer (MSS-CRC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2, and 5-fluorouracil 400 mg/m\^2 \[bolus\] and 2400 mg/m\^2 \[continuous infusion\]) on Day 1 and Day 15 of each 28-day cycle after administration of INCB001158. | 8 |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: BTC (Cohort B1) In Phase 2, participants with biliary tract cancer (BTC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 1000 mg/m\^2 and intravenous cisplatin 25 mg/m\^2 on Day 1 and 8 of each 28-day cycle. | 33 |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: OC (Cohort B2) In Phase 2, participants with ovarian cancer (OC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous gemcitabine 750 mg/m\^2 and intravenous cisplatin 30 mg/m\^2 on Day 1 and 8 of each 28-day cycle. | 9 |
| Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1) In Phase 2, participants with gastroesophageal cancer (GC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 11 |
| Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2) In Phase 2, participants with endometrial cancer (EC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 10 |
| Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3) In Phase 2, participants with ovarian cancer (OC) received oral INCB001158 100 mg BID starting on Day 1 of each 28-day cycle. Participants also received intravenous paclitaxel 80 mg/m\^2 on Day 1, Day 8, and Day 15 of each 28-day cycle. | 24 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 | Captured as Other in Database | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Death | 4 | 2 | 5 | 4 | 3 | 4 | 5 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Progressive Disease | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Study Terminated by Sponsor | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 | Withdrawal by Subject | 2 | 1 | 1 | 2 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 20 | 6 | 7 | 6 | 17 |
| Phase 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Phase 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Phase 2 | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 0 | 1 |
| Phase 2 | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 2 | 1 | 4 | 4 |
| Phase 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3) | Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2) | Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1) | Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: OC (Cohort B2) | Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: BTC (Cohort B1) | Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1) | Phase 1: INCB001158 100 mg + Paclitaxel | Phase 1: INCB001158 75 mg + Paclitaxel | Phase 1: INCB001158 50 mg + Paclitaxel | Phase 1: INCB001158 100 mg + Gemcitabine + Cisplatin | Phase 1: INCB001158 75 mg + Gemcitabine + Cisplatin | Phase 1: INCB001158 50 mg + Gemcitabine + Cisplatin | Phase 1: INCB001158 100 mg + mFOLFOX6 | Phase 1: INCB001158 75 mg + mFOLFOX6 | Phase 1: INCB001158 50 mg + mFOLFOX6 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.93 years STANDARD_DEVIATION 11.66 | 60.6 years STANDARD_DEVIATION 9.04 | 62.3 years STANDARD_DEVIATION 9.29 | 58.8 years STANDARD_DEVIATION 11.9 | 65.3 years STANDARD_DEVIATION 8.87 | 59.3 years STANDARD_DEVIATION 12.74 | 62.8 years STANDARD_DEVIATION 11.26 | 61.4 years STANDARD_DEVIATION 6.95 | 47.4 years STANDARD_DEVIATION 10.29 | 62.0 years STANDARD_DEVIATION 14.57 | 54.0 years STANDARD_DEVIATION 15.64 | 64.5 years STANDARD_DEVIATION 16.82 | 54.0 years STANDARD_DEVIATION 18.93 | 65.2 years STANDARD_DEVIATION 7.99 | 60.3 years STANDARD_DEVIATION 9.93 | 56.4 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 136 Participants | 23 Participants | 10 Participants | 11 Participants | 7 Participants | 29 Participants | 7 Participants | 7 Participants | 5 Participants | 7 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized American-Indian/Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African-American | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/Carribean | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Captured as Hispanic/Latino in Database | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized East Indian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Provided/Specified | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 129 Participants | 23 Participants | 8 Participants | 8 Participants | 8 Participants | 31 Participants | 7 Participants | 5 Participants | 5 Participants | 7 Participants | 4 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Female | 103 Participants | 24 Participants | 10 Participants | 4 Participants | 9 Participants | 21 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 46 Participants | 0 Participants | 0 Participants | 7 Participants | 0 Participants | 12 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 5 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 | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 8 | 2 / 6 | 11 / 14 | 4 / 7 | 3 / 4 | 30 / 46 | 5 / 7 | 4 / 5 | 36 / 52 | 99 / 149 |
| other Total, other adverse events | 8 / 8 | 6 / 6 | 13 / 14 | 7 / 7 | 4 / 4 | 45 / 46 | 7 / 7 | 5 / 5 | 50 / 52 | 145 / 149 |
| serious Total, serious adverse events | 6 / 8 | 1 / 6 | 7 / 14 | 3 / 7 | 1 / 4 | 30 / 46 | 4 / 7 | 4 / 5 | 27 / 52 | 83 / 149 |
Outcome results
Primary
Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)
A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.
Time frame: up to Day 28
Population: Phase 1 DLT Evaluable Population: all participants enrolled in Phase 1 who had been treated with the assigned dose level of INCB001158 and who had received at least 32 of the 42 doses prescribed for a 21-day cycle regimen or at least 42 of the 56 doses prescribed for a 28-day cycle regimen (both representing ≥ 75% of the dose planned) or who had experienced a DLT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 1 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel | Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT) | 0 Participants |
Primary
Phase 2: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (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 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. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.
Time frame: up to 1385 days
Population: Phase 2 Response Evaluable Population: all participants who had received ≥1 dose of study treatment (INCB001158, mFOLFOX6, gemcitabine/cisplatin, or paclitaxel), completed a Baseline scan, and met ≥1 of the following criteria: (a) had ≥1 post-Baseline scan; (b) was in the study for a minimum of 63 days (8 weeks + 1 week window) of follow-up; (c) discontinued from study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phase 2: Objective Response Rate (ORR) | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phase 2: Objective Response Rate (ORR) | 24.2 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phase 2: Objective Response Rate (ORR) | 22.2 percentage of participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phase 2: Objective Response Rate (ORR) | 9.1 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phase 2: Objective Response Rate (ORR) | 30.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phase 2: Objective Response Rate (ORR) | 16.7 percentage of participants |
Primary
Phases 1 and 2: 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 drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time frame: up to 1385 days
Population: Full Analysis Set (FAS): all participants enrolled in the study who received at least 1 dose of INCB001158, mFOLFOX6, gemcitabine/cisplatin, or paclitaxel. As pre-defined in the Statistical Analysis Plan, data analysis was conducted based on treatment group and dose level, regardless of study phase, because the safety profile was expected to be generally uniform across tumor types.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 8 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 13 Participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 46 Participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 5 Participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel | Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 51 Participants |
Primary
Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen
The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.
Time frame: up to Day 580
Population: DLT Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen | 100 milligrams |
Secondary
AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration
AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.
Time frame: Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Population: Phase 2 PK Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 6910 hours x ng/mL | Geometric Coefficient of Variation 17.6 |
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 11000 hours x ng/mL | Geometric Coefficient of Variation 21.1 |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7240 hours x ng/mL | Geometric Coefficient of Variation 32.9 |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 10600 hours x ng/mL | Geometric Coefficient of Variation 55.3 |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 10600 hours x ng/mL | Geometric Coefficient of Variation 18.9 |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 12200 hours x ng/mL | Geometric Coefficient of Variation 34.4 |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 4680 hours x ng/mL | Geometric Coefficient of Variation 134 |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 10000 hours x ng/mL | Geometric Coefficient of Variation 18.4 |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 9290 hours x ng/mL | Geometric Coefficient of Variation 33.2 |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 14400 hours x ng/mL | Geometric Coefficient of Variation 13.7 |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 8840 hours x ng/mL | Geometric Coefficient of Variation 24.7 |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 12800 hours x ng/mL | Geometric Coefficient of Variation 30.3 |
Secondary
Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration
Cmax was defined as the maximum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.
Time frame: Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Population: Phase 2 PK Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 1290 ng/mL | Geometric Coefficient of Variation 16.4 |
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 1960 ng/mL | Geometric Coefficient of Variation 12.6 |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 1350 ng/mL | Geometric Coefficient of Variation 35.2 |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 1860 ng/mL | Geometric Coefficient of Variation 46.7 |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 2160 ng/mL | Geometric Coefficient of Variation 22.3 |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 2250 ng/mL | Geometric Coefficient of Variation 26.4 |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 1100 ng/mL | Geometric Coefficient of Variation 68 |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 1600 ng/mL | Geometric Coefficient of Variation 22 |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 1760 ng/mL | Geometric Coefficient of Variation 17.2 |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 2390 ng/mL | Geometric Coefficient of Variation 11.4 |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 1640 ng/mL | Geometric Coefficient of Variation 23.2 |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 2100 ng/mL | Geometric Coefficient of Variation 24.6 |
Secondary
Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration
Cmin was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.
Time frame: Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection
Population: Phase 2 Pharmacokinetic (PK) Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 747 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.7 |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 407 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 407 |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 268 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 888 |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 542 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 102 |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 1020 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.2 |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration | 633 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 131 |
Secondary
Phase 1: ORR
ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, as determined by investigator assessment of radiographic disease as 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.
Time frame: up to 580 days
Population: Phase 1 Response Evaluable Population: all participants who had received ≥1 dose of study treatment (INCB001158, mFOLFOX6, gemcitabine/cisplatin, or paclitaxel), completed a Baseline scan, and met ≥1 of the following criteria: (a) had ≥1 post-Baseline scan; (b) was in the study for a minimum of 63 days (8 weeks + 1 week window) of follow-up; (c) discontinued from study treatment. Analysis was conducted by dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phase 1: ORR | 12.5 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phase 1: ORR | 25.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel | Phase 1: ORR | 14.3 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel | Phase 1: ORR | 28.6 percentage of participants |
Secondary
Phases 1 and 2: Disease Control Rate
DCR was defined as the percentage of participants with an overall response of CR, PR, or stable disease (SD), as determined by investigator assessment of radiographic disease as per RECIST v1.1, for at least 8 weeks. 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. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.
Time frame: up to 1385 days
Population: Response Evaluable Population. Data analysis was conducted based on study phase. Additionally, analysis was conducted by dose in Phase 1 and by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phases 1 and 2: Disease Control Rate | 62.5 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phases 1 and 2: Disease Control Rate | 83.3 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phases 1 and 2: Disease Control Rate | 16.7 percentage of participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Disease Control Rate | 57.1 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Disease Control Rate | 75.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Disease Control Rate | 100.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel | Phases 1 and 2: Disease Control Rate | 42.9 percentage of participants |
| Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel | Phases 1 and 2: Disease Control Rate | 60.0 percentage of participants |
| Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel | Phases 1 and 2: Disease Control Rate | 85.7 percentage of participants |
| Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1) | Phases 1 and 2: Disease Control Rate | 100.0 percentage of participants |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: BTC (Cohort B1) | Phases 1 and 2: Disease Control Rate | 66.7 percentage of participants |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: OC (Cohort B2) | Phases 1 and 2: Disease Control Rate | 88.9 percentage of participants |
| Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1) | Phases 1 and 2: Disease Control Rate | 54.5 percentage of participants |
| Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2) | Phases 1 and 2: Disease Control Rate | 80.0 percentage of participants |
| Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3) | Phases 1 and 2: Disease Control Rate | 66.7 percentage of participants |
Secondary
Phases 1 and 2: Duration of Response
DOR was defined as the time from initial objective response (CR or PR) (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if it occurred sooner than disease progression. 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. PD: progression of a target or non-target lesion or presence of a new lesion.
Time frame: up to 368 days
Population: Response Evaluable Population. Analysis was conducted based on study phase. Analysis was conducted by dose in Phase 1 and by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates. Analysis was conducted in cohorts with \>5 objective responders; the Kaplan Meier estimation method on a sample size of \<5 responders is not valid. The confidence interval was calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: BTC (Cohort B1) | Phases 1 and 2: Duration of Response | 5.8 months |
Secondary
Phases 1 and 2: Progression-free Survival
According to RECIST 1.1, PFS was defined as the length of time from the date of the first dose study of drug until the earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death due to any cause, if it occurred sooner than progression.
Time frame: up to 1385 days
Population: FAS. Data analysis was conducted based on study phase. Additionally, analysis was conducted by dose in Phase 1 and by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates. Median survival time was estimated using the Kaplan-Meier method. CI for median survival time was calculated using the method of Brookmeyer and Crowley.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Phases 1 and 2: Progression-free Survival | 3.7 months |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Phases 1 and 2: Progression-free Survival | 6.6 months |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Phases 1 and 2: Progression-free Survival | 1.7 months |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Progression-free Survival | 3.9 months |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Progression-free Survival | 5.3 months |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Phases 1 and 2: Progression-free Survival | 6.4 months |
| Phase 1 and Phase 2: INCB001158 50 mg + Paclitaxel | Phases 1 and 2: Progression-free Survival | 3.9 months |
| Phase 1 and Phase 2: INCB001158 75 mg + Paclitaxel | Phases 1 and 2: Progression-free Survival | 3.7 months |
| Phase 1 and Phase 2: INCB001158 100 mg + Paclitaxel | Phases 1 and 2: Progression-free Survival | 11.8 months |
| Phase 2: INCB001158 100 mg + mFOLFOX6: MSS-CRC (Cohort A1) | Phases 1 and 2: Progression-free Survival | 3.7 months |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: BTC (Cohort B1) | Phases 1 and 2: Progression-free Survival | 8.5 months |
| Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin: OC (Cohort B2) | Phases 1 and 2: Progression-free Survival | 7.8 months |
| Phase 2: INCB001158 100 mg + Paclitaxel: GC (Cohort C1) | Phases 1 and 2: Progression-free Survival | 3.5 months |
| Phase 2: INCB001158 100 mg + Paclitaxel: EC (Cohort C2) | Phases 1 and 2: Progression-free Survival | 7.1 months |
| Phase 2: INCB001158 100 mg + Paclitaxel: OC (Cohort C3) | Phases 1 and 2: Progression-free Survival | 3.7 months |
Secondary
Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration
tlast was defined as the time of the last sample collected from which a concentration was measured. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.
Time frame: Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Population: Phase 2 PK Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.50 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.53 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.58 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.73 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.60 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.53 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.50 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.57 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.53 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.55 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 7.58 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 7.65 hours |
Secondary
Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration
tmax was defined as the time to the maximum concentration. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.
Time frame: Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Population: Phase 2 PK Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 4.13 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 4.00 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 4.07 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 4.00 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 4.08 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + mFOLFOX6 | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 4.06 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 5.05 hours |
| Phase 1 and Phase 2: INCB001158 50 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 4.13 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 4.09 hours |
| Phase 1 and Phase 2: INCB001158 75 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 3.85 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 1 Day 1 | 3.97 hours |
| Phase 1 and Phase 2: INCB001158 100 mg + Gemcitabine + Cisplatin | Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration | Cycle 2 Day 1 | 3.95 hours |