Solid Tumors
Conditions
Keywords
Solid tumor, lymphoma, leukemia, AML, myelodysplastic syndrome (MDS), multiple myeloma, myeloproliferative neoplasm (MPN), MDS/MPN, myelofibrosis (MF), pancreatic cancer, colorectal cancer, non-small cell lung cancer, prostate cancer, breast cancer, ovarian cancer, glioblastoma multiforme (GBM), NUT midline carcinoma, non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), double-hit, triple-hit, myc, bromodomain and extra-terminal (BET) inhibitor
Brief summary
The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies. Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.
Interventions
DRUGGemcitabine
Standard of Care (SOC) agents
DRUGPaclitaxel
Standard of Care (SOC) agents
DRUGRucaparib
Standard of Care (SOC) agents
DRUGAbiraterone
Standard of Care (SOC) agents
DRUGRuxolitinib
Standard of Care (SOC) agents
DRUGAzacitidine
Standard of Care (SOC) agents
DRUGINCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
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 relapsed or refractory advanced or metastatic malignancies: * Part 1: solid tumors or lymphomas, or hematologic malignancies * Part 2: histologically confirmed disease in specific tumor types * Part 3: advanced solid tumor or hematologic malignancy * Part 4: select advanced solid tumor or hematologic malignancy * For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy) * For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort. * Life expectancy \> 12 weeks, for MF subjects in Parts 3 and 4, life expectancy \> 24 weeks * Eastern Cooperative Oncology Group (ECOG) performance status * Parts 1 and 3: 0 or 1 * Parts 2 and 4: 0, 1, or 2 * Willingness to avoid pregnancy or fathering children
Exclusion criteria
* Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count * Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase. * Receipt of anticancer medications or investigational drugs within protocol-specified intervals * Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant * Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment * Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy * Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval * Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment * Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed * History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful * Type 1 diabetes or uncontrolled Type 2 diabetes * HbA1c of ≥ 8% (all subjects will have HbA1c test at screening) * Any sign of clinically significant bleeding * Coagulation panel within protocol-specified parameters
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE's). | From screening through at least 30 days after end of treatment, up to approximately 24 months | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months | Objective response rate is defined as the proportion of subjects who have an objective response using the applicable disease assessment criteria. ORR was proportion of participants with best overall response \[complete response (CR) or partial response (PR)\]. |
| Cmax: Maximum Observed Plasma Concentration of INCB057643. | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8 | Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state. |
| Tmax: Time to Maximum Plasma Concentration of INCB057643 | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8 | Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state |
| Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, for C1D1 and C1D8, and 24hrs post dose for C1D1 | An ex vivo assay (utilized in monotherapy only), Measuring Total c-Myc protein expressed from an exogenously added cell line (KMS12BM) to patient plasma, before and after administration of INCB057643. |
| AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8 | Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fasted state |
| Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643. | C2D1 | Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state. |
| Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643 | C2D1 | Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state |
| AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 | Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB057643 administered as monotherapy in fasted state |
Countries
Belgium, France, United States
Participant flow
Recruitment details
A total of 137 subjects enrolled at 19 different sites in USA.
Pre-assignment details
Subjects were assigned to either dose escalation/dose-expansion study of INCB057643 as monotherapy or in combination with SOC agents in subjects with relapsing or refractory malignancies.
Participants by arm
| Arm | Count |
|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma | 4 |
| Part1/Treatment Group A : 12mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma | 5 |
| Part1/Treatment Group A : 16mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma | 8 |
| Part1/Treatment Group B : 8mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF | 7 |
| Part1/Treatment Group B : 12mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | 5 |
| Part1/Treatment Group C : 8mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | 1 |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | 86 |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | 5 |
| Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | 1 |
| Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | 2 |
| Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | 4 |
| Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | 3 |
| Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | 1 |
| Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome | 2 |
| Enrolled But Not Dosed 3 participants enrolled in the study and discontinued the study before study drug is administered | 3 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 4 | 5 | 5 | 3 | 1 | 61 | 3 | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 2 | 1 | 1 | 0 | 12 | 2 | 1 | 1 | 3 | 2 | 1 | 1 | 2 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 1 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Enrolled But Not Dosed | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 10.21 | 60.2 Years STANDARD_DEVIATION 12.26 | 60.5 Years STANDARD_DEVIATION 11.44 | 68.9 Years STANDARD_DEVIATION 5.81 | 75.8 Years STANDARD_DEVIATION 7.33 | 70.0 Years | 60.6 Years STANDARD_DEVIATION 13.8 | 72.6 Years STANDARD_DEVIATION 10.92 | 72.0 Years STANDARD_DEVIATION 0 | 56.0 Years STANDARD_DEVIATION 12.73 | 66.0 Years STANDARD_DEVIATION 6.16 | 67.7 Years STANDARD_DEVIATION 4.04 | 75.0 Years STANDARD_DEVIATION 0 | 76.5 Years STANDARD_DEVIATION 2.12 | 66.0 Years STANDARD_DEVIATION 6.24 | 63.0 Years STANDARD_DEVIATION 12.8 |
| Race/Ethnicity, Customized American-Indian/Alaska Native | 0 Participants | 0 Participants | 0 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 | 1 Participants |
| Race/Ethnicity, Customized Asian | 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 | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 10 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 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 | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 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 | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized White/Caucasian | 3 Participants | 3 Participants | 5 Participants | 6 Participants | 4 Participants | 0 Participants | 71 Participants | 5 Participants | 0 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 111 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 5 Participants | 3 Participants | 1 Participants | 0 Participants | 48 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 68 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 1 Participants | 38 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 69 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 | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 4 / 5 | 5 / 8 | 6 / 7 | 4 / 5 | 1 / 1 | 68 / 86 | 3 / 5 | 0 / 1 | 1 / 2 | 1 / 4 | 1 / 3 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 7 / 8 | 7 / 7 | 5 / 5 | 0 / 1 | 82 / 86 | 5 / 5 | 1 / 1 | 2 / 2 | 4 / 4 | 3 / 3 | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 2 / 4 | 1 / 5 | 4 / 8 | 5 / 7 | 4 / 5 | 1 / 1 | 32 / 86 | 4 / 5 | 0 / 1 | 0 / 2 | 0 / 4 | 1 / 3 | 1 / 1 | 0 / 2 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAE's).
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Time frame: From screening through at least 30 days after end of treatment, up to approximately 24 months
Population: All participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 4 Participants |
| Part1/Treatment Group A : 12mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 5 Participants |
| Part1/Treatment Group A : 16mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 8 Participants |
| Part1/Treatment Group B : 8mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 7 Participants |
| Part1/Treatment Group B : 12mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 5 Participants |
| Part1/Treatment Group C : 8mg QD INCB057643 | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 1 Participants |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 86 Participants |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 5 Participants |
| Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 1 Participants |
| Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 2 Participants |
| Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 4 Participants |
| Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 3 Participants |
| Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 1 Participants |
| Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Number of Participants With Treatment Emergent Adverse Events (TEAE's). | 2 Participants |
Secondary
AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy
Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fed state.
Time frame: C2D1
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy | 2980 h*nM | Standard Deviation 31.5 |
Secondary
AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy
Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fasted state
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy | 1940 h*nM | Standard Deviation 45.1 |
| Part1/Treatment Group A : 12mg QD INCB057643 | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy | 2740 h*nM | Standard Deviation 43.2 |
| Part1/Treatment Group A : 16mg QD INCB057643 | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy | 3610 h*nM | Standard Deviation 71.9 |
Secondary
AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643
Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB057643 administered as monotherapy in fasted state
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 | 2090 h*nM | Standard Deviation 50.1 |
| Part1/Treatment Group A : 12mg QD INCB057643 | AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 | 2550 h*nM | Standard Deviation 39.5 |
| Part1/Treatment Group A : 16mg QD INCB057643 | AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 | 3210 h*nM | Standard Deviation 34.3 |
Secondary
Cmax: Maximum Observed Plasma Concentration of INCB057643.
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D1 | 201 nM | Standard Deviation 83.6 |
| Part1/Treatment Group A : 8mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D8 | 210 nM | Standard Deviation 93.2 |
| Part1/Treatment Group A : 12mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D1 | 266 nM | Standard Deviation 94.7 |
| Part1/Treatment Group A : 12mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D8 | 293 nM | Standard Deviation 113 |
| Part1/Treatment Group A : 16mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D1 | 343 nM | Standard Deviation 93.2 |
| Part1/Treatment Group A : 16mg QD INCB057643 | Cmax: Maximum Observed Plasma Concentration of INCB057643. | C1D8 | 340 nM | Standard Deviation 165 |
Secondary
Objective Response Rate (ORR) With INCB057643 in Solid Tumors
Objective response rate is defined as the proportion of subjects who have an objective response using the applicable disease assessment criteria. ORR was proportion of participants with best overall response \[complete response (CR) or partial response (PR)\].
Time frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months
Population: The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Lymphoma | 1 Participants |
| Part1/Treatment Group A : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part1/Treatment Group A : 12mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part1/Treatment Group A : 12mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Lymphoma | 0 Participants |
| Part1/Treatment Group A : 16mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part1/Treatment Group A : 16mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Lymphoma | 1 Participants |
| Part1/Treatment Group B : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | AML | 0 Participants |
| Part1/Treatment Group B : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelodysplastic Syndrome | 0 Participants |
| Part1/Treatment Group B : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelofibrosis | 0 Participants |
| Part1/Treatment Group B : 12mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | AML | 0 Participants |
| Part1/Treatment Group B : 12mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelodysplastic Syndrome | 0 Participants |
| Part1/Treatment Group C : 8mg QD INCB057643 | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Multiple Myeloma | 0 Participants |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Lymphoma | 2 Participants |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Glioblastoma | 0 Participants |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | AML | 1 Participants |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelodysplastic Syndrome | 0 Participants |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelofibrosis | 0 Participants |
| Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 1 Participants |
| Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Solid Tumors | 0 Participants |
| Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | Myelofibrosis | 0 Participants |
| Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Objective Response Rate (ORR) With INCB057643 in Solid Tumors | AML | 0 Participants |
Secondary
Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643.
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state.
Time frame: C2D1
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643. | 220 nM | Standard Deviation 32 |
Secondary
Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state
Time frame: C2D1
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643 | 6.00 hours |
Secondary
Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay
An ex vivo assay (utilized in monotherapy only), Measuring Total c-Myc protein expressed from an exogenously added cell line (KMS12BM) to patient plasma, before and after administration of INCB057643.
Time frame: PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, for C1D1 and C1D8, and 24hrs post dose for C1D1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D1 | 24 %Inhibition of Total c-Myc | Standard Error 199.5 |
| Part1/Treatment Group A : 8mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D8 | 30 %Inhibition of Total c-Myc | Standard Error 42.59 |
| Part1/Treatment Group A : 12mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D1 | 28 %Inhibition of Total c-Myc | Standard Error 200.1 |
| Part1/Treatment Group A : 12mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D8 | 43.4 %Inhibition of Total c-Myc | Standard Error 52.7 |
| Part1/Treatment Group A : 16mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D1 | 54 %Inhibition of Total c-Myc | Standard Error 236.3 |
| Part1/Treatment Group A : 16mg QD INCB057643 | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay | C1D8 | 65 %Inhibition of Total c-Myc | Standard Error 55.21 |
Secondary
Tmax: Time to Maximum Plasma Concentration of INCB057643
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Population: PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D1 | 2.00 hours |
| Part1/Treatment Group A : 8mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D8 | 1.00 hours |
| Part1/Treatment Group A : 12mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D1 | 2 hours |
| Part1/Treatment Group A : 12mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D8 | 2 hours |
| Part1/Treatment Group A : 16mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D1 | 2.00 hours |
| Part1/Treatment Group A : 16mg QD INCB057643 | Tmax: Time to Maximum Plasma Concentration of INCB057643 | C1D8 | 2.00 hours |