Trial Outcomes & Findings for Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies (NCT NCT02711137)

Last Updated: 2025-10-21

Results Overview

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

137 participants

Primary outcome timeframe

From screening through at least 30 days after end of treatment, up to approximately 24 months

Results posted on

2025-10-21

Participant Flow

A total of 137 subjects enrolled at 19 different sites in USA.

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.

Participant milestones

Participant milestones
Measure	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	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	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	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	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.	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	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.	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.	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	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.	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.	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	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.	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	Enrolled But Not Dosed 3 participants enrolled in the study and discontinued the study before study drug is administered
Overall Study STARTED	4	5	8	7	5	1	86	5	1	2	4	3	1	2	3
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	4	5	8	7	5	1	86	5	1	2	4	3	1	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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	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	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	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.	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	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.	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.	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	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.	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.	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	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.	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	Enrolled But Not Dosed 3 participants enrolled in the study and discontinued the study before study drug is administered
Overall Study Death	1	4	5	5	3	1	61	3	0	1	1	1	0	0	0
Overall Study Study Terminated by Sponsor	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Overall Study Physician Decision	1	0	2	1	1	0	12	2	1	1	3	2	1	1	2
Overall Study Other	0	1	0	0	0	0	3	0	0	0	0	0	0	0	1
Overall Study Withdrawal by Subject	1	0	0	1	1	0	7	0	0	0	0	0	0	1	0
Overall Study Lost to Follow-up	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0

Baseline Characteristics

Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part1/Treatment Group A : 8mg QD INCB057643 n=4 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 12mg QD INCB057643 n=5 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 16mg QD INCB057643 n=8 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group B : 8mg QD INCB057643 n=7 Participants 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	Part1/Treatment Group B : 12mg QD INCB057643 n=5 Participants 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.	Part1/Treatment Group C : 8mg QD INCB057643 n=1 Participants 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	Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort n=86 Participants 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.	Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort n=5 Participants 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.	Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg n=1 Participants 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	Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg n=2 Participants 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.	Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg n=4 Participants 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.	Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni n=3 Participants 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	Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg n=1 Participants 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.	Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg n=2 Participants 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	Enrolled But Not Dosed n=3 Participants 3 participants enrolled in the study and discontinued the study before study drug is administered	Total n=137 Participants Total of all reporting groups
Age, Continuous	64.3 Years STANDARD_DEVIATION 10.21 • n=5 Participants	60.2 Years STANDARD_DEVIATION 12.26 • n=7 Participants	60.5 Years STANDARD_DEVIATION 11.44 • n=5 Participants	68.9 Years STANDARD_DEVIATION 5.81 • n=4 Participants	75.8 Years STANDARD_DEVIATION 7.33 • n=21 Participants	70.0 Years STANDARD_DEVIATION NA • n=8 Participants	60.6 Years STANDARD_DEVIATION 13.80 • n=8 Participants	72.6 Years STANDARD_DEVIATION 10.92 • n=24 Participants	72.0 Years STANDARD_DEVIATION 0 • n=42 Participants	56.0 Years STANDARD_DEVIATION 12.73 • n=42 Participants	66.0 Years STANDARD_DEVIATION 6.16 • n=42 Participants	67.7 Years STANDARD_DEVIATION 4.04 • n=42 Participants	75.0 Years STANDARD_DEVIATION 0 • n=36 Participants	76.5 Years STANDARD_DEVIATION 2.12 • n=36 Participants	66.0 Years STANDARD_DEVIATION 6.24 • n=24 Participants	63.0 Years STANDARD_DEVIATION 12.80 • n=135 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	48 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	4 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	1 Participants n=24 Participants	68 Participants n=135 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	1 Participants n=8 Participants	38 Participants n=8 Participants	5 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants	1 Participants n=36 Participants	2 Participants n=36 Participants	2 Participants n=24 Participants	69 Participants n=135 Participants
Race/Ethnicity, Customized White/Caucasian	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	71 Participants n=8 Participants	5 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	4 Participants n=42 Participants	3 Participants n=42 Participants	1 Participants n=36 Participants	2 Participants n=36 Participants	3 Participants n=24 Participants	111 Participants n=135 Participants
Race/Ethnicity, Customized Black/African American	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	10 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	16 Participants n=135 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants
Race/Ethnicity, Customized American-Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	1 Participants n=135 Participants
Race/Ethnicity, Customized Native Hawaiian/Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	1 Participants n=135 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	2 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	6 Participants n=135 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	1 Participants n=135 Participants

PRIMARY outcome

Timeframe: 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.

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Outcome measures

Outcome measures
Measure	Part1/Treatment Group A : 8mg QD INCB057643 n=4 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 12mg QD INCB057643 n=5 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 16mg QD INCB057643 n=8 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group B : 8mg QD INCB057643 n=7 Participants 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	Part1/Treatment Group B : 12mg QD INCB057643 n=5 Participants 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.	Part1/Treatment Group C : 8mg QD INCB057643 n=1 Participants 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	Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort n=86 Participants 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.	Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort n=5 Participants 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.	Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg n=1 Participants 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	Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg n=2 Participants 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.	Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg n=4 Participants 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.	Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni n=3 Participants 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	Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg n=1 Participants 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.	Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg n=2 Participants 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
Number of Participants With Treatment Emergent Adverse Events (TEAE's).	4 Participants	5 Participants	8 Participants	7 Participants	5 Participants	1 Participants	86 Participants	5 Participants	1 Participants	2 Participants	4 Participants	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part1/Treatment Group A : 8mg QD INCB057643 n=11 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 12mg QD INCB057643 n=51 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	Part1/Treatment Group A : 16mg QD INCB057643 n=7 Participants Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma	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	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.	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	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.	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.	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	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.	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.	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	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.	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
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	28 %Inhibition of Total c-Myc Standard Error 200.1	54 %Inhibition of Total c-Myc Standard Error 236.3	—	—	—	—	—	—	—	—	—	—	—
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	43.4 %Inhibition of Total c-Myc Standard Error 52.7	65 %Inhibition of Total c-Myc Standard Error 55.21	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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 \[complete response (CR) or partial response (PR)\].