Solid TumorsPhase 1/2NCT02711137
Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
A Phase 1/2 study testing INCB057643, Gemcitabine and Paclitaxel in people with Solid Tumors, run by Incyte Corporation at 18 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- INCB057643, Gemcitabine and Paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 18 sitesin 3 countries
- Study dates
- 18 May 2016to 13 Feb 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
18 sites in 3 countries.
18 sites in 3 countries
United States16 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Alabama
Birmingham, Alabama, 35294-3300
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Sarah Cannon Research Institute at Health One
Denver, Colorado, 80218
Oncology Consultants, P.A.
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
University of California
La Jolla, California, 92093
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Yale University
New Haven, Connecticut, 06510
Hematology - Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, 34952
University of Rochester, Wilmot Cancer Center
Rochester, New York, 14642
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Washington University
St Louis, Missouri, 63110
MultiCare Institute for Research and Innovation
Tacoma, Washington, 98405
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
Belgium1 site
Institut Jules Bordet, Clinical Trial Conduct Unit
Brussels, B-1000
About this study
Official title: A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
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.
- Conditions
- Solid Tumors
- Being tested
- INCB057643, Gemcitabine, Paclitaxel, Rucaparib, Abiraterone
- 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
- Medical subject headings
- Lymphoma, Leukemia, Myelodysplastic Syndromes, Multiple Myeloma, Myeloproliferative Disorders, Primary Myelofibrosis, Pancreatic Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INCB057643Drug
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).
GemcitabineDrug
Standard of Care (SOC) agents
PaclitaxelDrug
Standard of Care (SOC) agents
RucaparibDrug
Standard of Care (SOC) agents
AbirateroneDrug
Standard of Care (SOC) agents
RuxolitinibDrug
Standard of Care (SOC) agents
AzacitidineDrug
Standard of Care (SOC) agents
| Study group | Role | What they receive |
|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Experimental | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma Receives: Drug: INCB057643 |
| Part1/Treatment Group A : 12mg QD INCB057643 | Experimental | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma Receives: Drug: INCB057643 |
| Part1/Treatment Group A : 16mg QD INCB057643 | Experimental | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.
Treatment Group A included solid tumors and lymphoma Receives: Drug: INCB057643 |
| Part1/Treatment Group B : 8mg QD INCB057643 | Experimental | 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 Receives: Drug: INCB057643 |
| Part1/Treatment Group B : 12mg QD INCB057643 | Experimental | 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. Receives: Drug: INCB057643 |
| Part1/Treatment Group C : 8mg QD INCB057643 | Experimental | 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 Receives: Drug: INCB057643 |
| Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Experimental | 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. Receives: Drug: INCB057643 |
| Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Experimental | 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. Receives: Drug: INCB057643 |
| Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Experimental | 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 Receives: Drug: INCB057643; Drug: Gemcitabine |
| Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Experimental | 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. Receives: Drug: INCB057643; Drug: Paclitaxel |
| Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Experimental | 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. Receives: Drug: INCB057643; Drug: Rucaparib |
| Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Experimental | 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 Receives: Drug: INCB057643; Drug: Abiraterone |
| Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Experimental | 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. Receives: Drug: INCB057643; Drug: Ruxolitinib |
| Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Experimental | 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 Receives: Drug: INCB057643; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From screening through at least 30 days after end of treatment, up to approximately 24 months
Secondary outcomes (9)
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.
Measured: 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
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)].
Measured: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months
Cmax: Maximum Observed Plasma Concentration of INCB057643.
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state.
Measured: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Tmax: Time to Maximum Plasma Concentration of INCB057643
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state
Measured: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
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
Measured: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1
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
Measured: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8
Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643.
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state.
Measured: C2D1
Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state
Measured: C2D1
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.
Measured: C2D1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2016 (estimated)
- Study start18 May 2016
- Primary completion13 Feb 2019
- Study completion13 Feb 2019
Why it stopped: Study terminated due to safety issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fred Zheng, MD, PhD, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02711137
- Sponsor's protocol ID
- INCB 57643-101
- Other IDs
- 2017-002641-29, 2017
- Status last verified
- Oct 2025
- First submitted
- 9 Mar 2016
- Last updated
- 21 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.
PubMed 31527168
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02711137
- Acronym / sponsor ID
- INCB 57643-101
- Conditions
- Solid Tumors
- Keywords
- Solid tumor, lymphoma, leukemia, AML, myelodysplastic syndrome (MDS), multiple myeloma, myeloproliferative neoplasm (MPN), MDS/MPN
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to safety issues.
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 18 May 2016 (actual)
- Primary completion
- 13 Feb 2019 (actual)
- Study completion
- 13 Feb 2019 (actual)
- First posted
- 17 Mar 2016 (estimated)
- Results
- Posted 28 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Part1/Treatment Group A : 8mg QD INCB057643 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643Initial 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 | Experimental | Drug: INCB057643, Drug: GemcitabineInitial 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 | Experimental | Drug: INCB057643, Drug: PaclitaxelInitial 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 | Experimental | Drug: INCB057643, Drug: RucaparibInitial 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 | Experimental | Drug: INCB057643, Drug: AbirateroneInitial 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 | Experimental | Drug: INCB057643, Drug: RuxolitinibInitial 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 | Experimental | Drug: INCB057643, Drug: AzacitidineInitial 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INCB057643Initial 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). | Drug | Part1/Treatment Group A : 12mg QD INCB057643, Part1/Treatment Group A : 16mg QD INCB057643, Part1/Treatment Group A : 8mg QD INCB057643, Part1/Treatment Group B : 12mg QD INCB057643, Part1/Treatment Group B : 8mg 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 |
| GemcitabineStandard of Care (SOC) agents | Drug | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg |
| PaclitaxelStandard of Care (SOC) agents | Drug | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg |
| RucaparibStandard of Care (SOC) agents | Drug | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg |
| AbirateroneStandard of Care (SOC) agents | Drug | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni |
| RuxolitinibStandard of Care (SOC) agents | Drug | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg |
| AzacitidineStandard of Care (SOC) agents | Drug | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAE's).
Time frame: 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.
9 secondary outcomes
Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay
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
Objective Response Rate (ORR) With INCB057643 in Solid Tumors
Time frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months
Cmax: Maximum Observed Plasma Concentration of INCB057643.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
Tmax: Time to Maximum Plasma Concentration of INCB057643
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8
AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1
AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy
Time frame: Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8
Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643.
Time frame: C2D1
Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643
Time frame: C2D1
AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy
Time frame: C2D1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31527168Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fred Zheng, MD, PhD study director
Incyte Corporation
18 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing INCB057643, Gemcitabine and Paclitaxel in people with Solid Tumors, run by Incyte Corporation at 18 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAE's). (time frame: From screening through at least 30 days after end of treatment, up to approximately 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02711137, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.