Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
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ClinicalTrials.gov Identifier: NCT02711137 |
Recruitment Status :
Terminated
(Study terminated due to safety issues.)
First Posted : March 17, 2016
Results First Posted : April 28, 2022
Last Update Posted : April 28, 2022
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Solid Tumors | Drug: INCB057643 Drug: Gemcitabine Drug: Paclitaxel Drug: Rucaparib Drug: Abiraterone Drug: Ruxolitinib Drug: Azacitidine | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 137 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies |
Actual Study Start Date : | May 18, 2016 |
Actual Primary Completion Date : | February 13, 2019 |
Actual Study Completion Date : | February 13, 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: 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 |
Drug: INCB057643
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). |
Experimental: 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 |
Drug: INCB057643
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). |
Experimental: 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 |
Drug: INCB057643
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). |
Experimental: 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
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Drug: INCB057643
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). |
Experimental: 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.
|
Drug: INCB057643
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). |
Experimental: 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
|
Drug: INCB057643
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). |
Experimental: 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.
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Drug: INCB057643
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). |
Experimental: 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.
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Drug: INCB057643
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). |
Experimental: 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
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Drug: INCB057643
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). Drug: Gemcitabine Standard of Care (SOC) agents |
Experimental: 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.
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Drug: INCB057643
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). Drug: Paclitaxel Standard of Care (SOC) agents |
Experimental: 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.
|
Drug: INCB057643
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). Drug: Rucaparib Standard of Care (SOC) agents |
Experimental: 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
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Drug: INCB057643
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). Drug: Abiraterone Standard of Care (SOC) agents |
Experimental: 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.
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Drug: INCB057643
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). Drug: Ruxolitinib Standard of Care (SOC) agents |
Experimental: 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
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Drug: INCB057643
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). Drug: Azacitidine Standard of Care (SOC) agents |
- 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.
- 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 ]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.
- 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 ]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. [ Time Frame: 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 [ Time Frame: 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
- 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 ]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
- 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 ]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. [ Time Frame: C2D1 ]Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state.
- Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643 [ Time Frame: C2D1 ]Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state
- AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy [ Time Frame: C2D1 ]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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02711137

Study Director: | Fred Zheng, MD, PhD | Incyte Corporation |
Documents provided by Incyte Corporation:
Responsible Party: | Incyte Corporation |
ClinicalTrials.gov Identifier: | NCT02711137 |
Other Study ID Numbers: |
INCB 57643-101 |
First Posted: | March 17, 2016 Key Record Dates |
Results First Posted: | April 28, 2022 |
Last Update Posted: | April 28, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Neoplasms Gemcitabine Paclitaxel Azacitidine Rucaparib INCB057643 Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators |
Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Poly(ADP-ribose) Polymerase Inhibitors |