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

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