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