open-label safety and tolerability study of incb057643 in subjects with advanced malignancies

Conditions: Solid Tumors

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. 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.


Eligibility criteria:
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

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 triple-hit myc bromodomain and extra-terminal (bet) inhibitor