advanced malignaties several types of severe cancer
Conditions
Interventions
INCB059872 will be self-administered orally QOD on a 28-day cycle. In each
cycle of the QOD dosing schedule, subjects should receive 14 doses of
INCB059872. Tablets will be available in 1 mg strengt
Sponsors
Incyte Biosciences UK Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, age 18 years or older. 2. Presence of measurable disease that has been confirmed by histology or cytology. Myelofibrosis subjects must have palpable spleen of * 5 cm below the left subcostal margin on physical examination at the screening visit. 3. The following malignancy types will be included in each of the treatment groups: * Part 1 (Dose Escalation) Treatment Group A: AML or myelodysplastic syndrome (MDS) Treatment Group B: SCLC (other solid tumors, eg, endocrine tumors, are allowed with medical monitor approval) * Part 2 (Dose Expansion) Treatment Group A1: Relapsed/refractory AML or MDS Treatment Group A2: MF (PMF, PPV-MF, and PET-MF) Treatment Group B1: SCLC Treatment Group B2: Ewing's sarcoma and poorly differentiated neuroendocrine tumors * Parts 3 and 4 (Combination Dose Escalation/Expansion) Treatment Group C/C1: Relapsed/refractory AML Treatment Group D/D1: Newly diagnosed, treatment-naive AML, or MDS who are unfit to tolerate standard intensive chemotherapy at study entry and who are eligible to receive azacitidine as first-line therapy for the disease under study. Treatment Group E/E1: SCLC previously progressed on platinum-based treatment 4. Subjects must meet specific disease and treatment criteria as follows: * TG A/A1/A2, TG B/B1/B2, C/C1, and TG E/E1: The subject must not be a candidate for potentially curative therapy or standard-of-care approved therapy. * TG A2: The subjects must have confirmed diagnosis of PMF, PPV-MF, or PET-MF according to revised WHO 2016 criteria. * TG D/D1: Subjects with newly diagnosed, treatment-naive AML who are unfit to tolerate standard intensive chemotherapy at study entry based on at least 1 of the following criteria: * Age * 75 years old * History of congestive heart failure (CHF) or documented ejection fraction (EF) * 50% * Pulmonary disease with diffusing capacity of the lungs for carbon monoxide* 65% or FEVI * 65%, or dyspnea at rest or requiring oxygen * Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy OR Subjects with newly diagnosed, treatment-naïve, IPSS-R intermediate or higher risk disease MDS who have at least 5% bone marrow blasts, who are unfit to tolerate standard intensive chemotherapy at study entry and who are eligible to receive azacitidine as first-line therapy for the disease under study. The following treatments for prior lower risk MDS are acceptable: Revlimid®, low-dose cytarabine, and growth factors. * TG E/E1: The subjects in TG E must have previously received platinum-based therapy, but additional lines of therapies are allowed. The subjects in TG E1 must not have received more than 1 previous line of therapy for locally advanced or metastatic SCLC. The previous line of therapy must be a platinum-based therapy, and the subjects must have progressed on or after this treatment. 5. Willingness to undergo a pretreatment bone marrow biopsy or aspirate (AML/MDS/MF) during screening (may be waived with medical monitor approval). For subjects with solid malignancies, must have baseline archival tumor specimen available: a tumor block or approximately 15 slides from biopsy or resection of primary tumor or metastasis that are 2 years old may be accepted with medical monito
Exclusion criteria
Exclusion criteria: 1. Receipt of anticancer medications, anticancer therapies, or investigational drugs within the following interval before the first administration of study drug (requirement may be waived with medical monitor approval): a. 1.5 × institutional upper limit of normal (ULN) if no liver metastases or > 3 × ULN in the presence of liver metastases or presence of documented Gilbert syndrome (unconjugated hyperbilirubinemia). b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 × institutional ULN. c. Creatinine clearance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Parts 1 and 2: Safety and tolerability as assessed by monitoring frequency, duration, and severity of adverse events (AEs) through physical examinations, by evaluating changes in vital signs and electrocardiograms (ECGs), and through clinical laboratory blood and urine sample evaluations. * Parts 3 and 4: Safety and tolerability as assessed by monitoring frequency, duration, and severity of AEs through physical examinations, by evaluating changes in vital signs and ECGs, and through clinical laboratory blood and urine sample evaluations in combinations therapies. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Parts 1 and 2: Tumor response rates in those subjects with measurable disease or spleen volume changes as determined by investigator assessment of response per disease-specific guidelines. * Solid tumors: Objective response rate (ORR), defined as the percentage of subjects having complete response (CR) or partial response (PR) will be determined by the investigator assessment of radiographic disease assessments per RECIST v1.1. * Acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS): ORR, defined as the proportion of subjects who achieve CR or complete remission with incomplete hematologic recovery (CRi) per the International Working Group Response Criteria for Acute Myeloid Leukemia or the International Working Group Response Criteria for MDS, as applicable. * MF: Change and percentage change in spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI; computed tomography [CT] scan in subjects who are not a candidate for MRI or when MRI is not readily available) at Week 12 when compared with baseline. * Parts 3 and 4: Tumor response rates in those subjects with measurable disease as determined by investigator assessment of response per disease-specific guidelines. * Small cell lung cancer (SCLC): ORR, defined as the percentage of subjects having CR or PR will be determined by the investigator assessment of radiographic disease assessments per RECIST v1.1. * AML/MDS: ORR, defined as the proportion of subjects who achieve CR or CRi per the International Working Group Response Criteria for Acute Myeloid Leukemia or the International Working Group Response Criteria for MDS, as applicable. * PK parameters of INCB059872 in plasma: Cmax, Tmax, Cmin, AUC0-t, t*, and Cl/F. Exploratory Endpoints: * Parts 1 and 2: * Efficacy measured by * Solid tumor, AML, and MDS: Duration of response, progression-free survival, and overall survival. * MF: Change and percentage change in spleen volume reduction (SVR) as measured by | — |
Countries
Netherlands
Outcome results
None listed