This is an open-label, dose-escalation Phase 1/2 Study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regiment, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging measures are not available.
- Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
- Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
- Subjects must have measurable disease according to RECIST v1.1, or evaluable disease that can be reliably and consistently followed.
- Hypersensitivity to ASTX660, excipients of the drug product, or other components of the safety treatment regimen.
- Poor medical risk because of systemic diseases (e.g. active uncontrolled infections) in addition to the qualifying disease under study.
- Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subjects safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of ASTX660.
There are 2 phases in this study, Phase 1 (early stage) and Phase 2 (later stage). Phase 1 has now been completed. You are being asked to participate in the Phase 2 part of this study.
The following tumor types are planned for study in Phase 2:
- Cohort 1: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy.
- Cohort 2: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
- Cohort 3: Progressive or relapsed peripheral T-cell lymphoma (PTCL).
- Cohort 4: Relapsed or refractory cutaneous T-cell lymphoma (CTCL).
- Cohort 5: Other tumors types that are characterized by a molecular feature may confer sensitivity to ASTX660 (e.g. oncogenic activation of the NF-ϰB pathway or documented amplification of the gene loci encoding c-IAP1 or c-IAP2), pending confirmation in writing by the Astrex medical monitor.
- Cohort 6: Cervical carcinoma not responsive or relapsed after standard therapy.
Each 28-day treatment cycle will consist of 2 periods of 1 week on and 1 week off study treatment.
Study visits will take place frequently during Cycles 1 and 2, and less frequently thereafter. Serial blood samples will be collected for PK, PD, and exploratory biomarker analysis at specific time points.
Fresh tumor biopsies are required during screening and posttreatment Cycle 2, if it is clinically and safely feasible to do so. If a sample of your tumor was previously collected and stored at a clinic ("archived biopsy sample"), it will be obtained during screening for use in this study, if available. These samples will be used to characterize the genetic background of the tumor.
CT and MRI scans are performed at screening, at the end of Cycle 2 (Week 4), at the end of Cycle 4, Cycle 6, Cycle 9, and every 3 months thereafter. This frequency is considered standard of care treatment.
The total amount of blood that will be needed for all of the screening tests will be about 4 teaspoons (or 20mL). No more than 250mL (about 1 cup or half a pint) of blood will be collected in any one cycle (of 28 days).
Overall, the study sponsor excepts to enroll 200 subjects in this study. It is expected that up to 10 subjects will be enrolled at Tufts Medical Center.