Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas

Inclusion Criteria

• •1. Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
• •2. Men and women 18 years of age or older.
• •3. Participants 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.
• •a. For Phase 2 Cohort 3, participants must have histologically confirmed PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study: adult T-cell lymphoma/leukemia, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, nodal peripheral T-cell with T-follicular helper (THF) phenotype, and anaplastic large-cell lymphoma.
• •4. For Phase 2 Cohorts 3 and 4, participants must have evidence of documented progressive disease and must have received at least two prior systemic therapies.
• •1. Participants with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin, provided that brentuximab vedotin is locally approved and available.
• •2. Participants with mycosis fungoides or Sezary syndrome must have received, be ineligible or intolerant to mogamulizumab, provided that mogamulizumab is locally approved and available.
• •5. In the Phase 2 portion of the protocol only, participants must have measurable disease according to response criteria appropriate for their type of cancer.
• •a. For Phase 2 Cohort 3 (PTCL), measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion \>1.5 cm or extranodal lesions \>1.0 cm) is required.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• •7. Acceptable organ function, as evidenced by the following laboratory data:
• •1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.0 \* upper limit of normal (ULN).
• •2. Total serum bilirubin \<=1.5 \* ULN
• •3. Absolute neutrophil count (ANC):
• •* Phase 1 and 2 (except Phase 2 participants with known lymphoma; ie, not applicable for Cohorts 3 or 4) \>=1500 cells/mm3
• •* Phase 2 participants with known lymphoma: \>=1000 cells/mm3 (\>750 cell/mm3 for participants with lymphoma in bone marrow)
• •4. Platelet count:
• •* Phase 1 and 2 (except Phase 2 participant with known lymphoma; ie, not applicable for Cohorts 3 or 4) \>=100,000 cells/mm3
• •* Phase 2 participants with known lymphoma: \>= 50,000 cells/mm3; \>=25,000 cells/mm3 for participants with lymphoma in bone marrow
• •5. Serum creatinine levels \<= 1.5 \* ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measure creatinine clearance \>=50 mL/min.
• •6. Amylase and lipase \<=ULN.
• •8. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group \[CTFG\]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control (as described in the protocol) and must agree not to become pregnant or father a child while receiving treatment with study drug and for at least 3 months after completing treatment. Contraceptive measures which may be considered highly effective comprise combined hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of birth control.