A Phase 1b Study of PEP07 (Checkpoint Kinase 1 Inhibitor) in Patients With Advanced Cancer
The goal of this clinical trial is * To assess the safety and tolerability of PEP07 administered orally as a single dose and at escalating dose levels, and, to determine the dose-limiting toxicity (DLT) of study treatment in patients with Acute Myeloid Leukemia (AML) and Mantle Cell Lymphoma (MCL). * To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of PEP07 monotherapy. Participants will receive PEP07 administered orally once daily (QD) for 2 consecutive days and 5 days off, every week for 4 weeks until disease progression, intolerable toxicity, confirmed pregnancy, death, consent withdrawal, HSCT or other anti-cancer treatment is required, or the Sponsor ends the study, whichever occurs first.
• Must be ≥ 18 years of age.
• Must have histological or cytological confirmation advanced hematologic malignancy including:
‣ Relapsed or refractory AML (by the 5th edition of World Health Organization \[WHO\] classification of Hematolymphoid tumors)
⁃ OR Relapsed or refractory MCL and have received at least two prior lines of treatment, including chemoimmunotherapy and BTKi and at least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma.
• Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
• Must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.
• Must have adequate liver function as demonstrated by:
‣ aspartate aminotransferase (AST) ≤ 2.5 × ULN
⁃ alanine aminotransferase (ALT) ≤ 2.5 × ULN
⁃ bilirubin ≤ 1.5 × ULN (unless considered due to leukemic organ involvement. Patients with Gilbert's Syndrome may have had a bilirubin \> 1.5 × ULN per discussion between the PI or designee and sponsor)
• Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram.
• Previous AEs have been improved to baseline or Grade ≤ 1 NCI CTCAE v5.0.
• Female patients with reproductive potential must have a negative serum pregnancy test 7 days prior to the administration of PEP07.
• Patients will be required to have a Covid negative test either via reverse transcriptase polymerase chain reaction (RTPCR) or a rapid antigen test (RAT) test on Day -7/Day 1.
⁃ Provision of signed and dated informed consent form.