Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia

This is a dose-finding study of oral PCLX-001 in patients with R/R AML. There are two parts to the study: Dose Escalation and Dose Expansion.

Dose Escalation will determine the minimum safe and biologically-effective dose of daily oral PCLX-001 in patients with R/R AML. The Bayesian optimal interval (BOIN) design will be used for dose escalation, informed by real-time assessment of safety, efficacy, PK and PD in each dose cohort. A maximum of 15 patients will enroll in the dose escalation part. Oral PCLX-001 will be provided as continuous daily dosing on a 28-day cycle. The starting dose will be 40 mg. AML patients will be evaluated for toxicity, PK, and the relationship between PK observed in this AML trial with universally co-administered CYP3A inhibitor drugs (as in this setting, azole antifungals are continuously administered to this population), in comparison with PK data derived from patients with NHL and solid tumors without co-administered CYP3A inhibitors. These data will be integrated to inform the decision on the minimum safe and biologically-effective dose to be used in the expansion cohort.

PCLX-001 will be administered as an oral daily dose on a 28-day cycle as per the dose level schedule below.

Dose Escalation Schedule: (1 cycle = 28 days)

1. Daily oral dose of 40mg 2. Daily oral dose of 70mg 3. Daily oral dose of 100mg 4. Daily oral dose of 140mg 5. Daily oral dose of 210mg 6. Daily oral dose of 280mg

Trial will start at 40mg based on results from an ongoing independent dose escalation trial in NHL and solid tumors. If DLT is not observed at the dose of 280 mg, this dose will be considered the minimum safe and biologically-effective dose to be used in the expansion cohort.

Dose expansion. 20 evaluable patients will be accrued and treated with the minimum safe and biologically-effective dose. PCLX-001 will be administered as an oral daily dose on a 28-day cycle to determine the safety and preliminary clinical activity of PCLX-001.

Dosing Administration PCLX-001 will be administered orally, once daily, on 28-day cycles, at the same time each day.