A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.

Summary

This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Interim PK and safety data from this cohort will be evaluated before initiating dose-escalation. In arm A, RO6839921 will be given to patients with advanced solid tumor malignancies. In Arm B, RO6839921 will be given to patients with relapsed/refractory acute myeloid leukemia (AML). The arms will escalate independently. Escalation will begin in solid tumor patients (Arm A) in single patient cohorts, using a new Continual Reassessment Method (n-CRM). Escalation for AML patients will be initiated at or below the dose level that causes \>/= Grade 2 hematologic side effects in Arm A. Escalation in AML patients will follow a rolling 6 design. In both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles. There will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.

Timeline

Start

2014-04-21

Primary completion

2018-05-07

Completion

2018-05-07

Publications

• Uy GL, Assouline S, Young AM, Blotner S, Higgins B, Chen LC, Yee K. Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia. Invest New Drugs. 2020 Oct;38(5):1430-1441. doi: 10.1007/s10637-020-00907-4. Epub 2020 Feb 4.
• Abdul Razak AR, Miller WH Jr, Uy GL, Blotner S, Young AM, Higgins B, Chen LC, Gore L. A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1156-1165. doi: 10.1007/s10637-019-00869-2. Epub 2019 Nov 16.

Drugs

Indications