A Phase I/Ib Study of Olaparib and ASTX727 in BRCA1/2- and HRD-mutated Tumors
Pamela Munster
Summary
This is a single center, phase I/Ib clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced/metastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and/or Checkpoint kinase 2 (CHEK2) mutations).
Description
PRIMARY OBJECTIVES: I. To assess the safety and tolerability of olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the homologous recombination repair (HRR) pathway. II. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) for olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the HRR pathway. SECONDARY OBJECTIVES: I. To evaluate the preliminary efficacy of the recommended dose level of olaparib and ASTX727 in patients with solid tumor malignancies and germline or som…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with: Phase I, Dose Escalation: Germline and/or somatic mutation\* in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2. Phase Ib, Dose Expansion\*\*: 1. Expansion Cohort A (n=6): Germline mutation\* (with or without accompanying somatic mutation) in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and/or CHEK2; 2. Expansion Cohort B (n=6): Germline and/or somatic mutation\* in one or more of the following gene…
Interventions
- DrugOlaparib
Given orally
- DrugASTX727
Given Orally
Location
- University of California, San FranciscoSan Francisco, California