Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation
Trial Parameters
Brief Summary
This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 administered by IV infusion on Day 1 and Day 8 of a 28-day cycle in patients with selected solid tumours and associated mutations for future Phase II trials. The safety and tolerability of CX-5461, preliminary evidence of antitumor effect and the effect of CX-5461 on the Health-Related Quality of Life (HRQoL) will also be evaluated. The study will also evaluate the predictive value of mutational signatures and explore the significance of dynamic changes in ctDNA levels and plasma DNA methylome profiling in this study's exploratory cohort.
Eligibility Criteria
Inclusion Criteria: Main study cohort: 1. Histologically or cytologically confirmed malignancy of the pancreas, prostate, breast, or ovary. 2. Documented evidence of pathogenic or likely pathogenic somatic or germline mutation in BRCA1/2 and/or PALB2, and/or any genetic alterations listed below as indicated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory report. The report must be submitted to and approved by study sponsor prior to registration. Other HRD-associated mutations could be eligible if prior approval by the sponsor is granted. ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CCNE1, CHEK1, CHEK2, CDK12, CREBBP, FANCA, FANCI, FANCL, FANC2, FANCB, FANCC, FANCD2, FANC family\*, MRE11A, MYC, NBN, NCL, PALB2, RAD50, RAD51B, RAD51C, RAD51D, RAD54L, SLFN11, PTIP, MLL3, MLL4, EZH2, CtIP(RBBP8), MUS81, CDH4, DYNLL11, TOPBP1, NBS1, CDC25A, CDC25C, RAD17, WEE1 \* In addition to the genes already specified, the "FANC family" genes may also include the following: FANCE, F