A phase 1 trial of TRC102 (methoxyamine HCl) with temozolomide (TMZ) in patients with solid tumors and lymphomas.

Abstract

2518Background: TRC102 inhibits BER by binding to abasic sites and acting as a topo II poison to cause DNA strand breaks; it potentiates the activity of alkylating agents including TMZ in murine models. In xenograft studies, TRC102 efficiently enhanced the antitumor effect of TMZ regardless of cell line genetic characteristics, e.g., O6-methylguanine DNA-methyltransferase, mismatch repair (MMR), or p53 status. This is the first report for the expansion phase (the escalation phase was reported previously (ASCO2016)). Methods: We conducted a phase 1 trial of TRC102with TMZ in patients (pts) with refractory solid tumors. Eligibility criteria included adults that had progressed on standard therapy, ECOG PS of 0-2, and adequate organ function. TRC102 and TMZ were given orally days 1-5, in 28-day cycles. The pharmacokinetic and pharmacodynamic profile of TRC102 with TMZ was evaluated. Antitumor responses were determined using RECIST 1.1 criteria. The DNA damage response (DDR) markers γH2Ax, pNbs1, and Rad51 wer...