The objective response rate (ORR) of patients with relapsed colorectal cancer enrolled in a phase 2 study of the combination of TRC102, a small-molecule inhibitor of the DNA base excisional repair (BER) pathway, and temozolomide, a DNA alkylating agent, was only 6%. The findings from this study were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019. Because the BER pathway is involved in the development of resistance to alkylating agents, the combination of temozolomide with the BER inhibitor, TRC102, was thought to represent a logical treatment approach. A phase 1/2 trial of this combination therapy was conducted in patients with refractory solid tumors and lymphomas (ClinicalTrials.gov Identifier: NCT01851369). In the phase 1 portion of the trial, the major dose-limiting toxicity was anemia, and the recommended phase 2 dose for most patients was 125 mg oral TRC102 plus 150 mg/m2 oral temozolomide once daily on days 1 through 5 of a 28-day cycle.
Source: Cancer Therapy Advisor