TROPHIT1—a randomized, open-label, multicenter, phase II/III trial of sacituzumab govitecan compared to standard of care in metastatic colorectal cancer patients

Abstract

Background

Colorectal cancer (CRC) ranks among the most common malignancies worldwide. Response rates to standard-of-care (SOC) treatment drop sharply beyond the second treatment line. Trophoblast cell surface antigen-2 (TROP2) acts in a plethora of cellular processes and ectopic expression is detected in a significant percentage of CRCs. Sacituzumab govitecan (SG) is composed of a TROP2-directed antibody armed with the topoisomerase inhibitor SN38. Thus, SG delivers SN38 to TROP2-expressing cancer cells. SG is approved for the treatment of metastatic breast cancer. Phase I/II data revealed a favorable safety profile and early signs of clinical activity in unselected metastatic CRC (mCRC).

Patients and methods

TROPHIT1 is an open-label, randomized, multicenter, phase II/III trial to investigate the efficacy of SG in mCRC. Patients being refractory to ≥2 lines of prior therapy and an irinotecan-free interval of at least 6 months are enrolled. In the first part of the study, 20 patients are enrolled in the single-agent SG arm. Upon clinical efficacy in the first part, additional 60 patients are randomized (1 : 1) in the second part to single-agent SG compared with SOC. The primary endpoint is progression-free survival. TROPHIT1 contains a translational research program to unravel the determinants of resistance.