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.

Keywords: TROP2; clinical trial; patient-reported outcome; resistance; reverse translation.

Graphical abstract

Figure 1

Study design for part I and part II of TROPHIT1. The initial first run-in part I enrolled 20 patients in a single-arm design (treatment with SG). In case of two objective responses and median PFS ≥4.3 months in part I, further 60 subjects will be enrolled in a randomized part II of the trial comparing SG with PC. Created with Biorender.com. CC, crossover; PC, physician’s choice; PFS, progression-free survival; R, randomization; S, screening; SG, sacituzumab govitecan.