Phase II randomised study of magrolimab combined with bevacizumab-FOLFIRI in patients with previously treated advanced inoperable metastatic colorectal cancer.

Effective treatment for metastatic colorectal cancer (mCRC) remains an unmet need. CD47 overexpression on mCRC cells is associated with a poor prognosis. The ELEVATE CRC study evaluated magrolimab (CD47 inhibitor) plus bevacizumab-5-fluorouracil, irinotecan and leucovorin (FOLFIRI) in mCRC. This open-label, phase II study enrolled eligible patients with previously treated advanced inoperable mCRC. The safety run-in (SRI) cohort's primary objective was to evaluate the safety, tolerability and recommended phase II dose of magrolimab plus bevacizumab-FOLFIRI. After SRI, patients were randomly assigned (2:1) to receive magrolimab plus bevacizumab-FOLFIRI (magrolimab) or bevacizumab-FOLFIRI (control). The randomised cohort's primary endpoint was progression-free survival (PFS). No dose-limiting toxicities occurred in the SRI cohort (10 patients). In the randomised cohort (67 patients), median PFS was 6.2 versus 6.7 months in the magrolimab (44 patients) versus control (23 patients) arm (hazard ratio 0.956, 95% confidence interval 0.339-2.691). However, early study closure limits PFS interpretation. Grade ≥3 adverse event (AE) rates were 72.7% versus 52.4% in magrolimab versus control arms. Across cohorts, two AE-related deaths occurred in patients treated with magrolimab; neither was considered treatment-related. Adding magrolimab to bevacizumab-FOLFIRI increased grade ≥3 AE incidence and did not improve efficacy outcomes, highlighting a continuing unmet therapeutic need in mCRC.