439TiP A phase II (ph2), randomized study of magrolimab with bevacizumab and FOLFIRI in previously treated patients with advanced inoperable metastatic colorectal cancer (mCRC)

Abstract

For patients (pts) with mCRC who are ineligible/unable to derive benefit from novel targeted therapies or immunotherapies, standard of care (SOC) doublet or triplet chemotherapy-based regimens associated with toxicity and limited responses are the only available treatment options. Magrolimab is an antibody blocking CD47, a “don’t eat me” signal on cancer cells, resulting in tumor phagocytosis by macrophages and nonclinical activity in hematologic and solid tumor malignancies. Chemotherapeutic agents can enhance prophagocytic signals on tumor cells, leading to the potential for synergistic antitumor activity with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab with bevacizumab + FOLFIRI in advanced inoperable mCRC. This ph2, randomized, open-label study consists of safety run-in and ph2 cohorts. Eligible pts (≥18 y) progressed on or after 1 prior systemic therapy with chemotherapy based on 5-FU with oxaliplatin and bevacizumab. Magrolimab is administered intravenously with an initial 1-mg/kg priming dose to mitigate on-target anemia, followed by a 30-mg/kg dose during cycle 1 (28-day cycles) in the safety run-in to determine a recommended ph2 dose (RP2D) and evaluate pharmacokinetics and immunogenicity. In ph2, pts will be randomized 2:1 to magrolimab in combination with bevacizumab + FOLFIRI vs bevacizumab + FOLFIRI. After the magrolimab priming dose on day (D)1, the RP2D will be administered weekly starting on D8 for the next 6 doses, followed by every other week. Bevacizumab is administered at 5 mg/kg on D1 and D15 each cycle. FOLFIRI is administered per SOC on D1, D2, D15, and D16 of each cycle. Pts may continue treatment until unacceptable toxicity, progressive disease by RECIST 1.1, or pt/investigator choice. Primary endpoints include incidence of dose-limiting toxicities and adverse events (safety run-in) and PFS by investigator (ph2). Secondary endpoints include magrolimab concentration vs time, antidrug antibodies (safety run-in), objective response rate, PFS by independent central review, duration of response, and overall survival (ph2). NCT05330429. Gilead Sciences Inc.