A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors
Cathy Eng, Nehal J. Lakhani, Philip A. Philip, Charles Schneider, Benny Johnson, Adel Kardosh, Mark P. Chao, Amita Patnaik, F. Shihadeh, Yeon‐Ju Lee, Kai Song, Denise Jin, Yanan Huo, Michael F. Howland, George A. Fisher, J. Randolph Hecht
Abstract
BACKGROUND: Chemotherapy plus epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, is standard therapy for KRAS wild-type (KRASwt) colorectal cancer (CRC); however, responses are infrequent. Magrolimab is a monoclonal antibody targeting CD47, an antiphagocytic signal overexpressed in solid tumors (STs). OBJECTIVE: This open-label, multicenter phase 1b/2 study (NCT02953782) aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety, tolerability, and efficacy of magrolimab + cetuximab in patients with advanced CRC or other STs. PATIENTS AND METHODS: following 3 + 3 dose-escalation. In phase 2, patients with anti-EGFR-refractory CRC received magrolimab + cetuximab at RP2Ds. Primary endpoints were dose-limiting toxicities, adverse events, and objective response rate (ORR; phase 2). RESULTS: . Most common treatment-related adverse events (TRAEs) were dermatitis acneiform (35.9%), infusion-related reactions (33.3%), dry skin (32.1%), fatigue (32.1%), and headache (29.5%). Most common grade ≥ 3 TRAEs were anemia (11.5%), increased blood bilirubin (9.0%), and decreased lymphocyte count (9.0%). Discontinuation of any study treatment owing to TRAEs occurred in 3.8% of patients. No deaths occurred due to TRAEs. In phase 2, ORR was 6.3% and 0% in the KRASwt and KRASmt CRC cohorts, respectively; disease control rate was 50.0% and 38.1%, and median overall survival was 9.5 and 7.6 months, respectively. CONCLUSIONS: These results indicate tolerability and potential antitumor activity when combining anti-CD47 therapy and cetuximab in heavily pretreated patients with CRC.