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Background <p>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).</p> Objective <p>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.</p> Patients and Methods <p>A total of 78 patients were enrolled at eight study sites in the USA. In phase 1b, patients with advanced STs received weekly maintenance doses of magrolimab at 10–45 mg/kg and cetuximab at 200–250 mg/m<sup>2</sup> 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).</p> Results <p>The maximum tolerated dose was not reached in phase 1b. Two RP2Ds were explored in phase 2: magrolimab at 30 or 45 mg/kg plus cetuximab at 250 mg/m<sup>2</sup>. 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.</p> Conclusions <p>These results indicate tolerability and potential antitumor activity when combining anti-CD47 therapy and cetuximab in heavily pretreated patients with CRC.</p>

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A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors

  • 期刊论文

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  • 发表日期：

    2025年3月26日

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  • Cathy Eng,
  • Nehal J. Lakhani,
  • Philip A. Philip,
  • Charles Schneider,
  • Benny Johnson,
  • Adel Kardosh,
  • Mark P. Chao,
  • Amita Patnaik,
  • Fadi Shihadeh,
  • Yeonju Lee,
  • Kai Song,
  • Denise Jin,
  • Yanan Huo,
  • Michael Howland,
  • George A. Fisher,
  • J. Randolph Hecht

摘要

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

A total of 78 patients were enrolled at eight study sites in the USA. In phase 1b, patients with advanced STs received weekly maintenance doses of magrolimab at 10–45 mg/kg and cetuximab at 200–250 mg/m2 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

The maximum tolerated dose was not reached in phase 1b. Two RP2Ds were explored in phase 2: magrolimab at 30 or 45 mg/kg plus cetuximab at 250 mg/m2. 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.