Safety and Tolerability of Magrolimab Combination Therapy in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM-HNSCC)

Purpose/Objective(s) Novel combination therapies are needed to improve outcomes in RM-HNSCC. Magrolimab is a monoclonal antibody that blocks CD47, a “don't eat me” signal overexpressed on cancer cells. Magrolimab induces macrophage-mediated phagocytosis of tumor cells and may synergize with chemotherapy agents through enhancement of phagocytic signals. The phase 2 ELEVATE HNSCC multicenter, open-label study (NCT04854499) is evaluating magrolimab-containing regimens in patients (pts) with RM-HNSCC. Here, we report data from 2 safety run-ins (SRI1 and SRI2) designed to assess safety/tolerability and recommended phase 2 dose (RP2D) of magrolimab in combination with standard of care. Materials/Methods Pts in SRI1 with previously untreated RM-HNSCC received magrolimab+pembrolizumab+platinum+5-fluorouracil; pts in SRI2 with locally advanced or RM-HNSCC (1-2 lines of prior systemic therapy) received magrolimab+docetaxel. Magrolimab was first administered as a 1 mg/kg priming dose, followed by weekly 30 mg/kg doses for two 21-day cycles and then a maintenance dose of 60 mg/kg Q3W. Pembrolizumab and chemotherapy were given per standard of care. Primary endpoints of the SRI were incidence of adverse events (AEs) and dose-limiting toxicities (DLTs). Safety was assessed in pts who received ≥1 dose of study drug. The incidence of DLTs was assessed using pts who experienced a DLT during the DLT evaluation period or who completed ≥2 magrolimab and ≥1 combination agent doses. To select an RP2D, ≤2 of 6 DLT-evaluable pts could experience a DLT, or the magrolimab dose would be de-escalated and a new cohort would be assessed. Results At least 6 pts from each SRI were DLT-evaluable. The safety analysis population was 6 pts in SRI1 and 7 pts in SRI2. No DLTs were reported. Treatment-emergent AEs (TEAEs) occurred in 6/6 (SRI1) and 7/7 (SRI2) pts. In SRI1, the most common (≥4 pts) TEAEs were fatigue (5/6), diarrhea, nausea, decreased platelet count, stomatitis, and decreased white blood cell count (4/6 each). In SRI2, the most common (≥4 pts) TEAEs were anemia (5/7) and fatigue (4/7). TEAEs leading to magrolimab discontinuation occurred in 1/6 pts in SRI1 (fatigue) and 1/7 pts in SRI2 (oral cavity fistula unrelated to study drug). In SRI1, no deaths were reported; in SRI2, 3 deaths were reported as unrelated to study treatment and occurred after the DLT evaluation period: oral cavity fistula, pneumonia, and disease progression (during long-term follow-up). Conclusion The observed safety profile was as expected based on the known toxicity profiles of the individual agents. Magrolimab appears tolerable in these combinations. No DLTs or treatment-related deaths occurred. Magrolimab RP2D was declared at the initial dose level tested in both SRIs.