675 Safety and tolerability of magrolimab combination therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC)

BackgroundNovel 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 with RM-HNSCC (figure 1). 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.MethodsPatients in SRI1 with previously untreated RM-HNSCC received magrolimab+pembrolizumab+platinum+5-fluorouracil; patients 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 patients who received ≥1 dose of study drug. The incidence of DLTs was assessed using patients 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 patients could experience a DLT, or the magrolimab dose would be de-escalated and a new cohort would be assessed.ResultsAt least 6 patients from each SRI were considered DLT-evaluable. The safety analysis population consisted of 6 patients in SRI1 and 7 patients in SRI2. No DLTs were reported. Treatment-emergent AEs (TEAEs) occurred in 6/6 (SRI1) and 7/7 (SRI2) patients (table 1). The most common TEAEs observed in each SRI were fatigue (SRI1) and anemia (SRI2). TEAEs leading to magrolimab discontinuation occurred in 1/6 patients in SRI1 (fatigue) and 1/7 patients in SRI2 (oral cavity fistula unrelated to study drug). In SRI1, no deaths were reported; 3 deaths were reported as unrelated to study treatment and occurred after the DLT evaluation period in SRI2: oral cavity fistula, pneumonia, and disease progression (during long-term follow-up).ConclusionsThe observed safety profile was as expected based on the known toxicity profiles of the individual agents. M