Phase II study of magrolimab combination therapies in patients with head and neck squamous-cell carcinoma

The phase II ELEVATE HNSCC study evaluated magrolimab combinations in metastatic head and neck squamous-cell carcinoma (mHNSCC).

Eligible patients had previously untreated recurrent/mHNSCC (untreated cohort) or pretreated advanced/mHNSCC (pretreated cohort). Safety run-in (SRI) evaluations were followed by phase II assessments. In the SRI, the untreated cohort received magrolimab (M), pembrolizumab (Pem), and platinum/5-fluorouracil (PF) chemotherapy (MPemPF). In phase II, this cohort was randomized to MPemPF, PemPF, or M plus zimberelimab (Zim) and PF (MZimPF). The pretreated cohort received magrolimab plus docetaxel (MDtx; SRI and phase II). SRI primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase II primary endpoints were progression-free survival (PFS; untreated recurrent/mHNSCC) and objective response rate (ORR; pretreated advanced/mHNSCC).

No DLTs occurred in the SRIs. In phase II, median PFS in the untreated cohort was 5.5 months with MPemPF (52 patients) versus 5.6 months with PemPF (54 patients; hazard ratio 1.314, 95% confidence interval 0.809-2.136). ORR was 12.2% in the pretreated cohort (41 patients). Grade 3-4 AE rates were 88.5% (MPemPF), 71.7% (PemPF), and 85.4% (MDtx). Across cohorts, 12 fatal AEs occurred (none magrolimab-related).

There was no benefit observed with magrolimab treatment. The study closed prematurely, limiting interpretation.