A Phase 2 Study of Magrolimab Combination Therapy in Patients with Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Novel combination therapies are needed to extend the survival of patients with recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC). Magrolimab is a humanized monoclonal antibody that blocks the immune checkpoint CD47, a "do not eat me" signal, overexpressed on cancer cells. Magrolimab binding to CD47 leads to phagocytosis of cancer cells and enhances antitumor efficacy through stimulation of both innate and adaptive immune responses. The current study (NCT04854499) is investigating the safety, tolerability, recommended Phase 2 dose (RP2D), and efficacy of three experimental magrolimab-containing regimens: 1) magrolimab + pembrolizumab + 5-fluorouracil + platinum (cisplatin or carboplatin) [MPFP]; 2) magrolimab + pembrolizumab (MP); and 3) magrolimab + docetaxel (MD). <h3>Materials/Methods</h3> This Phase 2, open-label study includes two safety run-in cohorts and three Phase 2 cohorts. The primary endpoints of the two run-in cohorts are to evaluate the incidence of adverse events and laboratory abnormalities as dose-limiting toxicities with MPFP in patients with untreated RM-HNSCC, and with MD in patients with RM-HNSCC treated with 1 to 2 lines of prior systemic therapy. The primary endpoints of Phase 2 are to evaluate the progression-free survival with MPFP versus PFP in patients with untreated RM-HNSCC (cohort 1), and the investigator-assessed objective response rates with MP in patients with untreated RM-HNSCC with PD-L1 CPS ≥1 (cohort 2) and with MD in patients with RM-HNSCC treated with 1 to 2 lines of prior systemic therapy (cohort 3). Magrolimab is administered IV on days 1, 8 and 15 of cycles 1 and 2, and day 1 of cycle 3 onward. Pembrolizumab, 5-fluorouracil, cisplatin, carboplatin, and docetaxel will be administered according to manufacturer's prescribing information. Patients will continue treatment until unacceptable toxicity or disease progression. Planned enrollment is ∼233 participants. Recruitment is ongoing. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD