Trial results for a Phase 2 study (NCT04854499) evaluating pembrolizumab in combination with magrolimab for Head and Neck Squamous Cell Carcinoma were posted on ClinicalTrials.gov on 2025-11-19. The study, which was terminated, showed a median progression-free survival (PFS) of 5.5 months for the combination arm compared to 5.6 months for the control arm receiving pembrolizumab plus chemotherapy.

Background

Pembrolizumab (Keytruda) is an established immunotherapy. This study investigated its use in combination with magrolimab for the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC).

Trial design

The Phase 2 study (NCT04854499) was designed to evaluate the safety, tolerability, dosing, and effectiveness of magrolimab in combination with other anticancer therapies in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). The trial enrolled 193 participants and was ultimately TERMINATED. Key intervention arms included a combination of magrolimab, pembrolizumab, platinum, and 5-FU, compared against pembrolizumab, platinum, and 5-FU alone. Another arm investigated magrolimab in combination with docetaxel.

Key results

Key results were reported for safety and efficacy endpoints. Regarding safety, the percentage of participants experiencing Dose Limiting Toxicities (DLTs) was 0% in both the safety run-in cohort receiving magrolimab + pembrolizumab + platinum + 5-FU and the cohort receiving magrolimab + docetaxel. However, the percentage of participants experiencing Grade 3 or 4 laboratory abnormalities was higher, at 83.3% for the magrolimab + pembrolizumab + platinum + 5-FU cohort and 71.4% for the magrolimab + docetaxel cohort.

For efficacy, median Progression-free Survival (PFS) in Phase 2 Cohort 1 Arm A (magrolimab + pembrolizumab + platinum + 5-FU) was 5.5 months. In comparison, Phase 2 Cohort 1 Arm B (pembrolizumab + platinum + 5-FU) showed a median PFS of 5.6 months. The Objective Response Rate (ORR) for Phase 2 Cohort 3 (magrolimab + docetaxel) was 12.2%.

What this means

The results from this terminated Phase 2 trial suggest that adding magrolimab to a regimen of pembrolizumab, platinum, and 5-FU did not provide an improvement in median Progression-free Survival for patients with Head and Neck Squamous Cell Carcinoma, with both arms showing very similar outcomes (5.5 months vs 5.6 months). While Dose Limiting Toxicities were not observed, the high rates of Grade 3 or 4 laboratory abnormalities indicate a notable safety burden. The termination of the study further implies that the combination therapy did not meet the predefined criteria for continued development in this setting.

Source

The results for study NCT04854499 were posted on 2025-11-19 on ClinicalTrials.gov. The study, titled 'Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma,' is publicly available on clinicaltrials.gov.