Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma

Conditions

• Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Magrolimab — DRUG
  Administered intravenously
• Pembrolizumab — DRUG
  Administered intravenously
• Docetaxel — DRUG
  Administered intravenously
• 5-FU — DRUG
  Administered intravenously
• Cisplatin — DRUG
  Administered intravenously
• Carboplatin — DRUG
  Administered intravenously
• Zimberelimab — DRUG
  Administered intravenously

Study Details

The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of the study drug, magrolimab in combination with other anticancer therapies in participants with head and neck squamous cell carcinoma (HNSCC).

Key Dates

Start date

Sep 7, 2021

Status verified

Nov 2025

Primary completion

Oct 2, 2024

Completion

Oct 2, 2024

Study Design

Enrollment

193 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
  Participants with untreated metastatic or unresectable, locally recurrent head and neck squamous cell carcinoma (HNSCC) regardless of programmed cell death ligand 1 (PD-L1) status will receive the following: * magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses * pembrolizumab 200 mg on Day 1 of each cycle * 5-fluorouracil (5-FU) 1000 mg/m\^2/day Days 1-4 of each cycle (for up to 6 cycles) * platinum chemotherapy (cisplatin 100 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC) 5 per investigator choice (for up to 6 cycles)) Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the recommended Phase 2 dose (RP2D) is determined. Each cycle is 21 days.
• Experimental: Safety Run-in Cohort 2, Magrolimab + Docetaxel
  Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive the following: * magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, beginning at Day 8 and for the next 5 doses * docetaxel 75 mg/m\^2 on Day 1 of each cycle Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
• Experimental: Pre-expansion Safety Run-in Cohort, Magrolimab + Pembrolizumab
  The pre-expansion safety run-in cohort may be conducted at the sponsor's discretion prior to the initiation of Phase 2 Cohort 2. Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days. Participants will continue treatment until unacceptable toxicity or disease progression, whichever occurs first, and will not change their magrolimab dose level after the RP2D is determined. Each cycle is 21 days.
• Experimental: Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)
  Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m\^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m\^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
• Active Comparator: Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)
  Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive pembrolizumab 200 mg on Day 1 of each cycle, 5-FU 1000 mg/m\^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m\^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
• Active Comparator: Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)
  Participants with untreated metastatic or unresectable, locally recurrent HNSCC regardless of PD-L1 status will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, zimberelimab 360 mg on Day 1 of each cycle, 5- FU 1000 mg/m\^2/day Days 1-4 of each cycle, and platinum chemotherapy (cisplatin 100 mg/m\^2 or carboplatin AUC 5 per investigator choice). Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Zimberelimab therapy will be administered up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first. 5-FU and platinum chemotherapy will be administered for up to 6 cycles or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
• Experimental: Phase 2 Cohort 2, Magrolimab + Pembrolizumab
  Participants with untreated metastatic or unresectable, locally recurrent HNSCC with a PD-L1 combined positive score (CPS) ≥ 1 will receive magrolimab at the RP2D determined in the Safety run-in cohort 1 and pembrolizumab 200 mg on Day 1 of each cycle. Each cycle is 21 days. Magrolimab will be continued until loss of clinical benefit, unacceptable toxicity, or death. Pembrolizumab therapy will be administered for up to 24 months or until loss of clinical benefit or unacceptable toxicity, whichever occurs first.
• Experimental: Phase 2 Cohort 3, Magrolimab + Docetaxel
  Participants with locally advanced/metastatic HNSCC regardless of PD-L1 status who were previously treated with at least 1 and no more than 2 lines of prior systemic therapy will receive magrolimab at the RP2D determined in the Safety run-in cohort 2 and docetaxel 75 mg/m\^2 on Day 1 of each cycle. Each cycle is 21 days. Magrolimab and docetaxel will be continued until loss of clinical benefit, unacceptable toxicity, or death.

Primary Outcome Measure

Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 [ Time Frame: First dose date up to 21 days ]

Locations (22)

Related coverage on Hipa.ai

• Pembrolizumab/Magrolimab Combo Shows Similar PFS to Pembrolizumab Alone in HNSCC
  Pembrolizumab · Nov 19, 2025 · ClinicalTrials.gov

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