What side effects are associated with this type of intervention?

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC), particularly those similar to Magrolimab (an anti-CD47 monoclonal antibody), often involve immunotherapies and targeted therapies. These treatments can lead to immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Targeted therapies like cetuximab may cause infusion reactions, skin rash, hypomagnesemia, and gastrointestinal issues. Combining these therapies can enhance their effectiveness but may also increase the risk of compounded side effects.

What prior FDA approvals exist?

Prior FDA approvals for the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC) include immunotherapies such as pembrolizumab and nivolumab, which are PD-1 inhibitors approved for patients previously treated with platinum-based chemotherapy. Cetuximab, an anti-EGFR monoclonal antibody, is also used in combination with chemotherapy. These treatments enhance the immune system's ability to target cancer cells, similar to the mechanism of Magrolimab, which promotes phagocytosis of cancer cells by blocking the 'don't eat me' signal.

What other types of research exist?

Promising novel alternatives to Magrolimab for HNSCC patients include immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways. Additionally, combination therapies involving these checkpoint inhibitors with other agents like chemotherapy or other immunotherapies (e.g., ipilimumab) are being actively studied and have shown efficacy in clinical trials.

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Chemotherapy

Magrolimab Combo for Cancer (ELEVATE HNSCC Trial)

Phase 2

Waitlist Available

Research Sponsored by Gilead Sciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

HNSCC per protocol specified inclusion criteria regardless of PD-L1 status

Should not have had prior systemic therapy administered in the recurrent or metastatic setting

Must not have

Prior treatment with a taxane

Prior treatment with any of the following: Anti-programmed cell death protein 1 or anti-PD-L1 checkpoint inhibitors, Anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing magrolimab, a drug that helps the immune system fight cancer, in combination with other treatments. It focuses on patients with head and neck squamous cell carcinoma. Researchers aim to find out if this combination is safe and effective.

Who is the study for?

This trial is for individuals with head and neck squamous cell carcinoma who haven't had systemic therapy in the recurrent/metastatic setting. Eligible tumor locations include oropharynx, oral cavity, hypopharynx, and larynx but not nasopharynx. Participants should have no more than two prior systemic therapies for advanced cancer and can't join if they've had certain immune treatments or a history of pneumonitis.

What is being tested?

The study tests magrolimab's safety and effectiveness when combined with other cancer drugs (Docetaxel, 5-FU, Cisplatin, Carboplatin) in patients with head and neck cancers. It aims to determine proper dosing and tolerability of this combination therapy.

What are the potential side effects?

Potential side effects may include allergic reactions to medication components, fatigue from treatment regimens, digestive issues like nausea or diarrhea from chemotherapy drugs, blood disorders such as anemia or clotting problems due to bone marrow suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have head and neck cancer, PD-L1 status doesn't matter.

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I haven't had systemic therapy for cancer that came back or spread.

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My head or neck cancer has spread or returned and cannot be cured with surgery or radiation.

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My cancer is advanced but has been treated with 1 or 2 systemic therapies.

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My cancer is in my throat, mouth, or voice box, but not in the upper part of my throat behind the nose.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with a taxane before.

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I have been treated with medications targeting immune checkpoints.

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I have had pneumonitis treated with steroids or have it now.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 2 Cohorts 1: Progression-free Survival (PFS)

Phase 2 Cohorts 2 and 3: Objective Response Rate (ORR)

Secondary study objectives

Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)

Phase 2 Cohorts: Change from Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life - Head and Neck Module (EORTC QLQ-H&N35)

Phase 2 Cohorts: Change from Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) Score

+4 more

Side effects data

From 2020 Phase 1 & 2 trial • 78 Patients • NCT02953782

67%

Abdominal pain

33%

Infusion related reaction

33%

Malignant neoplasm progression

33%

Performance status decreased

33%

Pyrexia

33%

Pain

33%

Gait disturbance

33%

Lactic acidosis

33%

Hypotension

33%

Hyperhidrosis

33%

Gastrooesophageal reflux disease

33%

Headache

33%

Deafness

33%

Vomiting

33%

Pollakiuria

33%

Diarrhoea

33%

Rash maculo-papular

33%

Nausea

33%

Aspartate aminotransferase increased

33%

Blood alkaline phosphatase increased

33%

Blood bilirubin increased

33%

Blood lactate dehydrogenase increased

33%

Mental disorder

33%

Constipation

100%

80%

60%

40%

20%

Study treatment Arm

Magrolimab Priming Dose Only

Magrolimab 45 mg/kg

Magrolimab 10 mg/kg

Magrolimab 20 mg/kg

Magrolimab 30 mg/kg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Active Control

Group I: Safety Run-in Cohort 2, Magrolimab + DocetaxelExperimental Treatment2 Interventions

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 * 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.

Group II: Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + PlatinumExperimental Treatment5 Interventions

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 * 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.

Group III: Pre-expansion Safety Run-in Cohort, Magrolimab + PembrolizumabExperimental Treatment2 Interventions

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.

Group IV: Phase 2 Cohort 3, Magrolimab + DocetaxelExperimental Treatment2 Interventions

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.

Group V: Phase 2 Cohort 2, Magrolimab + PembrolizumabExperimental Treatment2 Interventions

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.

Group VI: Phase 2 Cohort 1, Magrolimab + Zimberelimab + 5-FU + Platinum (Arm C)Experimental Treatment5 Interventions

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.

Group VII: Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum (Arm A)Experimental Treatment5 Interventions

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.

Group VIII: Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum (Arm B)Active Control4 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

5-FU

2014

Completed Phase 3

~3100

Cisplatin

2013

Completed Phase 3

~3120

Carboplatin

2014

Completed Phase 3

~6120

Zimberelimab

2020

Completed Phase 2

~230

Magrolimab

2022

Completed Phase 2

~220

Pembrolizumab

2017

Completed Phase 3

~2810

Docetaxel

1995

Completed Phase 4

~6550

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include immune checkpoint inhibitors like pembrolizumab and nivolumab, which target the PD-1/PD-L1 pathway to boost the immune system's ability to attack cancer cells. Cetuximab, another treatment, targets the epidermal growth factor receptor (EGFR) to inhibit tumor growth and proliferation. Magrolimab, an anti-CD47 monoclonal antibody, blocks the 'don't eat me' signal on cancer cells, promoting their phagocytosis by immune cells. These mechanisms are vital for HNSCC patients as they provide targeted strategies to disrupt cancer cell survival and enhance the body's immune response against tumors.

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies.