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

NCT ID: NCT04854499

Last Updated: 2025-11-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

193 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-07

Study Completion Date

2024-10-02

Brief Summary

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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).

Detailed Description

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Conditions

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Head and Neck Squamous Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Pembrolizumab

Intervention Type DRUG

Administered intravenously

5-FU

Intervention Type DRUG

Administered intravenously

Cisplatin

Intervention Type DRUG

Administered intravenously

Carboplatin

Intervention Type DRUG

Administered intravenously

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.

Group Type ACTIVE_COMPARATOR

5-FU

Intervention Type DRUG

Administered intravenously

Cisplatin

Intervention Type DRUG

Administered intravenously

Carboplatin

Intervention Type DRUG

Administered intravenously

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.

Group Type ACTIVE_COMPARATOR

Magrolimab

Intervention Type DRUG

Administered intravenously

5-FU

Intervention Type DRUG

Administered intravenously

Cisplatin

Intervention Type DRUG

Administered intravenously

Carboplatin

Intervention Type DRUG

Administered intravenously

Zimberelimab

Intervention Type DRUG

Administered intravenously

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Pembrolizumab

Intervention Type DRUG

Administered intravenously

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Docetaxel

Intervention Type DRUG

Administered intravenously

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Pembrolizumab

Intervention Type DRUG

Administered intravenously

5-FU

Intervention Type DRUG

Administered intravenously

Cisplatin

Intervention Type DRUG

Administered intravenously

Carboplatin

Intervention Type DRUG

Administered intravenously

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Docetaxel

Intervention Type DRUG

Administered intravenously

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Pembrolizumab

Intervention Type DRUG

Administered intravenously

Interventions

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Magrolimab

Administered intravenously

Intervention Type DRUG

Pembrolizumab

Administered intravenously

Intervention Type DRUG

Docetaxel

Administered intravenously

Intervention Type DRUG

5-FU

Administered intravenously

Intervention Type DRUG

Cisplatin

Administered intravenously

Intervention Type DRUG

Carboplatin

Administered intravenously

Intervention Type DRUG

Zimberelimab

Administered intravenously

Intervention Type DRUG

Other Intervention Names

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GS-4721 KEYTRUDA®

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed metastatic or locally recurrent HNSCC that is considered incurable by local therapies.

Safety Run-in Cohort 1 and Phase 2 Cohorts 1

* Should not have had prior systemic therapy administered in the recurrent or metastatic setting.
* Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx. Nasopharynx is not included.

Safety Run-in Cohort 2 and Phase 2 Cohort 3

* Histologically or cytologically confirmed locally advanced/mHNSCC regardless of PD-L1 status with at least 1 and no more than 2 lines of prior systemic anticancer therapy in the locally advanced/metastatic setting.

Exclusion Criteria

* Active central nervous system (CNS) disease (individuals with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active).
* History of (noninfectious) pneumonitis that required steroids or current pneumonitis.
* Progressive disease within 6 months of completion of curatively intended treatment for locally advanced/mHNSCC.

Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2

* 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.

Safety Run-in Cohort 2 and Phase 2 Cohort 3

* Prior treatment with a taxane.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Ironwood Cancer and Research Center

Chandler, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

UCLA Hematology/Oncology

Los Angeles, California, United States

Site Status

Stanford Cancer Institute

Palo Alto, California, United States

Site Status

Torrance Memorial Physician Network - Cancer Care Associates

Redondo Beach, California, United States

Site Status

Providence Medical Foundation

Santa Rosa, California, United States

Site Status

Memorial Healthcare System

Hollywood, Florida, United States

Site Status

Ocala Oncology Center

Ocala, Florida, United States

Site Status

University Center and Blood Center,LLC.

Athens, Georgia, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Virginia Piper Cancer Center (Alliant Health

Minneapolis, Minnesota, United States

Site Status

Washington University of Medicine- Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Astera Cancer Care

East Brunswick, New Jersey, United States

Site Status

Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital

New York, New York, United States

Site Status

New York Cancer and Blood Specialists

Port Jefferson Station, New York, United States

Site Status

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Macquarie University

Macquarie Park, New South Wales, Australia

Site Status

Blacktown Hospital

Westmead, New South Wales, Australia

Site Status

Cairns Hospital

Cairns, Queensland, Australia

Site Status

University of the Sunshine Coast

Sippy Downs, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Alfred Health

Melbourne, Victoria, Australia

Site Status

ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg

Antwerp, , Belgium

Site Status

Algemeen Ziekenhuis Klina

Brasschaat, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Universitaire Ziekenhuis Leuven

Leuven, , Belgium

Site Status

Centre Hospitalizer De L'Ardenne

Libramont-Chevigny, , Belgium

Site Status

AZ Sint-Maarten

Mechelen, , Belgium

Site Status

CHU UCL Namur - Sainte-Elisabeth

Namur, , Belgium

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Hopital de la Timone

Marseille, , France

Site Status

Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site Est

Nice, , France

Site Status

Institut Curie

Paris, , France

Site Status

Hopital Pitie-Salpetriere

Paris, , France

Site Status

Civils de Lyon-Centre Hopitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Hopital Foch

Suresnes, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Charite University Medicine

Berlin, , Germany

Site Status

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III

Bonn, , Germany

Site Status

Universitatsmedizin Gottingen

GÃttingen, , Germany

Site Status

Kath. Marienkrankenhaus gGmbH

Hamburg, , Germany

Site Status

Universitäres Krebszentrum Leipzig

Leipzig, , Germany

Site Status

Technische Universitat Munchen (TUM) - Klinikum Rechts der Isar

Munich, , Germany

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Princess Margaret Hospital

Lai Chi Kok, , Hong Kong

Site Status

Azienda Ospedaliero - Universitaria di Bologna - IRCCS

Bologna, , Italy

Site Status

ASST degli Spedali Civili di Brescia

Brescia, , Italy

Site Status

Ospedale San Luca Luca

Lucca, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale Tumori Milano

Milan, , Italy

Site Status

Azienda Ospedaliero-Universitaria di Modena - Policlinico

Modena, , Italy

Site Status

Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status

Azienda Ospedaliero - Universitaria Senese

Siena, , Italy

Site Status

Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

Bydgoszcz, , Poland

Site Status

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie, Panstwowy Instytut Badawczy, Oddzial x Gliwicach

Gliwice, , Poland

Site Status

Wielkopolskie Centrum Onkologii im. Marii Sklodowskiej-Curie, Oddzial Onkologii Klinicznej i Immunookologii z Poddoddzialem Dziennym i Izba Przyjec

Poznan, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny w Siedlcach

Siedlce, , Poland

Site Status

Narodowy Instytut Onkologii im. M. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Glowy i Szyi

Warsaw, , Poland

Site Status

Hospital de Braga

Braga, , Portugal

Site Status

Centro Hospitalar do Algarve

Faro, , Portugal

Site Status

Hospital CUF Descobertas

Lisbon, , Portugal

Site Status

Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SA

Matosinhos Municipality, , Portugal

Site Status

Centro Hospitalar Universitario do Porto

Porto, , Portugal

Site Status

Instituto Portugues de Oncologia Do Porto Francisco Gentil,E.P.E.

Porto, , Portugal

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital De La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario de Jaen

Jaén, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

MD Anderson Cancer Center

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Royal Marsden NHS Foundation Trust, Royal Marsden - Sutton

London, , United Kingdom

Site Status

Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Countries

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United States Australia Belgium France Germany Hong Kong Italy Poland Portugal Spain United Kingdom

References

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Colevas AD, Dinis J, Chin V, Costa DA, Park JJ, Fang B, et al. A Phase 2 Study of Magrolimab Combination Therapy in Patients with Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma (ELEVATE HNSCC) [Poster TPS6102]. American Society for Clinical Oncology (ASCO); 2023 June 2-6; Chicago, IL.

Reference Type BACKGROUND

Colevas AD, Dinis J, Chin V, Costa DA, Park JJ, Fang B, et al. A phase 2 study of magrolimab combination therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (ELEVATE HNSCC) [Abstract]. American Society for Clinical Oncology (ASCO); 2023 June 2-6; Chicago, IL.

Reference Type BACKGROUND

Colevas AD, Kerrigan K, Chin V, Rainey N, Park J, Fang B, et al. Safety and Tolerability of Magrolimab Combination Therapy in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM-HNSCC) [Poster #675]. SITC: 38th Society for Immunotherapy of Cancer Annual Meeting; 2023 November 3-5, 2023; San Diego, CA.

Reference Type BACKGROUND

Colevas AD, Kerrigan K, Chin V, Rainey N, Park J, Fang B, et al. Safety and tolerability of magrolimab combination therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC) [Abstract]. SITC: 38th Society for Immunotherapy of Cancer Annual Meeting; 2023 November 3-5, 2023; San Diego, CA.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2020-005708-20

Identifier Type: OTHER

Identifier Source: secondary_id

GS-US-548-5916

Identifier Type: -

Identifier Source: org_study_id

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