Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma (ELEVATE HNSCC)

March 7, 2024 updated by: Gilead Sciences

A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma

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 patients with head and neck squamous cell carcinoma (HNSCC).

Study Overview

Study Type

Interventional

Enrollment (Estimated)

230

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St. Vincent's Hospital Sydney
      • Macquarie Park, New South Wales, Australia, 2109
        • Macquarie University
      • Westmead, New South Wales, Australia, 2145
        • Blacktown Hospital
    • Queensland
      • Cairns, Queensland, Australia, 4870
        • Cairns Hospital
      • Sippy Downs, Queensland, Australia, 4556
        • University of the Sunshine Coast
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
      • Melbourne, Victoria, Australia, 3004
        • Alfred Health
      • Antwerpen, Belgium, 2020
        • ZiekenhuisNetwerk Antwerpen (ZNA) - Stuivenberg
      • Brasschaat, Belgium, 2930
        • Algemeen Ziekenhuis Klina
      • Edegem, Belgium, 2650
        • UZ Antwerpen
      • Leuven, Belgium, 3000
        • Universitaire Ziekenhuis Leuven
      • Libramont-Chevigny, Belgium, 6800
        • Centre Hospitalizer De L'Ardenne
      • Mechelen, Belgium, 2800
        • Az Sint-Maarten
      • Namur, Belgium, 5000
        • CHU UCL Namur - Sainte-Elisabeth
      • Bordeaux, France, 33000
        • Institut Bergonié
      • Dijon, France, 21079
        • Centre Georges François Leclerc
      • Lyon, France, 69373
        • Centre Léon Berard
      • Marseille, France, 13005
        • Hopital de La Timone
      • Nice, France, 6189
        • Centre de Lutte Contre le Cancer (CLCC) - Centre Antoine Lacassagne (CAL) - Site Est
      • Paris, France, 75005
        • Institut Curie
      • Paris, France, 75013
        • Hôpital Pitié-Salpétrière
      • Pierre-benite, France, 69310
        • Civils de Lyon-Centre Hopitalier Lyon Sud
      • Suresnes, France, 92151
        • Hopital Foch
      • Villejuif, France, 94805
        • Institut Gustave Roussy
      • Berlin, Germany, 10177
        • Charite University Medicine
      • Bonn, Germany, 53127
        • Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III
      • GÃttingen, Germany, 37075
        • Universitatsmedizin Gottingen
      • Hamburg, Germany, 22087
        • Kath. Marienkrankenhaus gGmbH
      • Leipzig, Germany, 4103
        • Universitäres Krebszentrum Leipzig
      • Munich, Germany, 81675
        • Technische Universitat Munchen (TUM) - Klinikum Rechts der Isar
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Lai Chi Kok, Hong Kong
        • Princess Margaret Hospital
      • Bologna, Italy, 40138
        • Azienda Ospedaliero - Universitaria di Bologna - IRCCS
      • Brescia, Italy, 25123
        • Asst Degli Spedali Civili Di Brescia
      • Lucca, Italy, 55100
        • Ospedale San Luca Luca
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori Milano
      • Modena, Italy, 41124
        • Azienda Ospedaliero-Universitaria di Modena - Policlinico
      • Reggio Emilia, Italy, 42100
        • Arcispedale Santa Maria Nuova
      • Siena, Italy, 53100
        • Azienda Ospedaliero - Universitaria Senese
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
      • Gliwice, Poland, 44-102
        • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie, Panstwowy Instytut Badawczy, Oddzial x Gliwicach
      • Poznan, Poland, 61-866
        • Wielkopolskie Centrum Onkologii im. Marii Sklodowskiej-Curie, Oddzial Onkologii Klinicznej i Immunookologii z Poddoddzialem Dziennym i Izba Przyjec
      • Siedlce, Poland, 08-110
        • Wojewodzki Szpital Specjalistyczny w Siedlcach
      • Warsaw, Poland, 2781
        • Narodowy Instytut Onkologii im. M. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Glowy i Szyi
      • Braga, Portugal, 4710-243
        • Hospital de Braga
      • Faro, Portugal, 8000-366
        • Centro Hospitalar do Algarve
      • Lisboa, Portugal, 1998-018
        • Hospital CUF Descobertas
      • Matosinhos, Portugal, 4464-513
        • Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SA
      • Porto, Portugal, 4050-011
        • Centro Hospitalar Universitario do Porto
      • Porto, Portugal, 4200-072
        • Instituto Portugues de Oncologia Do Porto Francisco Gentil,E.P.E.
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 8041
        • Hospital de La Santa Creu i Sant Pau
      • Barcelona, Spain, 8003
        • Hospital del Mar
      • Jaen, Spain, 23007
        • Hospital Universitario de Jaén
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Malaga, Spain, 29010
        • Hospital Regional Universitario de Málaga
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
      • Valencia, Spain
        • Hospital Clinico Universitario de Valencia
      • London, United Kingdom, SM2 5PT
        • Royal Marsden NHS Foundation Trust, Royal Marsden - Sutton
      • Taunton, United Kingdom, TA1 5DA
        • Musgrove Park Hospital
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer and Research Center
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • Los Angeles, California, United States, 90095
        • UCLA Hematology/Oncology
      • Palo Alto, California, United States, 94305
        • Stanford Cancer Institute
      • Redondo Beach, California, United States, 90277
        • Torrance Memorial Physician Network - Cancer Care Associates
      • Santa Rosa, California, United States, 95403
        • Providence Medical Foundation
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Healthcare System
      • Ocala, Florida, United States, 34471
        • Ocala Oncology Center
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Center and Blood Center,LLC.
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Virginia Piper Cancer Center (Alliant Health
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University of Medicine- Siteman Cancer Center
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Astera Cancer Care
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital
      • Port Jefferson Station, New York, United States, 11776
        • New York Cancer and Blood Specialists
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • OU Health Stephenson Cancer Center
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17602
        • Lancaster General Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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.

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
  • 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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Administered intravenously
Other Names:
  • KEYTRUDA®
Administered intravenously
Administered intravenously
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
  • 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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Other Names:
  • KEYTRUDA®
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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Administered intravenously
Other Names:
  • KEYTRUDA®
Administered intravenously
Administered intravenously
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.

Administered intravenously
Administered intravenously
Other Names:
  • KEYTRUDA®
Administered intravenously
Administered intravenously
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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Other Names:
  • KEYTRUDA®
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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Experimental: 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.

Administered intravenously
Other Names:
  • GS-4721
Administered intravenously
Administered intravenously
Administered intravenously
Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Run-in Cohorts: 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 up to 21 days
First Dose up to 21 days
Phase 2 Cohorts 2 and 3: Objective Response Rate (ORR)
Time Frame: Up to 9 months
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as determined by investigator assessment.
Up to 9 months
Phase 2 Cohorts 1: Progression-free Survival (PFS)
Time Frame: Up to 5 years
PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as assessed by investigator assessment, or death from any cause, whichever occurs first.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab
Time Frame: Up to end of treatment (approximately 24 months)
Up to end of treatment (approximately 24 months)
Safety Run-In and Phase 2 Cohorts: Percentage of Participants who Developed Antidrug Antibodies (ADAs) to Magrolimab
Time Frame: Up to end of treatment (approximately 24 months)
Up to end of treatment (approximately 24 months)
Phase 2 Cohorts: Duration of Response (DOR)
Time Frame: Up to 5 years
DOR is defined as the time from first documentation of CR or PR to the earliest date of documented disease progression or death from any cause, whichever occurs first.
Up to 5 years
Phase 2 Cohorts: Overall Survival (OS)
Time Frame: Up to 5 years
OS is defined as the time from the date of randomization (Phase 2 Cohorts 1) or time from the date of dose initiation (Phase 2 Cohorts 2 and 3) to death from any cause.
Up to 5 years
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
Time Frame: Baseline; up to 24 months
The EORTC QLQ-C30 questionnaire is a specific questionnaire for cancer, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).
Baseline; up to 24 months
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)
Time Frame: Baseline; up to 24 months
The head & neck cancer module is a 35-item questionnaire designed for use among a wide range of participants with head & neck cancer, varying in disease stage and treatment modality. It includes 7 multi-item scales that assess pain (4 items), swallowing (4 items), senses (2 items), speech (3 items), social eating (4 items), social contact (5 items), and sexuality (2 items). There are also 11 single items. Using a 4-point Likert scale, participants indicate the degree to which they have experienced symptoms. For all items and scales, high scores indicate more problems.
Baseline; up to 24 months
Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)
Time Frame: Baseline; up to 24 months

The EQ-5D-5L is a standard measure of health-related quality of life. The tool consists of the EQ-5D-5L descriptive part and the EQ visual analogue scale (VAS). The descriptive part comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each of these 5 dimensions has 5 levels (no problem, slight problems, moderate problems, severe problems, and extreme problems). Results for each of the 5 dimensions are combined into a 5-digit number to describe the participant's health state.

The EQ-VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating "the worst health you can imagine" and 100 indicating "the best health you can imagine." Higher scores of EQ VAS indicate better health.

Baseline; up to 24 months
Phase 2 Cohorts: Objective Response Rate (ORR)
Time Frame: Up to 9 months
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as determined by investigator assessment.
Up to 9 months
Phase 2 Cohorts: Progression-free Survival (PFS)
Time Frame: Up to 5 years
PFS is defined as the time from the date of randomization (Phase 2 Cohorts 1) or date of dose initiation (Phase 2 Cohorts 2 and 3) until the earliest date of documented disease progression as determined by investigator assessment per RECIST, version 1.1, or death from any cause, whichever occurs first.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2021

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

April 19, 2021

First Submitted That Met QC Criteria

April 19, 2021

First Posted (Actual)

April 22, 2021

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Squamous Cell Carcinoma

Clinical Trials on Magrolimab

3
Subscribe