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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04854499




Registration number
NCT04854499
Ethics application status
Date submitted
19/04/2021
Date registered
22/04/2021

Titles & IDs
Public title
Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
Scientific title
A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
Secondary ID [1] 0 0
2020-005708-20
Secondary ID [2] 0 0
GS-US-548-5916
Universal Trial Number (UTN)
Trial acronym
ELEVATE HNSCC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - 5-FU
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Zimberelimab

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.

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.

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.

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.

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.


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: Pembrolizumab
Administered intravenously

Treatment: Drugs: Docetaxel
Administered intravenously

Treatment: Drugs: 5-FU
Administered intravenously

Treatment: Drugs: Cisplatin
Administered intravenously

Treatment: Drugs: Carboplatin
Administered intravenously

Treatment: Drugs: Zimberelimab
Administered intravenously

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
First Dose up to 21 days
Primary outcome [2] 0 0
Phase 2 Cohorts 1: Progression-free Survival (PFS)
Timepoint [2] 0 0
Up to 5 years
Primary outcome [3] 0 0
Phase 2 Cohorts 2 and 3: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to 9 months
Secondary outcome [1] 0 0
Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab
Timepoint [1] 0 0
Up to end of treatment (approximately 24 months)
Secondary outcome [2] 0 0
Safety Run-In and Phase 2 Cohorts: Percentage of Participants who Developed Antidrug Antibodies (ADAs) to Magrolimab
Timepoint [2] 0 0
Up to end of treatment (approximately 24 months)
Secondary outcome [3] 0 0
Phase 2 Cohorts: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to 9 months
Secondary outcome [4] 0 0
Phase 2 Cohorts: Progression-free Survival (PFS)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Phase 2 Cohorts: Duration of Response (DOR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Phase 2 Cohorts: Overall Survival (OS)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline; up to 24 months
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
Baseline; up to 24 months
Secondary outcome [9] 0 0
Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)
Timepoint [9] 0 0
Baseline; up to 24 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Macquarie University - Macquarie Park
Recruitment hospital [3] 0 0
Blacktown Hospital - Westmead
Recruitment hospital [4] 0 0
Cairns Hospital - Cairns
Recruitment hospital [5] 0 0
University of the Sunshine Coast - Sippy Downs
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Austin Health - Heidelberg
Recruitment hospital [8] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4870 - Cairns
Recruitment postcode(s) [5] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
South Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Belgium
State/province [17] 0 0
Antwerpen
Country [18] 0 0
Belgium
State/province [18] 0 0
Brasschaat
Country [19] 0 0
Belgium
State/province [19] 0 0
Edegem
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
Country [21] 0 0
Belgium
State/province [21] 0 0
Libramont-Chevigny
Country [22] 0 0
Belgium
State/province [22] 0 0
Mechelen
Country [23] 0 0
Belgium
State/province [23] 0 0
Namur
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux
Country [25] 0 0
France
State/province [25] 0 0
Dijon
Country [26] 0 0
France
State/province [26] 0 0
Lyon
Country [27] 0 0
France
State/province [27] 0 0
Marseille
Country [28] 0 0
France
State/province [28] 0 0
Nice
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Pierre-benite
Country [31] 0 0
France
State/province [31] 0 0
Suresnes
Country [32] 0 0
France
State/province [32] 0 0
Villejuif
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Bonn
Country [35] 0 0
Germany
State/province [35] 0 0
GÃttingen
Country [36] 0 0
Germany
State/province [36] 0 0
Hamburg
Country [37] 0 0
Germany
State/province [37] 0 0
Leipzig
Country [38] 0 0
Germany
State/province [38] 0 0
Munich
Country [39] 0 0
Hong Kong
State/province [39] 0 0
Hong Kong
Country [40] 0 0
Hong Kong
State/province [40] 0 0
Lai Chi Kok
Country [41] 0 0
Italy
State/province [41] 0 0
Bologna
Country [42] 0 0
Italy
State/province [42] 0 0
Brescia
Country [43] 0 0
Italy
State/province [43] 0 0
Lucca
Country [44] 0 0
Italy
State/province [44] 0 0
Milan
Country [45] 0 0
Italy
State/province [45] 0 0
Modena
Country [46] 0 0
Italy
State/province [46] 0 0
Reggio Emilia
Country [47] 0 0
Italy
State/province [47] 0 0
Siena
Country [48] 0 0
Poland
State/province [48] 0 0
Bydgoszcz
Country [49] 0 0
Poland
State/province [49] 0 0
Gliwice
Country [50] 0 0
Poland
State/province [50] 0 0
Poznan
Country [51] 0 0
Poland
State/province [51] 0 0
Siedlce
Country [52] 0 0
Poland
State/province [52] 0 0
Warsaw
Country [53] 0 0
Portugal
State/province [53] 0 0
Braga
Country [54] 0 0
Portugal
State/province [54] 0 0
Faro
Country [55] 0 0
Portugal
State/province [55] 0 0
Lisboa
Country [56] 0 0
Portugal
State/province [56] 0 0
Matosinhos
Country [57] 0 0
Portugal
State/province [57] 0 0
Porto
Country [58] 0 0
Spain
State/province [58] 0 0
Barcelona
Country [59] 0 0
Spain
State/province [59] 0 0
Jaen
Country [60] 0 0
Spain
State/province [60] 0 0
Madrid
Country [61] 0 0
Spain
State/province [61] 0 0
Malaga
Country [62] 0 0
Spain
State/province [62] 0 0
Pamplona
Country [63] 0 0
Spain
State/province [63] 0 0
Sevilla
Country [64] 0 0
Spain
State/province [64] 0 0
Valencia
Country [65] 0 0
United Kingdom
State/province [65] 0 0
London
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.