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

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ClinicalTrials.gov Identifier: NCT04854499
Recruitment Status : Recruiting
First Posted : April 22, 2021
Last Update Posted : September 21, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

The study consists of Safety Run-in and Phase 2 Cohorts.

The primary objectives of the safety run-in cohorts of this study are to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with pembrolizumab + 5-fluorouracil (5-FU) + platinum chemotherapy, and docetaxel in combination with magrolimab in participants with head and neck squamous cell carcinoma (HNSCC).

Phase 2 Cohorts 1: To evaluate the progression-free survival (PFS) with magrolimab in combination with pembrolizumab + 5-FU + platinum versus pembrolizumab + 5-FU + platinum as assessed by independent central review.

Phase 2 Cohorts 2 and 3: To evaluate the efficacy of magrolimab in combination with pembrolizumab and magrolimab in combination with docetaxel as determined by the investigator-assessed objective response rate (ORR).


Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Magrolimab Drug: Pembrolizumab Drug: Docetaxel Drug: 5-FU Drug: Cisplatin Drug: Carboplatin Drug: Zimberelimab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : September 7, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Pembrolizumab
Administered intravenously

Drug: 5-FU
Administered intravenously

Drug: Cisplatin
Administered intravenously

Drug: Carboplatin
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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Docetaxel
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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Pembrolizumab
Administered intravenously

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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Pembrolizumab
Administered intravenously

Drug: 5-FU
Administered intravenously

Drug: Cisplatin
Administered intravenously

Drug: Carboplatin
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.

Drug: Pembrolizumab
Administered intravenously

Drug: 5-FU
Administered intravenously

Drug: Cisplatin
Administered intravenously

Drug: Carboplatin
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 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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: 5-FU
Administered intravenously

Drug: Cisplatin
Administered intravenously

Drug: Carboplatin
Administered intravenously

Drug: Zimberelimab
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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Pembrolizumab
Administered intravenously

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.

Drug: Magrolimab
Administered intravenously
Other Name: GS-4721

Drug: Docetaxel
Administered intravenously




Primary Outcome Measures :
  1. 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 ]
  2. 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 independent central review, or death from any cause, whichever occurs first.

  3. 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.


Secondary Outcome Measures :
  1. Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab [ Time Frame: Up to end of treatment (approximately 24 months) ]
  2. 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) ]
  3. 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 independent central review.

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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.

  9. 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

  • Progressive disease within 6 months of completion of curatively intended systemic treatment for locally advanced/mHNSCC
  • Prior treatment with a taxane

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04854499


Contacts
Layout table for location contacts
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations
Show Show 37 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
Additional Information:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04854499    
Other Study ID Numbers: GS-US-548-5916
2020-005708-20 ( EudraCT Number )
First Posted: April 22, 2021    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cisplatin
Carboplatin
Docetaxel
Pembrolizumab
Magrolimab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological