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

• ClinicalTrials.gov Identifier: NCT04854499
• Recruitment Status: Active, not recruiting
• First Posted: April 22, 2021
• Last Update Posted: April 11, 2024
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: April 19, 2021
• First Posted Date: April 22, 2021
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: September 7, 2021
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 22, 2024)

• 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 ]
• 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.
• 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.

Original Primary Outcome Measures (submitted: April 19, 2021)

• 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 ]
• 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.
• 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.

Current Secondary Outcome Measures (submitted: January 22, 2024)

• Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab [ Time Frame: 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) ]
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• 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.

Original Secondary Outcome Measures (submitted: April 19, 2021)

• Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab [ Time Frame: 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) ]
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
• Official Title: A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Squamous Cell Carcinoma

Intervention

• Drug: Magrolimab
  Administered intravenously
  Other Name: GS-4721
• Drug: Pembrolizumab
  Administered intravenously
  Other Name: KEYTRUDA®
• Drug: Docetaxel
  Administered intravenously
• Drug: 5-FU
  Administered intravenously
• Drug: Cisplatin
  Administered intravenously
• Drug: Carboplatin
  Administered intravenously
• Drug: Zimberelimab
  Administered intravenously

Study Arms

• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Pembrolizumab
  • Drug: 5-FU
  • Drug: Cisplatin
  • Drug: Carboplatin
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Docetaxel
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Pembrolizumab
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Pembrolizumab
  • Drug: 5-FU
  • Drug: Cisplatin
  • Drug: Carboplatin
• 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.

  Interventions:

  • Drug: Pembrolizumab
  • Drug: 5-FU
  • Drug: Cisplatin
  • Drug: Carboplatin
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: 5-FU
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Zimberelimab
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Pembrolizumab
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 24, 2022): 230
• Original Estimated Enrollment (submitted: April 19, 2021): 233
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility 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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Germany, Hong Kong, Italy, Poland, Portugal, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04854499
• Other Study ID Numbers: GS-US-548-5916; 2020-005708-20 ( Other Identifier: European Medicines Agency )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: April 2024