Clinical Trial: NCT04854499 - My Cancer Genome

NCT04854499

Description:

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).

Related Conditions:

Head and Neck Squamous Cell Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04854499

Trial Eligibility

Document

Title

Brief Title: Study of Magrolimab Combination Therapy in Participants 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

Clinical Trial IDs

ORG STUDY ID: GS-US-548-5916
SECONDARY ID: 2020-005708-20
NCT ID: NCT04854499

Conditions

Head and Neck Squamous Cell Carcinoma

Interventions

Drug	Synonyms	Arms
Magrolimab	GS-4721	Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Pembrolizumab		Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Docetaxel		Phase 2 Cohort 3, Magrolimab + Docetaxel
5-FU		Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Cisplatin		Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum
Carboplatin		Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum

Purpose

Trial Arms

Name	Type	Description	Interventions
Safety Run-in Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum	Experimental	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.	Magrolimab Pembrolizumab 5-FU Cisplatin Carboplatin
Safety Run-in Cohort 2, Magrolimab + Docetaxel	Experimental	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.	Magrolimab Docetaxel
Pre-expansion Safety Run-in Cohort, Magrolimab + Pembrolizumab	Experimental	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.	Magrolimab Pembrolizumab
Phase 2 Cohort 1, Magrolimab + Pembrolizumab + 5-FU + Platinum	Experimental	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.	Magrolimab Pembrolizumab 5-FU Cisplatin Carboplatin
Phase 2 Cohort 1, Pembrolizumab + 5-FU + Platinum	Experimental	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.	Pembrolizumab 5-FU Cisplatin Carboplatin
Phase 2 Cohort 2, Magrolimab + Pembrolizumab	Experimental	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.	Magrolimab Pembrolizumab
Phase 2 Cohort 3, Magrolimab + Docetaxel	Experimental	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.	Magrolimab Docetaxel

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

          -  HNSCC per protocol specified inclusion criteria regardless of PD-L1 status

          -  HNSCC per protocol specified inclusion criterion with a PD-L1 CPS ≥ 1

        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

               -  5-FU and platinum-based chemotherapy (Safety Run-in Cohort 1 and Phase 2 Cohorts
                  1 only)

        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.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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
Safety Issue:
Description:	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.

Secondary Outcome Measures

Measure:	Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab
Time Frame:	Up to end of treatment (approximately 24 months)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	Phase 2 Cohorts: Objective Response Rate (ORR)
Time Frame:	Up to 9 months
Safety Issue:
Description:	ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as determined by independent central review.

Measure:	Phase 2 Cohorts: Progression-free survival (PFS)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	Phase 2 Cohorts: Duration of Response (DOR)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	Phase 2 Cohorts: Overall Survival (OS)
Time Frame:	Up to 5 years
Safety Issue:
Description:	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.

Measure:	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
Safety Issue:
Description:	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).

Measure:	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
Safety Issue:
Description:	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.

Measure:	Phase 2 Cohorts: Change From Baseline in the 5-level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)
Time Frame:	Baseline; up to 24 months
Safety Issue:
Description:	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.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Gilead Sciences

Last Updated

July 2, 2021

Clinical Trials /

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