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

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04854499

Collaborator

(none)

230

Enrollment

Locations

Arms

23.8

Anticipated Duration (Months)

7.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Sep 7, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: GS-4721 Drug: Docetaxel Administered intravenously

Outcome Measures

Primary Outcome Measures

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 [First Dose up to 21 days]
Phase 2 Cohorts 1: Progression-free survival (PFS) [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) [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

Safety Run-In and Phase 2 Cohorts: Serum Concentration of Magrolimab [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 [Up to end of treatment (approximately 24 months)]
Phase 2 Cohorts: Objective Response Rate (ORR) [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) [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) [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) [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 [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) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer and Research Center	Chandler	Arizona	United States	85224
2	City of Hope	Duarte	California	United States	91010
3	UCLA Hematology/Oncology	Los Angeles	California	United States	90095
4	Stanford Cancer Institute	Palo Alto	California	United States	94305
5	Providence Medical Foundation	Santa Rosa	California	United States	95403
6	University Center and Blood Center,LLC.	Athens	Georgia	United States	30607
7	Virginia Piper Cancer Center (Alliant Health	Minneapolis	Minnesota	United States	55407
8	Washington University of Medicine- Siteman Cancer Center	Saint Louis	Missouri	United States	63110
9	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
10	Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital	New York	New York	United States	10029
11	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
12	Oregon Health and Science University	Portland	Oregon	United States	97239
13	MD Anderson Cancer Center	Houston	Texas	United States	77030
14	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
15	St. Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
16	Macquarie University	Macquarie Park	New South Wales	Australia	2109
17	Blacktown Hospital	Westmead	New South Wales	Australia	2145
18	Cairns Hospital	Cairns	Queensland	Australia	4870
19	University of the Sunshine Coast	Sippy Downs	Queensland	Australia	4556
20	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
21	Hong Kong United Oncology Centre	Hong Kong		Hong Kong
22	Queen Mary Hospital	Hong Kong		Hong Kong
23	Hong Kong Sanatorium and Hospital	Wan Chai		Hong Kong	999077
24	Hospital de Braga	Braga		Portugal	4710-243
25	Hospital CUF Descobertas	Lisboa		Portugal	1998-018
26	Unidade Local de Saude de Matosinhos EPE - Hospital Pedro Hispano SA	Matosinhos		Portugal	4464-513
27	Instituto Portugues de Oncologia Do Porto Francisco Gentil,E.P.E.	Porto		Portugal	4200-072
28	Hospital De La Santa Creu I Sant Pau	Barcelona		Spain	8041
29	Hospital Universitario La Paz	Madrid		Spain	28046
30	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
31	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
32	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026