Clinical Trials Register

Summary
EudraCT Number:	2020-005265-14
Sponsor's Protocol Code Number:	GS-US-548-5918
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-12-13
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-005265-14

A.3

Full title of the trial

A Phase 2 Multi-Arm Study of Magrolimab in Patients with Solid Tumors

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to investigate safety and efficacy of magrolimab in different solid tumours.

A.4.1

Sponsor's protocol code number

GS-US-548-5918

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Gilead Sciences, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences International Ltd.
B.5.2	Functional name of contact point	Clinical Trials Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, Granta Park
B.5.3.2	Town/ city	Abington, Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441223897284
B.5.6	E-mail	clinical.trials@gilead.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Magrolimab
D.3.2	Product code	GS-4721
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Magrolimab
D.3.9.2	Current sponsor code	GS-4721
D.3.9.3	Other descriptive name	Hu5F9-G4
D.3.9.4	EV Substance Code	SUB194348
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Docetaxel Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare S.L.U. D.2.1.1.3
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Docetaxel
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Docetaxel
D.3.9.3	Other descriptive name	Docetaxel
D.3.9.4	EV Substance Code	SUB12492MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Solid tumours including metastatic non-small cell lung cancer [mNSCLC], metastatic urothelial cancer [mUC], and metastatic small cell lung cancer [mSCLC]

E.1.1.1

Medical condition in easily understood language

Solid tumours including lung, and urothelial cancer.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10059515
E.1.2	Term	Non-small cell lung cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10046725
E.1.2	Term	Urothelial carcinoma ureter metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10046730
E.1.2	Term	Urothelial carcinoma urethra metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10059514
E.1.2	Term	Small cell lung cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety, tolerability, and recommended Phase 2 dose of magrolimab + docetaxel combination therapy in solid tumors (Safety Run-in Cohort 1, Phase 2 Cohorts 1a, 1b, and 1c).
To evaluate the efficacy of magrolimab + docetaxel combination therapy in solid tumors as determined by investigator-assessed objective response rate (ORR) (Phase 2 Cohorts 1a, 1b, and 1c).

E.2.2

Secondary objectives of the trial

To evaluate progression-free survival (PFS) by investigator assessment (Phase 2 Cohorts 1a, 1b, and 1c)
To evaluate additional measures of efficacy of magrolimab + docetaxel combination therapy, including duration of response (DOR) and overall survival (OS) (Phase 2 Cohorts 1a, 1b, and 1c)
To evaluate the pharmacokinetics (PK) and immunogenicity of magrolimab when given with docetaxel as a combination therapy (Safety Run-in Cohort 1, Phase 2 Cohorts 1a, 1b, and 1c)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Patient has provided informed consent
2) Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol
3) Male or female, ≥ 18 years of age
4) Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
5) Laboratory measurements, blood counts:
a) Hemoglobin ≥ 9.5 g/dL. Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits set per exclusion criterion 4
b) Absolute neutrophil count ≥ 1.5x10^9
c) Platelets ≥ 100x10^9
6) Laboratory measurements, renal function:
a) Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular filtration rate > 40 mL/min/1.73m²
7) Adequate liver function, as demonstrated by:
a) Aspartate aminotransferase ≤ 1.5 x ULN
b) Alanine aminotransferase ≤ 1.5 x ULN
c) Bilirubin ≤ 1.25 x ULN, or ≤ 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
8) Pretreatment blood cross-match completed
9) Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 5 of protocol
10) Measurable disease according to RECIST, Version 1.1. Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
11) Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate). A newly
obtained biopsy (within 90 days prior to study treatment start) is strongly preferred, but an archival sample is acceptable if obtained within 6 months prior to enrollment. Patients will also be requested to consent to a mandatory on-treatment tumor biopsy unless not feasible as determined by the investigator and discussed with the sponsor.
14) Safety Run-in Cohort 1: Patients with metastatic advanced solid tumors who have had at least 1 prior line of systemic anticancer therapy (mNSCLC and mSCLC) in a locally advanced/metastatic setting, or 2 prior lines of systemic anticancer therapy (mUC) in a locally advanced/metastatic setting, and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting.
15) Phase 2 Cohort 1a (mNSCLC): Patients with NSCLC who have had treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Patients treated with a taxane within 12 months or patients refractory to prior taxane treatment are excluded. Patients who were treated for EGFR, ROS1, ALK, NTRK, or MET exon 14 genomic alterations are excluded.
16) Phase 2 Cohort 1b (mUC): Patients with UC who have had prior treatment with systemic chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible. At least 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are required and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic
setting are allowed. Patients treated with a taxane within 12 months or patients refractory to prior taxane treatment are excluded.
17) Phase 2 Cohort 1c (mSCLC): Patients with SCLC who have had prior treatment with platinum-based chemotherapy with or without immunotherapy are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Patients treated with a taxane within 12 months

E.4

Principal exclusion criteria

1) Positive serum pregnancy test
2) Breastfeeding female
3) Active central nervous system (CNS) disease. Patients with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed
4) Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed red blood cell transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria
5) History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months
6) Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
7) Prior treatment with CD47 or signal regulatory protein alpha-targeting agents
8) Current participation in another interventional clinical trial
9) Known inherited or acquired bleeding disorders
10) Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
11) Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and who are in complete remission for over 2 years
12) Known active or chronic hepatitis B or C infection or human immunodeficiency virus infection in medical history
13) Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted. NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone releasing hormone agonists for prostate or breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappaB ligand (RANKL) inhibitors are not criteria for exclusion. There is no required minimum washout period for these therapies. Patients should be recovered from the effects of radiation.

E.5 End points

E.5.1

Primary end point(s)

- Incidence of adverse events (AEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (Appendix 4; Safety Run-in Cohort 1, Phase 2 Cohorts 1a, 1b, and 1c)
- ORR, defined as the proportion of patients who achieve a complete response or partial response, as measured by response evaluation criteria in solid tumors (RECIST), Version 1.1, as determined by investigator assessment (Phase 2 Cohorts 1a, 1b, and 1c)

E.5.1.1

Timepoint(s) of evaluation of this end point

The incidence of adverse events is assessed for the duration of the study.
Efficacy assessment scans to assess response to be taken every 9 weeks.

E.5.2

Secondary end point(s)

- PFS from date of dose initiation as determined by investigator assessment per RECIST, Version 1.1 (Phase 2 Cohorts 1a, 1b, and 1c)
- DOR, defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, per RECIST, Version 1.1, or death from any cause, whichever occurs first, as determined by investigator assessment (Phase 2 Cohorts 1a, 1b, and 1c)
- OS, defined as date of dose initiation (Phase 2 Cohorts 1a, 1b, and 1c) to death from any cause.
- Magrolimab concentration versus time and antidrug antibodies to magrolimab (Safety Run-in Cohort 1; Phase 2 Cohorts 1a, 1b, and 1c)

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy assessment scans to assess response to be taken every 9 weeks.
Blood samples for PK assessment will be collected predose at multiple timepoints according to the schedules of assessments.
Peripheral blood for immunogenicity assessments for ADA against magrolimab will be collected as described in the schedules of assessments for all patients.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Netherlands

Poland

Spain

United Kingdom

United States

France

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

128

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-10-01

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