Clinical Trials Register

Summary
EudraCT Number:	2021-003461-35
Sponsor's Protocol Code Number:	20210096
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-11-17
Trial 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2021-003461-35

A.3

Full title of the trial

A Randomized, Multi-center, Double-blind, Placebo-controlled Phase 3 Study of Bemarituzumab plus Chemotherapy versus Placebo plus Chemotherapy in Subjects with Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression (FORTITUDE-101)

A.3.1

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

Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression

A.4.1

Sponsor's protocol code number

20210096

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05052801

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	Amgen 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	Amgen 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	Amgen Kft.
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Szabadság tér 7.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1054
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+361354 4700
B.5.6	E-mail	eu-hu-medinfo@amgen.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	Bemarituzumab
D.3.2	Product code	AMG 552
D.3.4	Pharmaceutical form	Solution for injection in vial
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	BEMARITUZUMAB
D.3.9.2	Current sponsor code	AMG 552
D.3.9.4	EV Substance Code	SUB195744
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	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in vial
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression

E.1.1.1

Medical condition in easily understood language

Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression

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	23.1
E.1.2	Level	LLT
E.1.2	Classification code	10084227
E.1.2	Term	Gastroesophageal junction cancer
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	10017758
E.1.2	Term	Gastric cancer
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 compare efficacy of bemarituzumab plus mFOLFOX6 to placebo plus mFOLFOX6 as assessed by overall survival (OS)

E.2.2

Secondary objectives of the trial

• To compare efficacy between the treatment arms as assessed by:
− progression-free survival (PFS)
− objective response (OR)
• To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 compared to mFOLFOX6 plus placebo
• To compare efficacy between treatment arms as assessed by:
− duration of response (DOR)
− disease control
• To assess patient reported outcomes and Quality of Life (QoL) outcomes
• To characterize the pharmacokinetics (PK) of bemarituzumab in combination with mFOLFOX6
• To characterize the immunogenicity of bemarituzumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Adults with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy
2.Confirmed fibroblast growth factor receptor 2b (FGFR2b) overexpression by immunohistochemistry (IHC) (central testing result)
3.Eastern Cooperative Oncology Group (ECOG) less than or equal to 1
4.Measurable, evaluable, or non-evaluable disease as long as evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
5.Participant has no contraindications to mFOLFOX6 chemotherapy
6.Adequate organ and bone marrow function:
- absolute neutrophil count greater than or equal to 1.5 times 10^9/L
- platelet count greater than or equal to 100 times 10^9/L
- hemoglobin greater than or equal to 9 g/dl
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times the upper limit of normal (ULN) (or less than 5 times ULN if liver involvement). Total bilirubin less than 1.5 times ULN (or less than 2 times ULN if liver involvement); with the exception of participants with Gilbert's disease)
- calculated or measured creatinine clearance (CrCl) of greater than or equal to 30 mL/minute calculated using the formula of Cockcroft and Gault
- international normalized ratio (INR) or prothrombin time (PT) less than 1.5 times ULN except for participants receiving anticoagulation, who must be on a stable dose of warfarin for 6 weeks prior to enrollment

E.4

Principal exclusion criteria

1.Prior treatment for metastatic or unresectable disease (Note: prior adjuvant or neo-adjuvant therapy for local disease is allowed if ended more than 6 months of 1st dose)
2.Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway
3.Known human epidermal growth factor receptor 2 (HER2) positive
4.Untreated or symptomatic central nervous system (CNS) disease or brain metastases
5.Peripheral sensory neuropathy greater than or equal to Grade 2
6.Clinically significant cardiac disease
7.Other malignancy within the last 2 years (exceptions for definitively treated disease)
8.Chronic or systemic ophthalmological disorders
9.Major surgery or other investigational study within 28 days of randomization
10.Palliative radiotherapy within 14 days of randomization
11.Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer

E.5 End points

E.5.1

Primary end point(s)

• Overall survival, defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive.

E.5.1.1

Timepoint(s) of evaluation of this end point

After safety follow-up visit every 3 months (± 1 month) until 336 total deaths have been observed in the study or 13 months after the last subject is enrolled (whichever occurs later).

E.5.2

Secondary end point(s)

1.Progression-free Survival (PFS)
2.Objective Response Rate (ORR)
3.Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)
4.Duration of Response (DOR)
5.Disease Control Rate
6.Mean Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)
7.Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)
8.Stomach Cancer Related Symptom Mean Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22)
9.Change from Baseline in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22)
10.Mean Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)
11.Change from Baseline Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)
12.Time to Deterioration in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22)
13.Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score
14.Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score
15.Time to Deterioration in Physical Function Score as Measured by a Subscale of European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)
16.Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma
17.Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab in Combination with mFOLFOX6 in Plasma
18.Number of Participants with an Anti-bemarituzumab Antibody Formation

E.5.2.1

Timepoint(s) of evaluation of this end point

PFS, ORR, DOR: Radiological/tumor assessment: Every 8 weeks until week 56 after cycle 1 day 1, then every 12 weeks;
until start of new anticancer therapy, disease progression, death, withdrawal of consent, or end of study, whichever occurs first.
TAEs: throughout study
For other endpoints see Schedule of Activities (SoA)

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

Yes

E.6.13.1

Other scope of the trial description

Antibody Testing Procedures, Biomarkers, Clinical Outcome Assessments

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

120

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

Australia

Brazil

Canada

Chile

Colombia

Hong Kong

Israel

Japan

Mexico

Peru

Singapore

South Africa

Taiwan

Thailand

Turkey

United States

Belgium

Bulgaria

Denmark

Estonia

France

Germany

Hungary

Italy

Latvia

Lithuania

Poland

Portugal

Romania

Spain

Sweden

Switzerland

United Kingdom

Czechia

Argentina

Greece

E.8.7

Trial has a data monitoring committee

Yes

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

The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), including any additional parts in the study (eg, long-term follow-up, additional antibody testing), as applicable.

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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

116

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

344

F.4.2.2

In the whole clinical trial

516

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

2022-01-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-12-13

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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