Clinical Trials Register

Summary
EudraCT Number:	2020-000849-14
Sponsor's Protocol Code Number:	N19MIM
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-06-04
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

Netherlands - Competent Authority

A.2

EudraCT number

2020-000849-14

A.3

Full title of the trial

Monalizumab and trastuzumab In Metastatic HER2-pOStive breAst cancer: MIMOSA-trial

A.3.1

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

Monalizumab and trastuzumab In Metastatic HER2-pOStive breAst cancer: MIMOSA-trial

A.4.1

Sponsor's protocol code number

N19MIM

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	NKI-AVL
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca/Medimmune
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NKI-AVL
B.5.2	Functional name of contact point	Leonie Voorwerk
B.5.3	Address:
B.5.3.1	Street Address	Plesmanlaan 121
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1066CX
B.5.3.4	Country	Netherlands
B.5.6	E-mail	l.voorwerk@nki.nl

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	Monalizumab
D.3.2	Product code	IPH2201
D.3.4	Pharmaceutical form	Powder for 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	Monalizumab
D.3.9.1	CAS number	1228763-95-8
D.3.9.2	Current sponsor code	IPH2201
D.3.9.3	Other descriptive name	MONALIZUMAB
D.3.9.4	EV Substance Code	SUB180109
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	750
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.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	Trastuzumab
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	Trastuzumab
D.3.2	Product code	L01XC03
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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB12612MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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	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

E.1.1.1

Medical condition in easily understood language

HER2 positive breast cancer with metastatic disease

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	100000004864

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 determine the activity (as measured by objective response rate by RECIST1.1) of monalizumab and trastuzumab in patients with metastatic HER2-positive breast cancer with high or low stromal tumor-infiltrating lymphocyte levels (higher or equal to 5% versus lower than 5%).

E.2.2

Secondary objectives of the trial

Secondary Objectives:
• To evaluate activity (as measured by objective response rate by RECIST1.1) in all included patients
• To evaluate progression-free survival according to RECIST1.1
• To evaluate overall survival
• To evaluate the safety of monalizumab and trastuzumab as the percentage of patients with toxicity and immune-related adverse events

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically confirmed HER2-positive (immunohistochemistry 2+ with SISH amplification or 3+ with or without SISH amplification) breast cancer. HER2-positivity must have been assessed on a metastatic lesion.
• Histological or cytological confirmed locally incurable or metastatic disease
• Accessible lesion for study biopsies.
• Administration of at least one line of palliative treatment with documented progression and a maximum of three lines of palliative chemotherapy in combination with HER2 targeting agents (TDM-1 is considered one line of palliative treatment). Trastuzumab in combination with endocrine treatment is not defined as one line of treatment.
• Documented progression during previous trastuzumab-based therapy
• Measurable disease according to RECIST1.1 (at least one target lesion)
• Left ventricular ejection fraction of 50% or higher
• WHO performance status of 0 or 1
• No signs of a visceral crisis
• Signed written informed consent
- Subjects with brain metastases are eligible if they have been treated, asymptomatic and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks prior to study registration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

E.4

Principal exclusion criteria

• uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
• known leptomeningeal disease localization
• history of having received other anticancer therapies within 2 weeks of start of the study drug
• history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mg daily prednisone equivalents) or chronic infections. Subjects with vitiligo, diabetes mellitus type I on a stable insulin regimen, psoriasis not requiring systemic treatment or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, Sjøgren’s syndrome or conditions not expected to recur in the absence of an external trigger will not be excluded from the study. Adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• prior treatment with immune checkpoint blockade or other forms of immunotherapy, such as but not limited to: anti-PD-(L)1, anti-PD-L2, anti-CTLA-4, anti-GITR or CD137/OX40 agonists
• prior treatment with HER2-based vaccines
• live vaccine within two weeks prior to start of the study, at any time during the study or within 5 months following the last dose of monalizumab. Inactivated vaccines, such as the seasonal flu vaccination, are allowed
• history of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥3), angina, myocardial infarction within 12 months prior to study treatment or ventricular arrhythmia.
• active other cancer
• positive test for hepatitis B surface virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• allogeneic stem cell or organ transplantation, HIV or active tuberculosis
• history of uncontrolled serious medical or psychiatric illness
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• current pregnancy or breastfeeding. Women of childbearing potential (WOCBP*) must use adequate contraceptive protection. WOCBP must have a negative serum or urine pregnancy test

E.5 End points

E.5.1

Primary end point(s)

objective response rate (partial response or complete response) according to RECIST1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 8 weeks

E.5.2

Secondary end point(s)

• Clinical benefit (complete response, partial response or stable disease for more than 24 weeks) according to RECIST1.1
• Progression-free survival according to RECIST1.1
• Overall survival
• Presence of toxicity and immune-related adverse events (classified according to CTCAE v5.0)

E.5.2.1

Timepoint(s) of evaluation of this end point

Response; every 8 weeks until progression of disease
Survival; until death from any cause
Toxicity; every 2 weeks until 30 days after last treatment

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

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.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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.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

2020-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-19

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