Clinical Trials Register

Summary
EudraCT Number:	2018-002732-24
Sponsor's Protocol Code Number:	FP2CLI001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-11-23
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

UK - MHRA

A.2

EudraCT number

2018-002732-24

A.3

Full title of the trial

A Phase I/II Open–Label, Three-Part, Dose-Finding and Separate Cohort Expansion Trial to Assess the Safety, Tolerability and Preliminary Efficacy of Repeated Doses of CLEVER-1 Antibody FP-1305, in Subjects with Advanced Solid Tumours

A.3.1

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

A Study to evaluate safety, tolerability and preliminary efficacy of FP-1305 in cancer patients

A.3.2

Name or abbreviated title of the trial where available

MATINS

A.4.1

Sponsor's protocol code number

FP2CLI001

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	Faron Pharmaceuticals Ltd
B.1.3.4	Country	Finland
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	Faron Pharmaceuticals Ltd
B.4.2	Country	Finland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Faron Pharmaceuticals
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Joukahaisenkatu 6
B.5.3.2	Town/ city	Turku
B.5.3.3	Post code	FI-20520
B.5.3.4	Country	Finland
B.5.4	Telephone number	+358405656 909
B.5.6	E-mail	regulatory.affairs@faron.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.3.2	Product code	FP-1305
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	bexmarilimab
D.3.9.2	Current sponsor code	FP-1305
D.3.9.3	Other descriptive name	CLEVER-1 ANTIBODY
D.3.9.4	EV Substance Code	SUB193774
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	25
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Selected solid tumours;
- cutaneous melanoma
- pancreatic ductal adenocarcinoma
- ovarian cancer
- colorectal adenocarcinoma
- hepatocellular carcinoma
- gallbladder cancer and cholangiocarcinoma
- uveal melanoma
- gastric adenocarcinoma (including GE junction)
- estrogen receptor positive breast cancer
- anaplastic thyroid cancer

E.1.1.1

Medical condition in easily understood language

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10049280
E.1.2	Term	Solid tumour
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 safety, tolerability and recommended dose of FP-
1305 in subjects with advanced solid tumours of the selected tumour
types without standard treatment options
• To determine the safety, tolerability and preliminary efficacy of FP-1305 monotherapy with the objective response rate (ORR) and immune-related ORR (irORR) in distinct expansion groups of subjects with advanced solid tumours of the selected tumour types
• To assess the objective response rate (ORR) in distinct expansion groups of subjects with advanced solid tumours in CLEVER-1 positive subjects from selected tumour types at a selected dose

E.2.2

Secondary objectives of the trial

• To study PK after different doses
• To assess the host immune response to FP-1305 (immunogenicity)
• To assess the preliminary efficacy of FP-1305 monotherapy with the objective response rate (ORR) and immune-related ORR (irORR)
• To understand PK & ADA in different tumour types
• To determine CLEVER-1 positivity
• To assess ORR & duration of response in different tumour types
• To study population PK & ADA in different tumour types
• To determine CLEVER-1 positivity
• To assess ORR & duration of response
• To study Progression Free Survival and Overall Survival

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Voluntary Genetic sample

E.3

Principal inclusion criteria

1) Written Informed Consent
2) Aged ≥ 18 years male or female
3) Tumour sample should be collected during screening period. If a
recent tumour biopsy obtained within six months before the date of
consent is available (or older, as agreed on a case by case basis with the
sponsor), that may be used. At the discretion of the sponsor, the tumour
sample may be optional for certain subjects in Part III
4) Life expectancy > 12 weeks
5) Histologically confirmed advanced (inoperable or metastatic) malignancies in which (according to the view of the investigator) no
curative, effective or suitable treatment options exist:
• Hepatocellular carcinoma
• Gall bladder cancer or intra- or extrahepatic cholangiocarcinoma
• Colorectal adenocarcinoma
• Serous poorly differentiated (Grade 3) ovarian adenocarcinoma or undifferentiated ovarian cancer
• Pancreatic ductal adenocarcinoma
• Immunotherapy (IO) resistant cutaneous (progression during programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody therapy)
• Uveal melanoma in Parts II and III
• Gastric adenocarcinoma (including adenocarcinoma of the distal esophagus / GE junction) in Parts II and III
• ER+ breast cancer in Part II and III
o Anaplastic thyroid cancer in Parts II and III
6) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
7) Measurable disease for parts II and III
8) Adequate bone marrow, liver and kidney function defined as
Blood WBC ≥ LLN (lower limit of normal)
Blood neutrophil count ≥ 1x109/L
Blood platelet count ≥ 100x109/L, for HCC ≥ 50x109/L
Blood haemoglobin ≥ 9.0 g/dL
Creatinine clearance >40 mL/min calculated by Cockcroft-Gault formula
AST ≤ 3 X ULN (upper limit of normal; ≤ 5 x ULN when HCC or hepatic metastases are present)
ALT ≤ 3 X ULN, (≤ 5 x ULN when HCC or hepatic metastases present)
Bilirubin ≤ 1.5 X ULN
Albumin ≥ 3.0 g/dL
The most recent measurements taken during the screening period must be within the
required limits for the patient to be considered eligible (i.e. criteria met once during the screening period are not sufficient if there are more recent measurements available that are not within the required limits. It is however acceptable to repeat measurements if the initial measurements or subsequent measurements taken during the screening period are not within the required limits; the patient is eligible providing that the newest measurements are within the required limits.) However, once a subject is out of the screening period, and has had eligibility confirmed and been enrolled, the Pre-dose laboratory assessments are not subjected to inclusion criteria limits, but only for investigators assessment of subject safety.

9) Women of child-bearing potential must have a negative pregnancy test prior to trial entry
10) Women of child-bearing potential and men who have partners of child-bearing potential must be willing to practise highly effective contraception for the duration of the trial and for three months after the completion of treatment

E.4

Principal exclusion criteria

1) Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than five half-lives from a small molecule targeted therapy or oral anticancer chemotherapy before the first IMP administration
2) Any immunotherapy within preceding 6 weeks from the first IMP administration
3) Investigational therapy or major surgery within 4 weeks from the date of consent
4) Active clinically serious infection >grade 2 NCI-CTCAE version 5.0 (Appendix 5) within preceding 2 weeks from the date of consent
5) Brain metastases
6) Subject has not recovered from the previous therapies to Grade ≤1 severity as classified by the NCI-CTCAE version 5.0 (except Grade ≤2 for alopecia, neuropathy or thyroid disorders)
7) Pregnant or lactating women
8) History of second malignancy except for non-melanotic skin cancer,
cervical carcinoma in situ or superficial bladder cancer, or any other
malignancy treated previously with curative intent and more than three
years without relapse
9) Evidence of severe or uncontrolled systemic diseases, congestive cardiac failure > New York Heart Association (NYHA) class 2 (Appendix 7), Myocardial Infarction (MI) within 6 months or laboratory finding that in the view of the investigator makes it undesirable for the subject to participate in the trial
10) Any medical condition that the Investigator considers significant to compromise the safety of the subject or that impairs the interpretation of IMP toxicity assessment
11) Confirmed human immunodeficiency virus infection
12) Symptomatic cytomegalovirus infection
13) Subjects with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia)
14) The subject requires systemic corticosteroid or other immunosuppressive treatment
15) Subjects with organ transplants
16) Subjects in dialysis
17) Use of Live (attenuated) vaccines for 30 days prior to the start of study treatment, during treatment, and until last visit
18) Subject is unwilling or unable to comply with treatment and trial instructions

Specific Additional Exclusion Criteria for Hepatobiliary Cancers
1) Any ablative therapy (Radio Frequency Ablation or Percutaneous Ethanol Injection) for HCC (this should not exclude subjects if target lesion(s) have not been treated and occurred >6 weeks prior trial entry)
2) Hepatic encephalopathy
3) Ascites refractory to diuretic therapy
4) Child-Pugh score > or = 7

E.5 End points

E.5.1

Primary end point(s)

• Dose limiting toxicities (DLT) in the trial subjects
• Adverse Events
• The response (clinical benefit rate (CBR), objective response rate
(ORR) and immune-related objective response rate (irORR) separately)
to the treatment
• CLEVER-1 positivity in each tumour type

E.5.1.1

Timepoint(s) of evaluation of this end point

• DLT is evaluated on ongoing bases as 9 weeks FU for each patient
• AEs are evaluated on ongoing bases
• CBR, ORR and irORR are determined by Cycle 7 Day 1
• CLEVER-1 positivity is determined prior to IMP administration

E.5.2

Secondary end point(s)

• The PK profile of a single dose and repeated doses (in general and for each tumour type)
• Presence of ADAs (in general and for each tumour type)
• The clinical benefit rate (CBR) of objective response rate (ORR) to the treatment
• Duration of response
• Adverse Events

E.5.2.1

Timepoint(s) of evaluation of this end point

• PK within first 5 Cycles
• ADA samples periodically during treatment
• CLEVER-1 positivity is determined prior to IMP administration
• Duration of response and AEs are evaluated on an ongoing
basis

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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

Yes

E.8.1.7.1

Other trial design description

Study has 3 parts, I: Dose escalation; II Cohort expansion; III Separate cohorts

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Finland

France

Germany

Netherlands

Spain

United Kingdom

United States

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

The end of trial will be the date the overall survival data of the last subject has been collected.

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

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:

420

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

280

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

147

F.4.2

For a multinational trial

F.4.2.1

In the EEA

450

F.4.2.2

In the whole clinical trial

700

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)

The care of the subject should follow clinical routines. However, treatment can continue beyond 1 year if beneficial for the subject, judged by the investigator (provided that the clinical development and manufacturing of FP-1305 continues and not available via other routes). In such case the data collection is limited to the collection of safety monitoring parameters, tumour imaging data,treatment related adverse events (disease progression collected through AE reporting) and overall survival.

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

2018-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-19

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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