Clinical Trials Register

Summary
EudraCT Number:	2019-004624-38
Sponsor's Protocol Code Number:	BOT112-02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-03-13
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-004624-38

A.3

Full title of the trial

Phase IIa open-label clinical study of intratumoural administration of BO-112 in combination with pembrolizumab in subjects with liver metastasis from colorectal cancer or gastric/gastro-oesophageal junction cancer

A.3.1

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

Study of BO-112 with pembrolizumab for colorectal or gastric /gastro-oesophageal junction cancer with liver metastasis

A.4.1

Sponsor's protocol code number

BOT112-02

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	Bioncotech Therapeutics, S.L
B.1.3.4	Country	Spain
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	Bioncotech Therapeutics, S.L.
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Merck Sharp & Dohme International GmbH
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pivotal S.L.
B.5.2	Functional name of contact point	Clinical operations
B.5.3	Address:
B.5.3.1	Street Address	Calle Gobelas, 19
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28023
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34917081250
B.5.6	E-mail	maria.moreno@pivotalcr.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	BO-112
D.3.2	Product code	BO-112
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Polyinosinic:Polycytidylic acid
D.3.9.2	Current sponsor code	BO-112
D.3.9.3	Other descriptive name	Poly I:C
D.3.9.4	EV Substance Code	SUB177592
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	0.6
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.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	KEYTRUDA
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Pembrolizumab
D.3.2	Product code	MK-3475
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	Pembrolizumab
D.3.9.2	Current sponsor code	MK-3475
D.3.9.4	EV Substance Code	SUB167136
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

Colorectal cancer or gastric/gastro-oesophageal junction cancer with liver metastasis

E.1.1.1

Medical condition in easily understood language

Colorectal cancer or gastric/gastro-oesophageal junction cancer with liver metastasis

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	10063916
E.1.2	Term	Metastatic gastric 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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10052362
E.1.2	Term	Metastatic colorectal 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

• Investigation of the anti-tumour efficacy and safety of repeated IT administrations of BO-112 in metastatic liver lesions in combination with IV pembrolizumab

E.2.2

Secondary objectives of the trial

• Further characterisation of safety and of clinical activity of the combination as well as determination of systemic exposure of BO-112
• Eploratory: Evaluation of antitumoural and immunological effects in the TME of the injected lesion

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Be willing and able to give written informed consent for the study.
2.Be equal or greater than 18 years of age.
3.Have nonresectable liver metastasis(es) of colorectal or gastric/gastro-oesophageal junction cancer (GC/GEJ).
4.Have progressed during or after, or have not tolerated therapy for advanced/metastatic disease as follows. Colorectal cancer: at least 2 lines of prior therapy (1 line if hepatic recurrence after resection). Gastric or gastro-oesophageal cancer: at least 1 line of prior therapy .
5.Have at least 1 liver metastasis of minimum 20 mm in diameter that is suitable for intratumoural injection.
6.Presence of at least 1 measurable lesion according to RECIST v1.1.
7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8.Adequate haematologic and end-organ function within 2 weeks prior to the first dose of study treatment
9.Female subjects who are not pregnant or breastfeeding and at least 1 of the following conditions applies:
a)Not a woman of childbearing potential (WOCBP)
b)WOCBP who agrees to follow contraception guidance during the treatment period and for at least 120 days after the last dose of study treatment.
10.Able and willing to comply with study and follow-up procedures.

E.4

Principal exclusion criteria

1.Prior treatment with an immune checkpoint inhibitor, an agent directed to another stimulatory or co-inhibitory T-cell receptor or any Toll-like receptor (TLR) agonist.
2.Liver metastasis(es) with macroscopic tumour infiltration into the main portal vein, hepatic vein or vena cava.
3.Contraindications to tumour biopsy and injections of the hepatic metastasis(es).
4.Chemotherapy, definitive (curative) radiation, or biological cancer therapy within 4 weeks prior to the first dose of study treatment.
5.Clinically active central nervous system metastases and/or carcinomatosis meningitis.
6.Life expectancy of < 12 weeks.
7.Active infection requiring systemic therapy.
8.History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
9.Active autoimmune disease that required systemic treatment in past 2 years.
10.Known human immunodeficiency virus (HIV) infection.
11.Known history of hepatitis B or known active hepatitis C virus infection.
12.For WOCBP: pregnancy or a positive urine pregnancy test (eg within 72 hours) prior to treatment; or breastfeeding.
13.Any other medical condition which would impact the safety of the subject or interfere with the subject’s ability to comply with the study and follow-up procedures.
14.Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

E.5 End points

E.5.1

Primary end point(s)

• Efficacy: ORR based on the BOR using RECIST 1.1
• Safety: number and proportion of subjects with study treatment-related TEAEs with severity ≥ Grade 3 (NCI-CTCAE v 5.0)

E.5.1.1

Timepoint(s) of evaluation of this end point

After stage 1 and at the end of the study

E.5.2

Secondary end point(s)

• Safety: number and proportion of subjects with TEAEs (any grade)
• Safety: number and proportion of subjects with related TEAEs (any grade)
• Tolerability: number of study discontinuations due to related TEAE
• Efficacy: disease control rate (DCR = CR, PR and SD of at least 12 weeks duration) using RECIST 1.1
• Efficacy: ORR based on best overall response using RECIST modified for immune-based therapies (iRECIST)
• Efficacy: DCR = iCR, iPR + iSD of at least 12 weeks duration) using iRECIST
• Efficacy: duration of response
• Efficacy: progression-free survival / overall survival rate at 6 months
• Pharmacokinetics: systemic exposure after first BO-112 administration
• Immune cell profile of TME in injected and noninjected lesions
• Genetic (transcriptomic) analysis of the Tumour microenvironment

E.5.2.1

Timepoint(s) of evaluation of this end point

Several timepoints throughout the study and at the end of the study.

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

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

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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 months

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

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

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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