Clinical Trials Register

Summary
EudraCT Number:	2018-001032-22
Sponsor's Protocol Code Number:	AGI-134.FIM.101
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:	2018-11-07
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

2018-001032-22

A.3

Full title of the trial

A phase I/IIa, multicentre, open label study designed to evaluate the safety and tolerability of escalating doses of AGI-134 in unresectable/metastatic solid tumours.

A.3.1

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

Safety and tolerability of AGI-134 in patients with solid tumours.

A.3.2

Name or abbreviated title of the trial where available

Safety and Tolerability of AGI-134

A.4.1

Sponsor's protocol code number

AGI-134.FIM.101

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03593226

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	Agalimmune Ltd.
B.1.3.4	Country	United Kingdom
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	Agalimune Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BioLineRx
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	2 HaMa’ayan Street
B.5.3.2	Town/ city	Modi’in
B.5.3.3	Post code	7177871
B.5.3.4	Country	Israel
B.5.4	Telephone number	972 8 6429100
B.5.6	E-mail	shimrity@BioLinerx.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.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	AGI-134
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1821461-84-0
D.3.9.2	Current sponsor code	AGI-134
D.3.9.4	EV Substance Code	AS1
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	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)	Yes
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

metastatic unresectable solid tumours

E.1.1.1

Medical condition in easily understood language

Solid tumors

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 assess the safety and tolerability of AGI-134 injected intratumourally as a monotherapy and to determine the maximum tolerated dose and recommended dose for study expansion.

E.2.2

Secondary objectives of the trial

characterization of the pharmacokinetic profile and assessment of clinical outcome and pharmacodynamic parameters.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult male or female aged 18 years old or older.
2. Have a histologically or cytologically confirmed unresectable metastatic solid tumour and who have received, or been intolerant to, all curative treatment options and treatments demonstration to prolong survival.
3. Subjects should have at least two measurable lesions based on RECIST v1.1 as determined by the site study team. Tumour lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. At least two lesions with the following characteristics are needed to be eligible:
• Part 1: Unresectable superficial/palpable tumour feasible for intratumoural injection from any solid tumour, and a metastatic/secondary lesion that can be assessed for abscopal effect and from which a biopsy can be taken.
• Part 2: An unresectable lesion feasible for Intratumoural injection from any type of unresectable metastatic solid tumour including deep lesions, and a metastatic/secondary lesion that can be assessed for abscopal effect and from which a biopsy can be taken
4. Subjects who are willing to undergo tumour biopsies, unless tumour is considered inaccessible or biopsy is otherwise considered not in the subject's best interest.
5. Tumour size:
• Part 1: the total size of the tumour(s) should allow injection of the total volume required at each escalation cohort. The volume can be injected in one lesion or divided into more than one lesion, but the total volume should be given according to the total dose at each escalation part. When volume is divided between several tumours, at least 1 mL should be injected into each tumour.
• Part 2: tumour dimensions should allow injection of a minimum of 1 mL AGI-134, in one lesion or more, hence the total tumour dimensions (from one or more lesions) should be of at least 1.5 cm for longest dimension.
6. Has ≥ 2 lesions; ≥1 injectable lesion which is amenable to injection and biopsy and is measurable according to RECIST v1.1, and ≥1 metastatic lesion which is amenable for biopsy and measurable according to RECIST v1.1.
7. Evaluable Disease according to RECIST v1.1
8. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
9. Has a life expectancy >3 months.
10. Adequate organ function at Screening as defined below. All laboratory assessments should be performed within 10 days prior to treatment initiation
Haematology:
 White blood cell (WBC) ≥ 2,500/mm3
 Absolute neutrophil count ≥ 1500 /mm3
 Platelet count ≥ 100,000/mm3
 Haemoglobin ≥9 g/dL or ≥5.6 mmol/L
 Haematocrit ≥30%
Renal function:
 Creatinine ≤1.5x Upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR]) can also be used in place of creatinine or CrCl) > 50 mL/min for subject with creatinine levels > 1.5x institutional ULN
Hepatic function:
 Total Bilirubin: ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN
 AST (SGOT) and alanine aminotransferase (ALT) (SGPT): ≤2.5xULN OR ≤5xULN for subjects with liver metastases
Coagulation:
 International Normalised Ratio (INR) or Prothrombin Time (PT): ≤1.5xULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
 Activated Partial Thromboplastin Time (aPTT): ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
11. Women of childbearing potential and all men must agree to use 2 methods of an adequate contraception: One barrier method (e.g. diaphragm, or condom or sponge, each of which are to be combined with a spermicide) and one hormonal method (e.g., oral, transdermal patch, implanted contraceptives, or intrauterine device) prior to study entry and for the duration of study participation through 120 days after the last dose of study treatment. Subjects that are highly unlikely to conceive (e.g., surgically sterile, postmenopausal, or not heterosexually active) are exempt. Confirmation that female subjects are not pregnant must be established by a negative serum β-human chorionic gonadotropin (βhCG) pregnancy test result obtained during Screening. Pregnancy testing is not required for postmenopausal or surgically sterilised women.
12. Subject is able and willing to comply with the requirements of the protocol.
13. Subject is able to voluntarily provide written informed consent.

E.4

Principal exclusion criteria

Subject must be excluded from participating the study if he/she:
1. Has a disease that is suitable for therapy administered with curative intent.
2. Has any active, acute, or chronic infection(s) that are uncontrolled and/or requiring treatment, such as antibiotics
3. An active autoimmune disease that has required systemic treatment in the 2 years preceding the study (i.e., with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
4. History of or plan for splenectomy or splenic irradiation
5. History of organ transplant or currently taking active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
6. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
7. Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] reactive) or Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is detected).
8. Has known Chronic Hepatitis B or C.
9. History or evidence of cancer associated with immunodeficiency states (e.g. hereditary immune deficiency, organ transplant, or leukaemia)
10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
11. Is expected to require any other form of antineoplastic therapy while on study.
12. Had received live vaccines within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chickenpox, yellow fever, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
13. Has positive IgE anti -Gal
14. Subject has a known allergy to alpha-Gal, such as red meat allergy, exposure to lone star tick (Amblyomma americanum), Ixodes ricinus/holocyclus, or Cetuximab allergy
15. Has known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
16. History or evidence of central nervous system metastases and/or carcinomatous meningitis (unless stable without treatment for at least 6 weeks and not requiring steroids)
17. Has received other experimental therapies or used an investigational device within 28 days of the first dose of treatment
18. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study Day 1 or has not recovered from AE> Grade 1 by treatment administered more than 14 days before first dose
19. Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study Day 1 or who has not recovered from AE > Grade 1 by treatment administered more than 28 days earlier.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment. Women with a positive pregnancy test within 72 hours from Baseline.
21. Has unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, uncontrolled atrial fibrillation, or current congestive heart failure with New York Heart Association Class III or higher.
22. Has a known current additional malignancy that is progressing or requires active treatment. Exceptions are non-melanoma skin lesions, adequately treated basal cell or squamous cell carcinoma that has undergone potentially curative therapy or carcinoma in-situ of the cervix.
23. O2 saturation < 92% (on room air).
24. Has an underlying medical condition that would preclude study participation or other psychological, social or physical examination (PE) finding or a laboratory abnormality that the PI considers would make the subject a poor study candidate or could interfere with protocol compliance or the interpretation of study results.
25. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

E.5 End points

E.5.1

Primary end point(s)

To assess the safety and tolerability of AGI-134 injected intratumourally, as well as to determine the Maximum Tolerated Dose (MTD) and the recommended Part 2 dose (RP2D).

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1:
a) At each dose level after the first subject has completed the first treatment cycle
b) After 3 subjects have completed the first treatment cycle if the dose level was expanded.
c) After 6 subjects have completed the first treatment cycle if the dose level was expanded due to a dose-limiting toxicity (DLT).
d) Following the first assessment of 3 subjects (or 6 if the dose level was expanded) at each cohort, the Safety Committee will meet every 6 months on a regular basis to review ongoing safety data and until the Last Patient Last Visit (LPLV)
Part 2:
a) After 3 subjects with deep injectable lesions (or 6 subjects, if expansion is needed) have completed the first cycle of treatment with AGI-134 (i.e., Cycle 1/Day 1 through D21).
b) Every 6 months to review ongoing safet

E.5.2

Secondary end point(s)

Characterization of the AGI-134 pharmacokinetic profile;
Assessment of the immune response to AGI-134 and to support the Mechanism of Action;
Assessment of biomarkers that may serve as surrogates or predictors of clinical efficacy

E.5.2.1

Timepoint(s) of evaluation of this end point

Ongoing, and upon study completion

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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)

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

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.8.6 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

Israel

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

LVLS and follow-up for up to 5 years (the last visit of the last subject ('termination visit') takes place during week 54, or earlier if the subject discontinues the trial before week 54. After the subject's study termination visit, all subjects will be contacted by phone every 9 weeks for up to 5 years or death to follow-up on response and survival status).

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1