Study to Evaluate Safety & Tolerability of AGI-134 in Solid Tumour

• ClinicalTrials.gov Identifier: NCT03593226
• Recruitment Status: Active, not recruiting
• First Posted: July 20, 2018
• Last Update Posted: August 2, 2022
• Sponsor: Agalimmune Ltd.
• Information provided by (Responsible Party): Agalimmune Ltd.

Study Description

Brief Summary:

This study will evaluate if AGI-134 given alone is safe and tolerate in treating patients with unresectable/metastatic solid tumours.

Condition or disease	Intervention/treatment	Phase
Superficial, Palpable, Unresectable/Metastatic Solid Tumour	Drug: AGI-134	Phase 1; Phase 2

Detailed Description:

Unresectable solid tumour is a tumour that cannot be removed completely through surgery, radiation therapy, drug treatment or any combination of them.

AGI-134 (alpha-Gal) is a synthetic molecule that by intratumoural injection trigger a systemic anti-tumour response.

This study will evaluate the safety, tolerability and efficacy of AGI-134 given alone in treating patients with unresectable metastatic solid tumours.

This study is divided to 2 parts:

Part 1 will assess on a small group of subjects the safety and tolerability of increasing doses of AGI-134 injected intra-tumourally (IT) and will determine the maximum AGI-134 dose that can be tolerated.

Part 2 will assess the safety, tolerability and clinical effect of the dose selected in part 1 in a group of subjects who will receive AGI-134 alone injected intra-tumourally.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment

Intervention Model Description

Part 1- Accelerated escalation This is an accelerated escalation dose study designed to assess the safety and tolerability of escalating doses of AGI-134, as well as the Maximum Tolerated Dose (MTD) and the part 2 dose (RP2D).

Part 2 - Will comprise of two cohorts aiming to assess the safety, tolerability and anti-tumour activity of AGI-134 as a monotherapy

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/IIA, Multicentre, Two Parts, Open-Label Study Designed to Evaluate the Safety and Tolerability of Escalating Doses of AGI-134 in Unresectable/Metastatic Solid Tumours
• Actual Study Start Date: November 15, 2018
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: AGI-134; AGI-134 via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles.	Drug: AGI-134; AGI-134 via IT injection. The proposed treatment is one dose of AGI-134 monotherapy per cycle; each cycle consists in three weeks, dosing will be given for 4 cycles.

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of AGI-134 injected intra-tumourally (IT) by assessing the percentage of participants who experience a dose-limiting toxicity (DLT) [ Time Frame: Up to 3 weeks at each dose level ]
   Percentage of participants who experience a dose-limiting toxicity (DLT) . DLTs will be assessed during the first cycle (21 days)
2. Discontinue Study Drug Due to an Adverse Events [ Time Frame: 54 weeks ]
   Percentage of Participants Who Discontinue Study Drug Due to an Adverse Event (AE) AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE. The percentage of participants who discontinue study treatment due to an AE will be presented

Secondary Outcome Measures :

1. Pharmacokinetics profile of AGI-134 (Plasma Drug Concentration of AGI-134) [ Time Frame: At the beginning of cycles 1, 2, 3 and 4 (each cycle is 3 weeks long) prior to the drug administration and up to 72 hours post drug administration ]
   Plasma Drug Concentration of AGI-134, when administered as monotherapy
2. Change in Immune-Response Following AGI-134 Administration [ Time Frame: On Baseline visit, at the end of cycle 3 (which is 3 weeks long) and in week 54 ]
   Assessment of the immune-response to AGI-134 to support the Mechanism of Action (MoA) that may serve as surrogates or predictors of clinical efficacy
3. Change in Disease Biomarker Following AGI-134 Administration [ Time Frame: On Baseline visit, at the end of cycle 3 (which is 3 weeks long) and in week 54 ]
   Assessment of the disease biomarkers that may serve as surrogates or predictors of AGI-134 clinical efficacy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 demonstrated to prolong survival.
3. Subjects should have at least two measurable lesions based on RECIST v1.1 as determined by the site study team.
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. With sufficient tumour size for IT injection

6. Has ≥ 2 lesions:

   Has ≥1 injectable lesion which is amenable to injection and biopsy and is measurable according to RECIST v1.1.

   Has ≥1 metastatic lesion 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
11. Women of childbearing potential and all men must agree to use 2 methods of an adequate contraception
12. Subject is able and willing to comply with the requirements of the protocol.
13. Subject is able to voluntarily provide written informed consent.

Exclusion Criteria:

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
4. History of or plan for splenectomy or splenic irradiation
5. History of organ transplant or currently taking active immunosuppressive therapy
6. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
7. Has known active or chronic Hepatitis B or Hepatitis C
8. History or evidence of cancer associated with immunodeficiency states
9. 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 trial treatment.
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 trial treatment.
13. Has positive Immunoglobulin E (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 trial, starting with the screening visit through 120 days after the last dose of trial treatment.
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
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 finding or a laboratory abnormality that the Investigator considers would make the subject a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
25. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Contacts and Locations

Locations

United States, California

UCLA

Los Angeles, California, United States, 90095

United States, New Jersey

AHS Hospital Corp.

Morristown, New Jersey, United States, 07960

United States, Oregon

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States, 97213

Israel

Emek Medical Center

Afula, Israel, 7177871

Rambam Health Care Campus

Haifa, Israel, 3109601

Hadassah Hebrew University Medical Center

Jerusalem, Israel

Sheba Medical Center

Ramat Gan, Israel, 52621

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

United Kingdom

University of Birmingham

Birmingham, United Kingdom, B15 2TT

Edinburgh Cancer Research Centre

Edinburgh, United Kingdom, EH4 2XR

The Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

University Collage London

London, United Kingdom, W1T 7HA

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Churchill Hospital

Oxford, United Kingdom, OX3 7LE

Sponsors and Collaborators

Agalimmune Ltd.

More Information

• Responsible Party: Agalimmune Ltd.
• ClinicalTrials.gov Identifier: NCT03593226
• Other Study ID Numbers: AGI-134.FIM.101
• First Posted: July 20, 2018
• Last Update Posted: August 2, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms