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

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

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

Study Overview

• Status: Completed
• Conditions: Superficial, Palpable, Unresectable/Metastatic Solid Tumour
• Intervention / Treatment: Drug: AGI-134

Detailed Description

Study AGI-134.FIM.101 was a Phase I/IIa, first in man (FIM), multi-center, single-arm, open-label study, designed to evaluate the safety and tolerability of escalating doses of AGI-134 as a monotherapy in unresectable/metastatic solid tumors.

The study comprised of 2 parts:

Part 1 was an accelerated escalation of the AGI-134 dose, designed to assess the safety and tolerability of AGI-134, as well as to determine the MTD (maximum tolerated dose) and recommended dose for Part 2 of the study (RP2D).

Part 2 was designed to assess the safety, tolerability and biological activity of AGI-134 at the RP2D in subjects with either deep or superficial unresectable/metastatic solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 7177871
    • Emek Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel
    • Hadassah Hebrew University Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • University of Birmingham
  • Edinburgh, United Kingdom, EH4 2XR
    • Edinburgh Cancer Research Centre
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Centre
  • London, United Kingdom, W1T 7HA
    • University Collage London
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • AHS Hospital Corp.
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic

Participation Criteria

Eligibility Criteria

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

Description

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 Adverse Event (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AGI-134 25 mg; 25 mg AGI-134 (1 mL) via intratumor 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.
Experimental: AGI-134 50 mg; 50 mg AGI-134 (2 mL) via intratumor 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.
Experimental: AGI-134 100 mg; 100 mg AGI-134 (4 mL) via intratumor 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.
Experimental: AGI-134 200 mg; 200 mg AGI-134 (8 mL) via intratumor 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of AGI-134 Injected Intra-tumourally (IT)	Safety and tolerability of AGI-134 injected intra-tumourally (IT) by assessment of the percentage of participants who experienced a dose-limiting toxicity (DLT) . DLTs will be assessed during the first cycle (21 days)	Up to 3 weeks after first administration of each dose level
Discontinue Study Drug Due to an Adverse Events	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	Approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics profile of AGI-134 (Plasma Drug Concentration of AGI-134)	Plasma Drug Concentration of AGI-134, when administered as monotherapy	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
Change in Immune-Response Following AGI-134 Administration	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	On Baseline visit, at the end of cycle 3 (which is 3 weeks long) and in week 54
Change in Disease Biomarker Following AGI-134 Administration	Assessment of the disease biomarkers that may serve as surrogates or predictors of AGI-134 clinical efficacy	On Baseline visit, at the end of cycle 3 (which is 3 weeks long) and in week 54

Collaborators and Investigators

• Sponsor: Agalimmune Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2018
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AGI-134.FIM.101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No