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

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ClinicalTrials.gov Identifier: NCT03593226
Recruitment Status : Recruiting
First Posted : July 20, 2018
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
Agalimmune Ltd.

Brief Summary:
This study will evaluate if AGI-134 given alone and in combination with pembrolizumab is safe and effective in treating patients with unresectable metastatic solid tumours.

Condition or disease Intervention/treatment Phase
Superficial, Palpable, Unresectable/Metastatic Solid Tumour Metastatic Colorectal Cancer Squamous Cell Carcinoma of the Head and Neck Drug: AGI-134 Drug: AGI-134 + Pembrolizumab 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 and in combination with pembrolizumab 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 and in a group of subjects who will receive AGI-134 in combination with Pembrolizumab.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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 and in combination with pembrolizumab at the RP2D.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIA, Multicenter, Two Parts, Open-Label Study Designed to Evaluate the Safety and Tolerability of Escalating Doses of AGI-134 Given as Monotherapy and in Combination With Pembrolizumab, in Unresectable Metastatic Solid Tumours
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine


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.

Experimental: AGI-134 + Pembrolizumab
AGI-134 every three weeks for 4 cycles in combination with Pembrolizumab. Pembrolizumab will continue to be administered IV for a total of up to 17 cycles (one year of treatment).
Drug: AGI-134 + Pembrolizumab
AGI-134 every three weeks for 4 cycles in combination with Pembrolizumab. Pembrolizumab will continue to be administered IV for a total of up to 17 cycles (one year of treatment).




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. Percentage of Participants Who Discontinue Study Drug Due to an Adverse Events [ Time Frame: 12 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 and as combination therapy with Pembrolizumab

  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



Information from the National Library of Medicine

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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. With a histologically - or cytologically - confirmed unresectable metastatic solid tumour and who have received, or been intolerant to, all treatment options known to confer clinical benefit.
  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 ≥1 injectable lesion which is amenable to injection and biopsy and is measurable according to RECIST v1.1.
  7. Has ≥1 metastatic lesion which is amenable for biopsy.
  8. Evaluable Disease according to RECIST v1.1
  9. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  10. Has a life expectancy >3 months
  11. Adequate organ function
  12. Women of childbearing potential and all men must agree to use an adequate contraception
  13. Subject is able and willing to comply with the requirements of the protocol.
  14. 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

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 trial 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.

26. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis 27. Has a history of interstitial lung disease.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03593226


Contacts
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Contact: Shimrit Yefet, B.A +972-8-642-9100 ext 159 shimrity@biolinerx.com

Locations
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Israel
Rambam Health Care Campus Recruiting
Haifa, Israel, 3109601
Principal Investigator: Ruth Perets, MD         
Sheba Medical Center Not yet recruiting
Ramat Gan, Israel, 52621
Principal Investigator: Talia Golan, MD         
Tel Aviv Sourasky Medical Center Not yet recruiting
Tel Aviv, Israel, 6423906
Principal Investigator: Ravit Geva, MD         
United Kingdom
University of Birmingham Not yet recruiting
Birmingham, United Kingdom, B15 2TT
Principal Investigator: Gary Middleton, MD         
Edinburgh Cancer Research Centre Not yet recruiting
Edinburgh, United Kingdom, EH4 2XR
Principal Investigator: Stefan Symeonides, MD         
The Beatson West of Scotland Cancer Centre Not yet recruiting
Glasgow, United Kingdom, G12 0YN
Principal Investigator: Jeff Evans, MD         
University Collage London Not yet recruiting
London, United Kingdom, W1T 7HA
Principal Investigator: Martin Forster, MD         
The Christie NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Fiona Thistlethwaite, MD         
Churchill Hospital Not yet recruiting
Oxford, United Kingdom, OX3 7LE
Principal Investigator: Mark R Middleton, MD         
University Hospital Southampton Withdrawn
Southampton, United Kingdom, S016 6YD
Sponsors and Collaborators
Agalimmune Ltd.

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Responsible Party: Agalimmune Ltd.
ClinicalTrials.gov Identifier: NCT03593226     History of Changes
Other Study ID Numbers: AGI-134.FIM.101
First Posted: July 20, 2018    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
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Colorectal Neoplasms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents