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Brief Title: Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

INTRODUCTION

  • Org Study ID: AA1809
  • Secondary ID: N/A
  • NTC ID: NCT03689192
  • Sponsor: Inge Marie Svane

BRIEF SUMMARY


In this phase I first-in-humans-study a vaccine consisting of arginase-1 (ARG1) peptides and
the adjuvant Montanide ISA-51 will be tested in ten patients with metastatic solid tumors.
Patients will be treated with an ARG1 vaccine every third week for 45 weeks.

DETAILED DESCRIPTION


Arginase-1 (ARG1) is an enzyme that converts the amino acid arginine into urea and ornithine.
ARG1 is mainly expressed in hepatocytes but different myeloid cells are also capable of
ARG1-expression.

An ARG1-induced arginine depletion suppresses T cell function through the impairment of the T
cell receptor (TCR)-complex. A research group from the Center for Cancer Immune Therapy
(CCIT) have identified spontaneous T cell reactivity against ARG1 peptides in peripheral
blood mononuclear cells of cancer patients and healthy donors. The theoretic background for
an ARG1 peptide vaccine is to activate ARG1-specific T cells to infiltrate the tumor
microenvironment and eliminate ARG1-expressing immunosuppressive cells. The aim is to treat
10 patients with progressive solid tumors following treatment with standard of care agents.
Patients will receive ARG1 vaccinations administered subcutaneously every third week for 45
weeks.

The primary endpoint is to evaluate safety and toxicity. Immune responses will be assessed
using blood- and tumor tissue samples and clinical responses are evaluated using RECIST 1.1.


  • Overall Status
    Recruiting
  • Start Date
    December 2018
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Adverse events evaluated by CTCAE 4.0

Primary Outcome 1 - Timeframe: One year

CONDITION

  • Non Small Cell Lung Cancer
  • Urothelial Carcinoma
  • Malignant Melanoma
  • Ovarian Cancer
  • Colorectal Cancer
  • Breast Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Metastatic Cancer

ELIGIBILITY


Inclusion Criteria:

1. Age ≥ 18

2. The patient has metastatic solid tumors (NSCLC, colorectal cancer, urothelial cancer,
breast cancer, ovarian cancer, malignant melanoma or HNSCC); progressive or recurrent
disease on or following treatment with standard of care agents

3. At least one measurable parameter according to RECIST 1.1.

4. The patient has an ECOG performance status of 0 or 1

5. Life expectancy of at least 3 months

6. Prior PD1/PD-L1 allowed

7. The patient is a female of childbearing potential with negative pregnancy test

8. For fertile women: Agreement to use contraceptive methods with a failure rate of < 1 %
per year during the treatment period and for at least 150 days 12 weeks after the
treatment. Safe contraceptive methods for women are birth control pills, intrauterine
device, contraceptive injection, contraceptive implant, contraceptive patch or
contraceptive vaginal ring.

9. For men: Agreement to use contraceptive measures and agreement to refrain from
donating sperm

10. The patient has met the following hematological and biochemical criteria:

1. AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases

2. Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total
bilirubin level > 1,5 ULN

3. Serum creatinine ≤1,5 X ULN

4. ANC (Absolute Neutrophil Count) ≥1,000/mcL

5. Platelets ≥ 75,000 /mcL

6. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L

11. Mandatory provision of archival tissue and blood for biomarker testing at baseline

12. Mandatory provision of blood for biomarker testing during the study

13. Signed declaration of consent after oral and written information about the protocol

Exclusion Criteria:

1. The patient has not recovered from surgery or is less than 4 weeks from major surgery

2. The patient has a history of life-threatening or severe immune related adverse events
on treatment with another immunotherapy and is considered to be at risk of not
recovering

3. The patient is expected to require any other form of systemic antineoplastic therapy
or radiation therapy while receiving the treatment. However, radiation therapy
treatment of non target lesion is allowed.

4. The patient has a history of severe clinical autoimmune disease

5. The patient has a history of pneumonitis, organ transplant, human immunodeficiency
virus positive, active hepatitis B or hepatitis C

6. The patient requires systemic steroids for management of immune-related adverse events
experienced on another immunotherapy

7. The patient has any condition that will interfere with patient compliance or safety
(including but not limited to psychiatric or substance abuse disorders)

8. The patient is pregnant or breastfeeding

9. The patient is unable to voluntarily agree to participate by signed informed consent
or assent

10. The patient has an active infection requiring systemic therapy

11. The patient has received a live virus vaccine within 30 days of planned start of
therapy

12. Significant medical disorder according to investigator; e.g. severe asthma or chronic
obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus

13. Concurrent treatment with other experimental drugs

14. Concurrent treatment with Valproate or Xanthin Oxidase inhibitors

15. Known side effects to Montanide ISA-51

16. Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or
hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis,
autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis
etc.

17. Severe allergy or anaphylactic reactions earlier in life

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: +45 38683868

Email: cathrine.lund.lorentzen@regionh.dk

LOCATION

Facility Status Contact
Facility: Center for Cancer Immune Therapy Dept. of Hematology/oncology
Copenhagen, Herlev 2730
Denmark
Status: Recruiting Contact:
Inge Marie Svane, Prof., MD
+4538683868
inge.marie.svane@regionh.dk