Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

NCT ID: NCT03689192

Last Updated: 2023-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-17
• Study Completion Date: 2022-01-19

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARG1-18,19,20 peptide vaccine

One ARG1-vaccine every third week for 45 weeks.

Group Type: EXPERIMENTAL

ARG1-18,19,20

Intervention Type: BIOLOGICAL

300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide

Interventions

ARG1-18,19,20

300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Herlev Hospital

OTHER

Sponsor Role: lead

Responsible Party

Inge Marie Svane

MD, Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Inge Marie Svane, Prof., MD

Role: STUDY_DIRECTOR

CCIT-DK

Locations

Center for Cancer Immune Therapy Dept. of Hematology/oncology

Copenhagen, Herlev, Denmark

Countries

Denmark

References

Lorentzen CL, Martinenaite E, Kjeldsen JW, Holmstroem RB, Mork SK, Pedersen AW, Ehrnrooth E, Andersen MH, Svane IM. Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors - A phase I trial. Front Immunol. 2022 Oct 17;13:1023023. doi: 10.3389/fimmu.2022.1023023. eCollection 2022.

Reference Type: DERIVED

PMID: 36330525 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AA1809

Identifier Type: -

Identifier Source: org_study_id