Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors
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
MeSH terms: Carcinoma; Melanoma; Squamous Cell Carcinoma of Head and Neck
Intervention: ARG1-18,19,20
Intervention description: 300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Arginase 1

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.
    

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