Overview

This Phase I/IIa trial is designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of CyPep-1 when administered directly into malignant tumors. Additionally, the trial will monitor anti-tumor effects on both injected lesions and distant non-injected deposits.

Eligibility

Inclusion Criteria:

1. Histologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) solid tumor malignancy (including lymphomas) that is refractory to standard-of-care treatment or for which there is no standard therapy considered appropriate. Metastatic deposits (including cutaneous/subcutaneous lesions and metastatic deposits in lymph nodes) of tumors for which IT injections may be performed are eligible. Pure cutaneous infiltrations (e.g., breast cancer cutaneous carcinomatosis) are ineligible.
2. 1 to 3 non-ulcerated transcutaneously accessible lesion(s) for injection and measurable as defined by iRECIST v1.1. All other tumor lesion(s) may be selected for efficacy follow-up, but will not be subjected to treatment with CyPep-1.
3. Presence of tumor lesion(s) (that have not been previously irradiated) suitable for biopsy at screening and at Week 6, among which one target lesion for CyPep-1 treatment is mandatory and if possible, also one non-injected lesion.
4. Age 18 years.
5. Estimated life expectancy of at least 3 months.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B)
7. Resolution of toxicity due to prior therapy to Grade < 2 (except for alopecia and transaminases in case of liver metastases) as defined by CTCAE v5.0.
8. Ability to give written informed consent and to comply with the protocol.
9. All subjects of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must have a negative high sensitive pregnancy test at screening (urine/serum) and agree to use highly effective method for contraception according to the EU Clinical Trial Facilitation Group guidance from time of signing Informed Consent until at least 120 days after the last administration of CyPep-1. The partners of subjects with childbearing potential must also apply contraceptive methods and are recommended not to donate sperm.
10. Adequate bone marrow, liver, and renal function:
11. Platelet count 100 x 109/L
12. Hemoglobin 6.0 mmol/L or 9.67 g/dL
13. Absolute Neutrophil Count (ANC) 1.5 x 109/L
14. Total bilirubin 1.5 x ULN, except for subjects with familial bilirubinemia (Gilbert's disease)
15. Serum ASAT and ALAT 2.5 x ULN ( 5 x ULN in case of liver metastases)
16. Creatinine clearance 30 mL/min (by Cockcroft-Gault formula)

Exclusion Criteria:

1. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds delivered by IT injection, including investigational agents.
2. Participation in another clinical trial within 4 weeks prior to first dose of CyPep-1.
3. Anti-cancer therapy within 4 weeks prior to the first dose of CyPep-1 (within 2 weeks for palliative radiotherapy, within 1 week for endocrine therapy).
4. Major surgical procedure within 14 days prior to the first dose of CyPep-1.
5. Live vaccine within 30 days prior to first dose of CyPep-1.
6. Expected to require any other form of systemic or localized antineoplastic therapy while in this trial. Localized palliative radiotherapy for pain relieve is allowed on tumor lesions that are not selected for evaluation of treatment response.
7. Clinical evidence of an active second malignancy that is progressing or requires active treatment, except for curatively treated early stage (carcinoma in situ or stage 1) carcinomas or non-melanoma skin cancer.
8. Active autoimmune disease requiring immunosuppressive therapy.
9. Any condition requiring continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive agents within 2 weeks prior to first dose of CyPep-1. Inhaled, intranasal or topical (only on areas outside the target lesion(s)) and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active auto-immune disease.
10. Abnormal or clinically significant coagulation parameters at the discretion of the investigator, i.e.:
    • Prothrombin Time - International Normalized Ratio (PT-INR)
    • Activated Partial Thromboplastin Time (APTT) Subjects being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the SmPC for the administered treatment.
11. Subjects on anticoagulants for whom temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy at the discretion of the investigator and/or per local standard of care) during treatment period, is not an option.
12. Past history of severe allergic episodes and/or Quincke's edema.
13. Known hypersensitivity to any component of CyPep-1.
14. Prior allogeneic tissue/solid organ transplant, stem cell or bone marrow transplant.
15. Known active human immunodeficiency virus (HIV). Subject is eligible when normal levels of CD4 are present.
16. Central nervous system (CNS) metastasis that is symptomatic or progressing or that requires current therapy (e.g., evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastasis).
17. QTcF > 480 ms, history of long or short QT syndrome, Brugada syndrome, or known history of QTc prolongation, or Torsade de Pointes.
18. Women who are pregnant or breastfeeding.
19. Any serious and/or unstable pre-existing medical, psychiatric or other condition which in the investigator's opinion could interfere with subject safety, obtaining written informed consent, or compliance with the trial protocol.