A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers

Exclusion Criteria

• •1. Has only non-palpable cutaneous infiltrations (eg, breast cancer cutaneous carcinomatosis);
• •2. Had anti-cancer therapy within 4 weeks prior to the first dose of CyPep-1 (2 weeks for palliative radiotherapy);
• •3. Has participated in a clinical trial and received an investigational therapy within 30 days prior to the first dose of CyPep-1;
• •4. Has received or will receive a live or live attenuated vaccine within 30 days prior to the first dose of CyPep-1; Note: Seasonal flu vaccines that do not contain live vaccine are permitted. Coronavirus Disease 2019 (COVID-19) vaccines are only permitted with documentation of the date of the vaccine if the last dose of vaccine was administered \>14 days prior to the first dose of CyPep-1. The COVID-19 booster vaccine must be administered at least 14 days prior to the first dose of CyPep-1 and is not allowed during the first 3 months of the Treatment Period.
• •5. Has tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to the Screening Visit; Note: Patients who have had a known SARS-CoV-2 infection \>14 days prior to the Screening Visit are permitted at Investigator discretion and must present with no symptoms.
• •6. Has had a major surgical procedure within 14 days prior to the first dose of CyPep-1;
• •7. Is expected to require a systemic or localized antineoplastic therapy during participation in this study, excluding localized palliative radiotherapy to tumors not selected for evaluation of treatment response; Note: Use of denosumab for patients with bone metastasis is allowed.
• •8. Is pregnant or breastfeeding;
• •9. Has clinical evidence of a secondary malignancy actively progressing or requiring active treatment other than curative therapies for early stage (carcinoma in situ or Stage 1) carcinomas or non-melanoma skin cancer;
• •10. Has had any autoimmune disease requiring immunosuppressive therapy (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs) within 2 years prior to the first dose of CyPep-1; Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• •11. Has a condition requiring continuous systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of CyPep-1. Inhaled, intranasal, or topical (only on areas outside the injected lesion\[s\]) and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease;
• •12. Has abnormal or clinically significant coagulation parameters as determined by the Investigator (eg, prothrombin time, international normalized ratio, activated partial thromboplastin time) unless patients are on anticoagulants in which case it must be within appropriate clinical levels; Note: Patients who are on anticoagulants must be able to switch to a low molecular weight heparin or equivalent prior to Cycle 1 Day 1 and continue during the Treatment Period.
• •13. Has a significant history or clinical manifestation of any allergic disorders and/or Quincke's edema (as determined by the Investigator) capable of significantly altering the absorption of drugs, of constituting a risk when taking CyPep-1 or pembrolizumab, or of interfering with the interpretation of the data;
• •14. Has a known hypersensitivity to any component of CyPep-1 or pembrolizumab;
• •15. Has a history of adverse reactions from treatment with ICIs, including pembrolizumab, which resulted in discontinuation of ICI or pembrolizumab or has ongoing pembrolizumab-related toxicity event(s) as per treatment-limiting toxicity definitions, except patients with ongoing endocrine disorders that are managed with replacement therapy (ie, hypothyroidism related to prior pembrolizumab treatment);
• •16. Has an active infection requiring systemic therapy;
• •17. Has a known history of Hepatitis B or known active Hepatitis C virus infection;
• •18. Has had radiotherapy within 2 weeks prior to the first dose of CyPep-1, is in recovery from radiation toxicity, or has had radiation pneumonitis;
• •19. Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease;
• •20. Has had a prior allogeneic tissue/solid organ transplant, stem cell, or bone marrow transplant;
• •21. Has active human immunodeficiency virus (HIV). Patient is eligible when on stable antiretroviral therapy (no change in medication or dose) for at least 4 weeks prior to screening, has confirmed virologic suppression with HIV RNA less than 50 copies/mL or the lower limit of quantification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening, and has a cluster of differentiation 4+ T cell count \>350 cells/mm3 at screening. HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease will be excluded;
• •22. Have 4 or more sites involved, including the primary cancer; Note: A site is defined as an organ (eg, lung, liver, or brain) or a system (eg, lymphatic or central nervous system \[CNS\]).
• •23. Has a central nervous system (CNS) metastasis that is symptomatic, progressing, or that requires current therapy (eg, evidence of new or enlarging CNS metastasis, carcinomatous meningitis, or new neurological symptoms attributable to CNS metastasis);
• •24. Has a QTcF \>480 ms at screening, history of long or short QT syndrome, Brugada syndrome, QTc prolongation, or Torsade de Pointes, with the exception of patients with controlled atrial fibrillation, pacemaker, or bundle branch block as the QTc will be prolonged due to the widened QRS;
• •25. Are an adult under legal protection, are vulnerable, or lack the capacity to give informed consent, such as: persons deprived of liberty by a judicial or administrative decision; adult persons subject to a legal protection measure (under supervision/under guardianship); or persons under a judicial protection measure; or
• •26. Has a history of or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or make participation in the study not in the best interest of the patient, in the opinion of the Investigator.