A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies

Exclusion Criteria

• •1. Subject has received prior treatment with systemic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies (e.g., checkpoint inhibitors) within 28 days or five half-lives of the drug, whichever is shorter.
• •2. Subject has ongoing toxicity from prior therapy \>Grade 1 according to the CTCAE, with the following exceptions. Such exceptions must be assessed by the Investigator (and approved by the Sponsor) as not placing the subject at undue safety risk from participating in this study.
• •1. Alopecia, and vitiligo
• •2. Grade ≤2 neuropathy
• •3. Well-controlled hypo/hyperthyroidism or other endocrinopathies that are well controlled with hormone replacement
• •3. Subject has undergone a major surgery (excluding minor procedures e.g., placement of vascular access) \<2 months prior to administration of PRTH-101.
• •4. Subject has received radiation therapy \<28 days prior to administration of PRTH-101.
• •a. Exception: limited (e.g., pain palliation) radiation therapy is allowed prior to and during study treatment as long as there are no acute toxicities, and the subject has measurable disease outside the radiation field.
• •5. Subject has undergone or is anticipated to undergo organ transplantation including allogeneic or autologous stem-cell transplantation, at any time.
• •6. Subject has a diagnosis of immunodeficiency, either primary or acquired.
• •7. Subject has received treatment with systemic steroids or any other form of immunosuppressive therapy within 14 days prior to administration of PRTH-101.
• •a. Exception: inhaled or topical (to include mouthwash) steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease.
• •8. Subject has an active or prior history of autoimmune disease requiring immunosuppressive therapy. Exceptions can be made in discussion with the medical monitor.
• •9. Subject has a known severe intolerance to or hypersensitivity reactions to monoclonal antibodies, Fc-bearing proteins (e.g., soluble receptors or other Fc fusion proteins), or IV immunoglobulin preparations; prior history of human antihuman antibody response; known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• •10. Subject has Central Nervous System (CNS) tumor involvement not definitively treated with surgery or radiation that is active (including evidence of cerebral edema by MRI, or progression from prior imaging study, or has had any requirement for steroids, or clinical symptoms of/from CNS metastases within 28 days prior to study treatment.
• •11. Subject has leptomeningeal carcinomatosis, regardless of treatment history.
• •12. Subject has current second malignancy at other sites (exceptions: nonmelanomatous skin cancer, adequately treated in situ carcinoma \[e.g., cervical\], or indolent prostate cancer under observation). A history of other malignancies is allowed as long as subject has been free of recurrence for ≥2 years, or if the subject has been treated with curative intent within the past 2 years and, in the opinion of the Investigator, is unlikely to have a recurrence.
• •13. Subject has active and clinically significant bacterial, fungal, or viral infection, including known Hepatitis A, B, or C or HIV (testing not required).
• •14. Subject has received live vaccines within the past 30 days (inactivated vaccines are allowed; seasonal vaccines should be up to date \>30 days prior to administration of PRTH-101).
• •15. Women who are pregnant or breastfeeding.
• •16. History of any of the following ≤6 months before first dose:
• •a. Congestive heart failure New York Heart Association Grade III or IV b. Unstable angina c. Myocardial infarction d. Unstable symptomatic ischemic heart disease e. Uncontrolled hypertension despite appropriate medical therapy f. Ongoing symptomatic cardiac arrhythmias of \> Grade 2 g. Symptomatic cerebrovascular events, or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy); chronic atrial fibrillation on stable anticoagulant therapy is allowed.
• •17. Subject has any contraindications to the imaging assessments or other study procedures that subjects will be undergoing.
• •18. Subject has any medical or social condition that, in the opinion of the Investigator, might place a subject at increased risk, affect compliance, or confound safety or other clinical study data interpretation.