A Study to Evaluate Sotigalimab (APX005M) in Subjects With Unresectable or Metastatic Melanoma

Exclusion Criteria

• •1. Prior Therapy:
• •1. Cohorts 1 and 2 only: Previous exposure to any immunomodulatory agent (such as CTLA-4, PD-1/PD-L1, IDO inhibitors, interferon, CD40 agonist etc.).
• •2. Cohort 3 only: Prior therapy with a CD40 agonist. Any number of prior lines of therapy are eligible. A minimum washout period of 21 days from last line of therapy until investigational therapy(ies) administration should be observed.
• •2. Second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
• •3. Active, known, clinically serious infections (≥ Grade 2 according to NCI-CTCAE v4.03) within the 14 days prior to first dose of investigational therapy(ies)
• •4. Use of systemic corticosteroids or other systemic immunosuppressive drugs within 28 days prior to first dose of investigational therapy(ies) (except inhaled corticosteroids)
• •a. The use of physiologic doses of corticosteroids may be approved /w consultation Medical Monitor (or designee)
• •5. Major surgery within 4 weeks prior to first dose of sotigalimab
• •6. Concurrent treatment with any anticancer agent and palliative radiation, unless approved by MM (or designee)
• •7. History of allogeneic bone marrow transplantation
• •8. Active, known or suspected autoimmune disease
• •9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• •10. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis
• •11. History of interstitial lung disease
• •12. History of sensitivity or allergy to mAbs or IgG
• •13. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to the first dose of investigational therapy(ies)
• •14. History of any thromboembolic event within 3 months prior to first dose of investigational therapy(ies) or active coagulopathy
• •15. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with untreated brain metastases ≤3mm that are asymptomatic, do not have significant edema, cause shift, and do not require steroids or anti-seizure medications are eligible after discussion with the Medical Monitor. Lesions of any size in posterior fossa are excluded. Subjects with previously treated brain metastases may participate provided they are stable after treatment (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using corticosteroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• •16. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection
• •17. Has received a live (attenuated) vaccine within 30 days prior to the first dose of investigational therapy(ies). Seasonal flu vaccines that do not contain live virus and COVID 19 vaccines are permitted (see Section 3.2.3.4)
• •18. Has participated in another clinical trial of an investigational drug (or a medical device) within 30 days of study enrollment
• •19. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• •20. Any clinically significant psychiatric, social, or medical condition that, in the opinion of the Investigator, could increase subject's risk, interfere with protocol adherence, or affect a subject's ability to give informed consent.