AO-176 in Multiple Solid Tumor Malignancies

Inclusion Criteria

• Select advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist, or is no longer effective Part A:
• Epithelial ovarian carcinoma (EOC)
• Endometrial carcinoma
• Castration resistant prostate cancer
• Non-small cell lung adenocarcinoma
• Papillary thyroid carcinoma
• Malignant mesothelioma (pleural or peritoneal)
• Gastroesophageal adenocarcinoma
• Squamous cell carcinoma of the head and neck Part B and Part C:
• Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer)
• Endometrial carcinoma
• Gastric adenocarcinoma/gastroesophageal adenocarcinoma
• Measurable disease
• ECOG status 0-1
• Resolution of prior-therapy-related adverse effects
• Minimum of 4 weeks or 5 half-lives since last dose of cancer therapy Key

Exclusion Criteria

• Previous hypersensitivity reaction to treatment with another monoclonal antibody
• Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only). Patients who have been desensitized may participate.
• Part C Only
• History of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or significant immune mediated skin reactions such as toxic epidermal necrolitis or Stevens -Johnson Syndrome
• History of any autoimmune disease which required systemic therapy* in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) including but not limited to: i. Inflammatory bowel disease (including ulcerative colitis and Crohn's Disease) ii. Rheumatoid arthritis iii. Systemic progressive sclerosis (scleroderma) iv. Systemic lupus erythematosus v. Autoimmune vasculitis (e.g. Wegener's granulomatosis) *Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed)
• Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4 weeks prior to the start of study drug
• Prior treatment with a CD47-targeted therapy
• Prior organ or stem cell transplant