Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies

Prior treatment

• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study drug(s).
• History of significant toxicities associated with previous administration of immune checkpoint inhibitors.
• Unresolved \>Grade 1 toxicity associated with any prior antineoplastic therapy.
• Inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to the first dose of study drug(s).
• Prior therapy with Sym024 or other inhibitors of CD73, CD39 or adenosine receptors ADORA2A, ADORA2B.
• Part II and Part III, prior anti-PD-(L)1 therapy, except for indications where it is approved.
• Any other investigational treatments within 2 weeks prior to the first dose of study drug(s).
• Radiotherapy, with exceptions.
• Live vaccines against infectious diseases 4 weeks prior to the first dose of study drug(s).
• Immunosuppressive or systemic glucocorticoids therapy (\>10 mg daily prednisone or equivalent) within 2 weeks prior to the first dose of study drug(s), with exceptions.
• Prophylactic use of hematopoietic growth factors within 1 week prior to the first dose of study drug(s).

Other illness

• Central nervous system (CNS) malignancies.
• Clinically significant cardiovascular disease or condition.
• Active uncontrolled bleeding or a known bleeding diathesis.
• Significant ocular disease or condition.
• Significant pulmonary disease or condition.
• Current or recent (within 6 months) significant gastrointestinal disease or condition.
• Active, known or suspected autoimmune disease.
• History of organ transplantation (i.e., stem cell or solid organ transplant).
• Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Any other serious/active/uncontrolled infection.
• Known or suspected hypersensitivity to any of the excipients of formulated study drug.
• Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy).
  • Therapeutic Exclusions
• Any antineoplastic agent for the primary malignancy (standard or investigational) within 4 weeks or 5 elimination half-lives.

• Male or female patients, ≥18 years.
• Documented (histologically or cytologically proven), locally advanced or metastatic solid tumor malignancy (must be one of the following):
  • Squamous cell carcinoma of the head and neck
  • Non-small-cell lung carcinoma-adenocarcinoma histology subtype
  • Pancreatic ductal adenocarcinoma
  • Cholangiocarcinoma
  • Colorectal carcinoma (microsatellite stable \[MSS\] and microsatellite instability-high \[MSI-H\] phenotypes)
  • Gastric carcinoma (includes gastroesophageal carcinoma)
  • Esophageal carcinoma (includes squamous cell and adenocarcinoma)
  • Mesothelioma (pleural and peritoneal)
  • Cervical carcinoma (CC) (includes adeno, squamous and mixed adeno-squamous carcinoma histology subtypes)
• Malignancy that is not currently amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
• Measurable disease according to RECIST v1.1.
• Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
• Agreeing to mandatory tumor tissue biopsies (2 total).
• ECOG PS of 0 or 1.
• Adequate organ function as indicated by the following laboratory values.
• Adequate contraception required as appropriate.