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

Inclusion Criteria:

* Male or female patients, ≥18 years.
* Documented (histologically or cytologically proven), locally advanced or metastatic solid tumor malignancy (must be one of the following):

  1. Squamous cell carcinoma of the head and neck
  2. Non-small-cell lung carcinoma-adenocarcinoma histology subtype
  3. Pancreatic ductal adenocarcinoma
  4. Cholangiocarcinoma
  5. Colorectal carcinoma (microsatellite stable \[MSS\] and microsatellite instability-high \[MSI-H\] phenotypes)
  6. Gastric carcinoma (includes gastroesophageal carcinoma)
  7. Esophageal carcinoma (includes squamous cell and adenocarcinoma)
  8. Mesothelioma (pleural and peritoneal)
  9. 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.

Exclusion Criteria:

* Central nervous system (CNS) malignancies.
* Clinically significant cardiovascular disease or condition.
* Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study drug(s).
* 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.
* History of significant toxicities associated with previous administration of immune checkpoint inhibitors.
* Known or suspected hypersensitivity to any of the excipients of formulated study drug.
* 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).
* Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy).

Therapeutic Exclusions

* 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 antineoplastic agent for the primary malignancy (standard or investigational) within 4 weeks or 5 elimination half-lives.
* 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).