A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies

Fecha de inicio: 19 de noviembre de 2020

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).