Safety, Pharmacokinetics (PK), and Efficacy of ONC-783 in Advanced Solid Tumors

A Multicenter, Open-label Study to Evaluate the Safety, Pharmacokinetics (PK), and Efficacy of ONC-783 in Advanced Solid Tumors

ONC-783-001 is a Phase I open label, dose-escalation study for evaluating the safety, pharmacokinetics (PK) and efficacy of ONC-783 as a single agent in patients with advanced/metastatic solid tumors, focusing on colorectal cancer, ovarian cancer, pancreatic cancer, or breast cancer.

This is a first in human study on a novel bispecific antibody, ONC-783, targeting cancer specific neoantigen CD24 on tumor cells and CD3 on T cells. CD24 is over-expressed in about 70% of solid tumors and hematological malignancies. CD24 overexpression is associated with poor prognosis. Cancer-specific neo-CD24 epitope will distinguish malignant CD24 from physiological CD24. This study is a multi-level dose escalation study with ONC-783 to test the safety, PK, and efficacy in patients with solid tumors.

Inclusion Criteria:

• Age ≥ 18 yrs old.
• Male or Female
• Must have ECOG score ≤ 1. The body weight should be ≥40 kg. The life expectance should be estimated ≥ 12 weeks.
• A histological or cytological diagnosis of metastatic or locally advanced pancreatic cancer, ovarian cancer, colorectal cancer, or breast cancer.
• Must have measurable target lesion according to RECIST V1.1.
• Adequate organ function as determined by laboratory tests.
• Voluntary agreement to participate as evidenced by written informed consent.
• Female patient of childbearing potential: negative pregnancy test and agreement on highly effective contraceptive methods.
• Male patient: agreement on contraceptive methods.

Exclusion Criteria:

• Patients who have not recovered to NCI CTCAE Grade ≤ 1 from an adverse event (AE) due to cancer therapeutics except the Grade ≤ 2 chemotherapy-associated peripheral neuropathy (motor or sensory) or alopecia. Patients with ongoing and adequately controlled Grade ≤ 2 endocrine immune-related AEs are considered stable and eligible for enrollment.
• The washout period for cancer therapeutic drugs (such as chemotherapy, radiation or targeted therapy) is 21 days or 28 days for monoclonal antibody therapy. Palliative radiotherapy for painful metastases or metastases in potentially sensitive locations (e.g., epidural space) ≥ 7 days prior to the first dose of study drug is allowed. Best supportive care, such as thyroxine, insulin, steroid replacement treatment, growth factors and therapy for non-cancer conditions are allowed.
• Patients who are currently enrolled in any other clinical trial testing an investigational agent or device, or with concurrent anticancer treatment (except palliative bone-directed radiotherapy), immune therapy, or cytokine therapy or anticipated to require another antineoplastic therapy during the study.
• Patients who are on chronic systemic steroid therapy at doses higher than 10 mg/day prednisone or equivalent within 7 days before first treatment.
• Patients who have active brain metastases or leptomeningeal metastases. Patients are eligible if brain metastases are adequately treated or not felt to require local treatment (i.e. < 10 mm asymptomatic) and patients are asymptomatic or neurologically stable (except for residual signs or symptoms related to the central nervous system (CNS) treatment). Note: Patients with previously treated brain metastases may participate provided that they are radiologically stable, clinically stable, and not requiring steroid treatment within 14 days before the first dose of study treatment.
• Patient with a different cancer other than the one treated under this protocol, which requires systemic treatments within 24 months prior to C1D1.
• Patient has history of Grade ≥3 allergic or hypersensitivity to SC injected medications, or severe allergic reactions to food, pollen, oral medications, or atopic dermatitis or asthmatic episodes that required hospitalization.
• QTcF (QT interval corrected for heart rate using Fridericia formula) >480 msec on screening ECG
• Within past 6 months with history of significant cardiovascular events including acute myocardial infarction, acute coronary syndrome, ischemic or hemorrhagic stroke, heart failure NYHA class III or IV, or revascularization procedures.
• Patients who have acute infections which require systemic IV drug treatments within 7 days prior to C1D1. Oral drug or prophylaxis treatment is allowed.
• Patients who, in the opinion of the treating Investigator, have a history or current evidence of any medical or psychiatric conditions that would limit their ability to comply with all aspects of the trial or on a therapy, or with a significant laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or make study participation not in the best interest of the patient. Investigators should discuss the case with the Sponsor.
• Patients who are pregnant or breastfeeding, or who intend to become pregnant or father a child during the study or within 6 months after the last dosing of study drug.