First-in-human Study of DB-1419 for Advanced/Metastatic Solid Tumors

Exclusion Criteria14

• Prior treatment with B7-H3 targeted therapy or prior treatment with ADC containing a topoisomerase I inhibitor payload.
• Has a medical history of symptomatic congestive heart failure (New York Heart Association \[NYHA\] classes II-IV or serious cardiac arrhythmia requiring treatment.
• Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
• Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate.
• Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis which needs glucocorticoids and antibiotics) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
• Has a history of underlying pulmonary disorder including, but not limited to, pulmonary emboli within 3 months of the start of study treatment, severe asthma, severe COPD, restrictive lung disease, and other clinically significant pulmonary compromise or requirement for supplemental oxygen.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
• Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals within 2 weeks before first dose of study treatment.
• Know human immunodeficiency virus (HIV) infection.
• Has active viral hepatitis.
• Is a lactating mother, or pregnant as confirmed by pregnancy tests performed within 7 days prior to enrollment.
• Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with asymptomatic CNS metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed therapy, and are on stable or decreasing doses of corticosteroids equivalent to ≤10 mg/day prednisone are eligible for study entry.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 5.0, Grade ≤ 1 or baseline.
• Has a prior history of immune-related adverse event that required permanent immune checkpoint inhibitor discontinuation per NCCN guidelines.