First-in-human Study of DB-1305/BNT325 for Advanced/Metastatic Solid Tumors

This is a multicenter, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.

Inclusion criteria

• Male or female adults (defined as ≥ 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).
• Histologically or cytologically confirmed unresectable advanced/ metastatic solid tumors who have relapsed or progressed on or after standard systemic treatments or for which no standard treatment is available.
• At least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria.
• Has a life expectancy of ≥ 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Has Left Ventricular Ejection Fraction (LVEF) ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
• Has adequate organ functions within 7 days prior to Day 1 of Cycle 1.
• Has adequate treatment washout period prior to Day 1 of Cycle 1.
• Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of Trop-2 level and other biomarkers if not contraindicated.
• Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.

Exclusion criteria

• Has a medical history of symptomatic congestive heart failure (CHF) (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 non-infectious Interstitial Lung Diseases (ILD)/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has a lung-specific intercurrent clinically significant illness.
• Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
• Subjects have human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness are not eligible for enrollment; However, subjects have had HIV infection with a cluster of differentiation 4 (CD4)+ T cell count > 350 cells/µL and no history of an AIDS-defining illness are eligible for entry.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.