First-in-human, Open-label, Multi-site, Phase I/IIa, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT329 in Participants With Advanced Solid Tumors Known to Express CA19-9

Condition studied

Advanced Solid Cancers

Investigational medicinal product(s)

Eligibility

Primary endpoint

Parts A and B: Occurrence of dose-limiting toxicities (DLTs) within a participant per dose level., Part A, B and D: Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs per dose level., Part A, B and D: Occurrence of dose interruptions, reductions, and discontinuation of BNT329 due to TEAEs per dose level., Part D: Objective response rate (ORR) per dose level/arm. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (based on the investigator’s assessment) is observed as best overall response.

Endpoint detail

Part A, B and D: Assessment of PK parameters derived from serum / plasma concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload per dose level. Assessment of area under the curve, maximum concentration, time to reach maximum concentration, and terminal half-life, Parts A and B: ORR per dose level/arm. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (based on the investigator’s assessment) is observed as best overall response., Part A, B and D: Disease control rate (DCR) Per dose level/arm. Defined as as the proportion of participants in whom a CR or PR or SD (assessed at least 6 weeks is observed as best ORR per investigator’s assessment., Part A, B and D: Duration of response (DOR) Per dose level/arm. Defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (PD) or death from any cause, whichever occurs first., Part A, B and D: Anti-drug antibody (ADA) prevalence per dose level/cohort. Defined as the proportion of participants who are ADA positive at any timepoint (either baseline or post-baseline) (if data permit)., Part A, B and D - ADA incidence per dose level/cohort. Defined as the proportion of participants having treatment-emergent ADA (if data permit)., Part A, B and D: Progression Free Survival (PFS) defined as the time from first dose of BNT329 to first objective tumor progression (PD per RECIST 1.1 based on the investigator’s assessment) or death from any cause, whichever occurs first. Overall Survival (OS), defined as the time from first dose of BNT329 to death from any cause.