Kivu Bioscience, Inc., a San Mateo, California-based clinical-stage biotechnology company founded in 2024 by BioGeneration Ventures, has registered a first-in-human Phase I KIVU-305 clinical trial (NCT07545356) evaluating KIVU-305, a CEACAM5-directed antibody-drug conjugate (ADC), in adults with locally advanced or metastatic solid tumors. The entry of this investigational drug KIVU-305 into clinical testing reflects growing interest in next-generation site-specific ADC engineering applied to one of oncology's most historically validated surface targets, with registry metadata indicating colorectal cancer as a probable lead disease context, though the enrolled population is formally defined as pan-solid-tumor.
The FIH trial KIVU-305 (NCT07545356) is a two-part, open-label, non-randomized Phase I study enrolling approximately 76 adults aged 18 or older with histologically or pathologically confirmed advanced or metastatic solid tumor malignancy that is either resistant to standard therapy or lacks available standard options. Participants must have measurable disease per RECIST v1.1 and an ECOG performance status of 0 or 1. The trial is structured sequentially: a dose-finding arm testing multiple ascending cohorts is followed by a dose-expansion arm treating participants at the recommended expansion dose. The study is planned to begin enrolling in June 2026 at a site in Sydney, Australia, with primary completion anticipated in Q4 2027. The primary endpoint measures the incidence of treatment-emergent adverse events to establish the maximum tolerated dose. Patients with prior exposure to any ADC carrying a topoisomerase I inhibitor payload, or prior treatment with any CEACAM5-targeted therapy, are excluded.
CEACAM5 — carcinoembryonic antigen-related cell adhesion molecule 5, also known as CEA or CD66e — is a GPI-anchored glycoprotein overexpressed in approximately 90%–95% of colorectal cancers and at varying frequencies across gastric, pancreatic, and non-squamous non-small-cell lung tumors, while expression in healthy adult tissue remains low. This differential expression profile has made it a recurring ADC target. KIVU-305 uses a humanized, Fc-silenced anti-CEACAM5 antibody conjugated via Synaffix's GlycoConnect site-specific platform, which attaches the linker-payload at the conserved N297 asparagine in the Fc region to produce a homogeneous drug-to-antibody ratio. A hydrophilic HydraSpace spacer linker is intended to improve plasma stability and reduce aggregation, and the payload — SYNtecan E, part of Synaffix's toxSYN family — is an exatecan-class topoisomerase I inhibitor. Kivu raised a USD 92 million Series A in October 2024, led by Novo Holdings, to advance this pipeline to the clinic.
The most clinically advanced comparator in the same target class is precemtabart tocentecan (M9140), developed by Merck KGaA/EMD Serono, which is currently recruiting in Phase I/II across multiple PROCEADE studies including NCT06710132 and NCT05464030. M9140 is also an anti-CEACAM5 ADC carrying an exatecan-derived payload, though it uses a higher drug-to-antibody ratio design rather than the site-specific GlycoConnect architecture. KIVU-305's Fc-silencing and homogeneous conjugation approach represents the principal engineering distinction from M9140, with the rationale that tighter DAR control and reduced off-tumor immune effector activity may improve the therapeutic index, though this remains to be demonstrated in human subjects.
Spot something wrong? Report an issue with this article