Tubulis has announced the dosing of the first patient in its Phase I/IIa clinical trial (5-STAR 1-01, NCT06657222) evaluating TUB-030, a novel antibody-drug conjugate (ADC), for the treatment of advanced solid tumors. This multicenter study, conducted across the US and Canada, marks a significant step in expanding Tubulis' clinical pipeline.
TUB-030 is designed to target 5T4, an oncofetal antigen frequently expressed in various solid tumors. The ADC incorporates Tubulis’ proprietary Tubutecan technology, which combines P5 conjugation chemistry with the topoisomerase-1 inhibitor exatecan. This platform aims to enhance the biophysical properties of the ADC, facilitating precise and sustained delivery of the payload to the tumor site.
The 5-STAR 1-01 trial is a first-in-human, dose-escalation and optimization study. It plans to enroll up to 130 patients with advanced solid tumors. Phase I will focus on determining the safety profile and identifying the maximum tolerated dose or the optimal dose for further study. Phase IIa will concentrate on dose optimization, safety, and preliminary efficacy in selected tumor indications.
Preclinical Promise
Preclinical data presented at AACR demonstrated TUB-030's stability and minimal loss of linker-payload conjugation. In preclinical models, TUB-030 induced high and long-lasting anti-tumor responses, even at relatively low 5T4 expression levels, while maintaining a favorable safety and tolerability profile. Notably, a single treatment with TUB-030 led to tumor elimination in a triple-negative breast cancer mouse model, highlighting its potential efficacy. Preclinical analyses, including safety, efficacy, and pharmacokinetics, indicated that TUB-030 has a therapeutic window in a variety of solid tumors.
Executive Perspective
Dominik Schumacher, PhD, CEO and Co-founder of Tubulis, stated, "This milestone for TUB-030 demonstrates our ability to execute on our strategy to advance innovative programs into our proprietary pipeline and rapidly bring them into the clinic. As an organization, Tubulis has made a large step forward with two differentiated ADC molecules in clinical evaluation in less than a year. Our goal is to continue being an innovation driver in the field by delivering on the transformative potential of our platforms for patients."
Mechanism of Action
TUB-030 consists of a humanized, Fc-silenced IgG1 antibody targeting 5T4, conjugated to the topoisomerase-1 inhibitor exatecan via Tubulis’ Tubutecan technology. This technology is based on P5 conjugation chemistry, which allows for ADCs with improved linker stability and biophysical properties. The homogeneous drug-to-antibody ratio (DAR) is 8.
Clinical Strategy
"Building on our strong preclinical efficacy and safety data, we are expecting that targeting 5T4 with our high-performance ADC technology may offer a new precision therapy option for a variety of solid tumor indications," said Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis. "With our differentiated target, a strong bystander effect and efficient and durable target engagement via the Tubutecan platform, TUB-030 provides the potential to induce robust anti-tumor activity in 5T4-expressing tumors."
