Tubulis has reported encouraging interim results from its Phase I/IIa NAPISTAR 1-01 trial evaluating TUB-040, a next-generation antibody-drug conjugate targeting NaPi2b in patients with platinum-resistant high-grade serous ovarian carcinoma. The data, presented at the European Society of Medical Oncology Congress 2025, demonstrated anti-tumor activity beginning at low doses with a broad therapeutic window.
Safety Profile Shows Clear Differentiation
TUB-040 was generally well tolerated across all dose levels, with the majority of treatment-emergent adverse events occurring at Grade 1 or 2. Notably, there were no fatal treatment-emergent adverse events across all cohorts and no discontinuations due to adverse events across the 1.67-3.3 mg/kg dose range.
The ADC demonstrated a distinctive safety profile compared to other topoisomerase-I ADCs, with no clinically relevant bleeding, pneumonitis, ocular toxicity, stomatitis, or neuropathy reported. Hematologic toxicity was predominantly low-grade and manageable at doses of 1.67-3.3 mg/kg.
The most common Grade 3 or higher treatment-emergent adverse events across the 1.67-3.3 mg/kg cohorts included neutropenia (22%), anemia (9%), thrombocytopenia (4%), and nausea (4%). The maximum tolerated dose was determined at 4.4 mg/kg.
Clinical Activity Without Biomarker Selection
"The interim results demonstrated a highly differentiated clinical profile for TUB-040 in the ADC field, with anti-tumor activity beginning at low doses with a broad therapeutic window that could provide treating physicians with flexibility in dosing," said Günter Fingerle-Rowson, MD PhD, Chief Medical Officer of Tubulis. "They further validate NaPi2b as a clinically valuable ADC target and confirm that our Tubutecan technology can deliver exatecan for effective tumor targeting with reduced systemic toxicity."
Principal Investigator Antonio González-Martín, MD PhD, emphasized the clinical significance of these findings: "Current treatment options for platinum-resistant ovarian cancer are constrained by low response rates, short progression-free survival, and tolerability challenges, underscoring the need for better therapies. The TUB-040 data suggest a significant advance for ADCs, since we are seeing clinical activity without the need for biomarker selection across a range of doses that were well tolerated."
Tubutecan Technology Platform
TUB-040 consists of an IgG1 antibody targeting NaPi2b equipped with Tubulis' proprietary Tubutecan technology. The ADC connects the topoisomerase I inhibitor exatecan through a cleavable linker system based on the company's proprietary P5 conjugation technology with a homogeneous drug-to-antibody ratio of 8.
The technology is based on novel chemistry for cysteine-selective conjugation, enabling the development of stable, highly targeted ADCs optimized for on-target delivery of the topoisomerase-1 inhibitor while minimizing systemic toxicity.
Expansion Plans and Future Development
Based on these encouraging results, Tubulis plans to initiate pivotal trials with TUB-040, explore earlier lines of treatment in ovarian cancer, and expand into combination regimens and new solid tumor indications. The ongoing NAPISTAR 1-01 study is also evaluating TUB-040 in adenocarcinoma non-small cell lung cancer, with first data from the NSCLC cohort to be presented at a future medical conference.
