- TUB-040 demonstrated robust clinical activity with a favorable safety profile and excellent tolerability in biomarker-unselected, heavily pre-treated PROC patients
- At data-cut-off on September 1, 2025, TUB-040 achieved an Overall Response Rate (ORR) of 59% (cORR 50%), with ORR ranging from 50% to 67%
- First interim results show clinical proof-of-concept (PoC) for Tubulis' Tubutecan platform candidate and validate NaPi2b as an attractive new ADC target
Tubulis today announced positive early clinical data from its NAPISTAR1-01 Phase I/IIa study (NCT06303505) in a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. Principal Investigator, Dr. Antonio González-Martín, Director Medical Oncology Department and Cancer Center Director at Clínica Universidad de Navarra, presented the results of Tubulis' lead antibody-drug conjugate (ADC), TUB-040, in platinum-resistant high-grade serous ovarian cancer (PROC-HGSOC), with a focus on dose levels 1.67 3.3 mg/kg. This is the first clinical data to validate Tubulis' proprietary Tubutecan technology, establishing clear proof of concept for the company's most advanced ADC targeting NaPi2b.
"These positive first-in-human data for TUB-040 represent a momentous milestone for Tubulis, validating our unique ADC design strategy, and offering a potential new treatment option for patients with platinum-resistant ovarian cancer," said Dr. Dominik Schumacher, Chief Executive Officer and Co-founder of Tubulis. "Supported by our recent financing, we are poised to rapidly advance TUB-040 towards pivotal trials and expand its clinical development into earlier stages of disease and additional tumor types. The data also provides a foundation to unlock the full potential of ADCs using our Tubutecan platform, expanding its impact to benefit a significant patient population."
Highlights of Tubulis' clinical data presented at ESMO 2025:
- Patient population and baseline characteristics
- As of the data cut-off on September 1, 2025, 67 patients (46 patients treated at dose levels of 1.67 3.3 mg/kg) with PROC were treated with TUB-040 for a median of 161 days (range 21-462) with 21-day treatment cycles
- Median age: 62 years (range 34-81); no patient selection for biomarkers
- All patients received a median of 4 prior lines of therapy (range 1-7) including bevacizumab (83.6%), PARP inhibitors (76.1%) and mirvetuximab soravtansine (13.4%)
- Efficacy
- In the 66 efficacy-evaluable patients who had at least one RECIST response assessment, onset of activity was observed at low doses with efficacy across a wide therapeutic range
- Responses occurred early (starting at treatment cycle 2) and deepened over time and were also seen in patients who received prior mirvetuximab soravtansine treatment including when mirvetuximab soravtansine was the most recent line of therapy
- Within the 1.67-3.3 mg/kg dose cohorts, an ORR of 59% (range of 50-67%), was achieved with a confirmed ORR of 50%; one complete response (CR) was observed at 2.5 mg/kg.
- Treatment is ongoing in 80% of patients within the 1.67 3.3 mg/kg cohorts and in 93% of all responding patients from this focus group
- The confirmed disease control rate (DCR) at 1.67 3.3 mg/kg was 96% and a confirmed DCR of 91% was reached across all cohorts at the data-cut-off with efficacy data in the 3.3 mg/kg group still continuing to mature
- 81% of patients within the 1.67 3.3 mg/kg cohorts exhibited a CA-125 response under treatment determined per GCIG standards. CA-125 is an established, prognostic and predictive tumor marker in ovarian carcinoma
- Safety and tolerability
- TUB-040 was generally well tolerated across all dose levels with the majority of treatment-emergent adverse events (TEAEs) at Grade 1 or 2
- There were no fatal TEAE's across all cohorts and no discontinuations due to adverse events across the 1.67 3.3 mg/kg cohorts
- No clinically relevant bleeding, pneumonitis, ocular toxicity, stomatitis, or neuropathy were reported, distinguishing TUB-040 from other topoisomerase-I ADCs
- Hematologic toxicity was predominately low-grade and manageable at doses of 1.67 3.3 mg/kg
- Most common =Grade 3 TEAEs across 1.67 3.3 mg/kg cohorts included: neutropenia (22% =G3), anemia (9% =G3), thrombocytopenia (4% =G3), and nausea (4% =G3)
- The maximum tolerated dose (MTD) was determined at 4.4 mg/kg
"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. 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," said Günter Fingerle-Rowson, MD PhD, Chief Medical Officer of Tubulis. "Our goal now is to accelerate TUB-040's clinical development to bring this valuable drug to patients as soon as possible."
"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," added Principal Investigator, Antonio González-Martín, MD PhD.
The ongoing NAPISTAR 1-01 study (NCT06303505) is evaluating TUB-040 in PROC-HGSOC and in adenocarcinoma non-small cell lung cancer (NSCLC). Based on these encouraging results, the company 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 first data from the NSCLC cohort will be presented at a future medical conference.
The full abstract will be published in the ESMO Congress 2025 Abstract Book, a supplement to the official ESMO journal, Annals of Oncology.
About TUB-040 and the Tubutecan Technology
Tubulis' lead antibody-drug conjugate (ADC) TUB-040 is directed against NaPi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting NaPi2b equipped with Tubulis' proprietary Tubutecan technology, connecting the Topoisomerase I inhibitor, exatecan, through a cleavable linker system based on the company's proprietary P5 conjugation technology with a homogeneous DAR of 8. Based on novel chemistry for cysteine-selective conjugation, the technology enables the development of stable, highly targeted ADCs optimized for the on-target delivery of the topoisomerase-1 inhibitor while minimizing systemic toxicity. The candidate is currently being investigated in a multicenter Phase I/IIa study (NAPISTAR1-01, NCT06303505) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC).
About Tubulis
Tubulis generates uniquely matched antibody-drug conjugates with superior biophysical properties that have demonstrated durable on-tumor delivery and long-lasting anti-tumor activity in preclinical models and first clinical proof-of-concept in platinum-resistant ovarian cancer. The two lead programs from our growing pipeline, TUB-040, targeting NaPi2b, and TUB-030, directed against 5T4, are being evaluated in the clinic in high-need solid tumor indications. We will solidify our leadership position by continuing to innovate on all aspects of ADC design leveraging our proprietary platform technologies. Our goal is to expand the therapeutic potential of this drug class for our pipeline, our partners and for patients. Visit www.tubulis.com or follow us on LinkedIn.
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Contacts:
For Tubulis
Dominik Schumacher, CEO Co-founder
Phone: +49 (0) 175 800 5594
Email: contact@tubulis.com
Media Requests for Tubulis
Trophic Communications
Stephanie May, PhD
Phone: +49 (0) 171 185 56 82
Email: tubulis@trophic.eu
