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TUB-040 demonstrated promising response rates of more than 50% across doses of the NaPi2b-targeted antibody-drug conjugate (ADC) administered to patients with platinum-resistant high-grade serous ovarian cancer, according to findings from the phase 1/2a NAPISTAR1-01 study (NCT06303505) presented at the European Society for Medical Oncology (ESMO) Congress 2025.¹

In the proof-of-concept dose escalation study, responses were seen at all doses higher than 1.67 mg/kg, including a complete response at the 2.5 mg/kg dose. At dose levels ranging from 1.67 mg/kg to 3.3 mg/kg, the objective response rate (ORR) was 59% and the disease control rate (DCR; ORR plus stable disease) was 96%. The confirmed ORR was 50%, with responses still ongoing for 93% of patients.

“We had a high rate of good responses, and 80% of patients remain on treatment, indicating durable benefit. TUB-040 demonstrated significant efficacy in [patients with] biomarker unselected, heavily pretreated platinum-resistant ovarian cancer,” principal investigator Antonio Gonzalez-Martin, MD, PhD, Director of the Cancer Center Clínica Universidad de Navarra, said during a presentation of the results. “Responses occurred early and were deepening over time, as we will show in a future presentation.”

TUB-040 is comprised of an Fc-silenced IgG1 antibody targeted to NaPi2b, an antigen that is highly overexpressed in ovarian cancer. The antibody is connected to the cytotoxic agent exatecan using a P5 linkage and a peptide-cleavable linker developed by the maker of the drug, Tubulis. The ADC has a drug-antibody ratio of 8 to 1. NaPi2b is also expressed in lung adenocarcinoma, with another arm of the NAPISTAR1-01 study also exploring the agent for patients with non–small cell lung cancer (NSCLC).

In the study, 67 patients with ovarian cancer were enrolled to received TUB-040 across doses ranging from 0.5 mg/kg to a planned dose as high as 5.3 mg/kg. Data presented at ESMO focused on the 46 patients enrolled at dose level 1.67 mg/kg (n = 10), 2.1 mg/kg (n = 12), 2.5 mg/kg (n = 12), and 3.3 mg/kg (n = 12) but also included select information for the other doses.

Across all doses, the median exposure to TUB-040 was 161 days, and only a minority (n = 15; 22%) had discontinued treatment. The main causes of treatment discontinuation were disease progression (n = 13) and adverse events (n = 2).

Across all dose cohorts (n = 67), the median age was 62 years (range, 34.0-81.0). The ECOG performance status was 0 (55.2%) and 1 (44.8%), and the time from first diagnosis was a median of 5.3 years. Patients had received a median of 4 prior lines of therapy (range, 1-7). Most patients had prior exposure to bevacizumab (83.6%; Avastin) and a PARP inhibitor (76.1%), with 13.4% of patients also having received prior mirvetuximab soravtansin (Elahere). The median H score for NaPi2b expression was 175 (range, 95-295).

The median follow up was 7.8 months (range, 1.0-19.2), and confirmed ORRs were 40%, 58%, 58%, and 42% at the 1.67, 2.1, 2.5, and 3.3 mg/kg doses, respectively. The ORR in each group consisted primarily of partial responses, except for 1 confirmed complete response at the 2.5 mg/kg dose. The CA125 response rate was 81%.

More than half of patients (56.2%) remained free of a PFS event across the 1.6, 2.0, and 2.4 doses. Efficacy data in the 3.3 mg/kg were not yet fully mature, González-Martín noted in his slides. Of the 4 patients who received mirvetuximab soravtansin, there were 2 partial responses to the 2.1 mg/kg dose and 2 patients with stable disease in the 3.3 mg/kg arm.

Activity was also seen across those with high and low levels of folate receptor alpha expression.

All patients enrolled in the study experienced a treatment-emergent adverse events (TEAE). In the 46 patients receiving the dose of 1.67 to 3.3 mg/kg, the rate of grade 3 or higher TEAE was 35%. The grade 3 or higher TEAE rate was 49% across the full cohort of the study (N = 67).

Grade 3 or higher serious TEAEs were experienced by 15% of patients in the 1.67 to 3.3 mg/kg dose group and were seen in 21% of those enrolled across the full study. Dose-limiting toxicity was observed at the 5.3 mg/kg dose. The maximum tolerated dose was determined to be 4.4 mg/kg. The phase 2a portion of the study will be focused on further dose optimization.

The most common TEAE were nausea (78.3%), fatigue (47.8%), neutropenia (41.3%), anemia (34.8%), diarrhea (32.6%), constipation (32.6%), decreased appetite (28.3%), vomiting (26.1%), alopecia (26.1%), abdominal pain (26.1%), and urinary tract infection (21.7%). These events were mostly grade 1/2 in severity. Grade 3/4 TEAEs included neutropenia (21.7%), anemia (8.7%), thrombocytopenia (4.3%), nausea (4.3%), constipation (2.2%), and abdominal pain (2.2%).

“There were no clinically relevant bleeding, pneumonitis, ocular toxicity, stomatitis, or neuropathy,” González-Martín noted. The only major ocular TEAE was dry eye, which was seen at a rate of 13%. Antiemetic therapy was not required at the outset of the study, he noted.

There were 2 cases of asymptomatic transient pneumonitis that occurred at dose levels 1.67 mg/kg and 2.1 mg/kg. These each were grade 1 in severity and resolved without issues. “Both were short and resolved without treatment discontinuation,” González-Martín said.

In June 2024, TUB-040 received a fast track designation from the FDA for platinum-resistant ovarian cancer, based on early promise demonstrated for the agent.² Tubulis noted plans to initiate additional studies, based on the early results presented at the ESMO meeting. They indicted plans to present data on the NSCLC cohort of the study at a future medical meeting.³

References

1. González-Martín A, Sehouli J, Braicu EI, et al. NAPISTAR 1-01: A phase I dose escalation study of TUB-040, a novel NaPi2b-targeting exatecan antibody-drug conjugate (ADC) in patients with platinum-resistant ovarian (PROC) high grade serous carcinoma (HGSC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA43.
2. Tubulis receives FDA fast track designation for antibody-drug conjugate candidate TUB-040 in platinum-resistant ovarian cancer. News release. Tubulis. June 27, 2024. Accessed October 19, 2025. https://tubulis.com/news/tubulis-receives-fda-fast-track-designation-for-antibody-drug-conjugate-candidate-tub-040-in-platinum-resistant-ovarian-cancer/
3. Tubulis Presents First Clinical Data from Phase I/IIa Trial for TUB-040 in Platinum-Resistant Ovarian Cancer (PROC) at ESMO 2025. News release. Tubulis. October 19, 2025. Accessed October 19, 2025. https://tubulis.com/news/tubulis-presents-first-clinical-data-from-phase-i-iia-trial-for-tub-040-in-platinum-resistant-ovarian-cancer-proc-at-esmo-2025/