ESMO 2025 | NAPISTAR 1-01: TUB-040 in platinum-resistant ovarian high-grade serous carcinoma

Well, the NAPISTAR 1-01 study was a first-in-human study, Phase I/IIa, with a new ADC, with an exatecan payload and a very stable linker providing a DAR of 8 targeting NaPi2b. NaPi2b is a protein transporter highly expressed in ovarian cancer. This new ADC has a couple of things that are relatively important or I would say mostly important for the interpretation of the findings. One is the silencing and the other is the linker; the linker is a new technology, a site-specific taken platform that provides a very stable join of the payload and the linker, so there is less release of the drug before the ADC is targeting the tumor. In summary, what we have done is a Phase I study. We have presented the data of the platinum-resistant ovarian cancer patients. Patients with up to seven prior lines were included, five platinum, two non-platinum. The primary endpoint was safety, tolerability, as well as MTD. And secondary endpoints were response rate, duration of response, as well as disease control rate. We have included a total of 67 patients. We have dosed them from 0.5 to 5.3. And the focus of the presentation was the 1.67 to 3.3 mg per kg steps. It’s important to remark that the population was heavily pretreated, a median of four prior lines. Most of the patients, 85% have already received Bevacizumab. 74% have already received PARP inhibitor, which is a population that we usually see, at least in our context. Well, the results. Maximum tolerated dose was 4.4. What we have presented is the data of safety for the overall population, but with the focus on the dose below 4.4, which was from 1.67 to 3.3. We have to say that the drug is tolerable. The safety profile was excellent. Rate 3 or higher safety of treatment-emerging adverse events was 35%. 20% meets dose reduction in this range of 1.67 to 3.3 with no discontinuation due to adverse events. Most common adverse events were nausea, fatigue, but mostly grade 1 or 2, and in terms of hematological toxicity, it was also mainly low-grade and manageable with grade 3 or higher neutropenia, anemia, and thrombocytopenia of 22, 9, and 4 percent of the patients. It is remarkable that only two asymptomatic grade 1 pneumonitis were observed, and there was no need to discontinue the treatment because it solved in both cases, and it is also important to highlight that we have not observed ocular toxicity, stomatitis, significant pneumonitis, neuropathy, or bleeding. So this is a very well-tolerated ADC. In terms of efficacy, we have confirmed a 50% response among the 59% of unconfirmed response that we have already provided, which is important. We started to see responses since the very beginning with 1.67 mg per kg, and across all these doses, the unconfirmed overall response rate was from 50 to 67%. It’s quite high. It is also remarkable that the responses were very, very soon, and depending on the data that we will present in future events, in future conferences, and for me, it’s also very important to say that 93% of the patients that responded are still on treatment, and that 80% of the whole population treated are still on treatment as well. So that suggests that the effect of this ADC of TUB-040 is really durable. So in summary, we can say that TUB-040 is a new ADC, targeted at NaPi2b, with a very good safety profile. Most of the safety issues were low-grade and manageable. No significant ILD, no significant bleeding, no significant ocular toxicities, no significant stomatitis. So it’s a good, tolerated drug for our patients. And it is active with a high response rate of 59% and 50% confirmed response rate that most of them seem to be durable, and that’s why we are now starting the randomized dose optimization phase because we are convinced that TAF40 is an excellent candidate to be developed in the platinum-resistant ovarian cancer setting.

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