NAPISTAR-1-01 Data Support Rapid TUB-040 Development in Biomarker-Unrestricted Ovarian Cancer

Responses to the NaPi2b-targeting antibody-drug conjugate (ADC) TUB-040 did not differ by NaPi2b expression level in patients with platinum-resistant ovarian cancer enrolled in the phase 1/2a NAPISTAR 1-01 trial (NCT06303505), supporting a biomarker-unrestricted development path, according to Toon Van Gorp, MD, PhD.¹

“I think this means we don't have to test. [NaPi2b] is expressed in more than 95% of ovarian cancers, so probably we don't have to test at all. This is different when we look at other diseases like lung cancer, [where we're] also running a trial,” Van Gorp noted. “There, the biomarker is probably important, because we see a clear difference between the high expressers and the low expressers, [with high] expressers having a better response. So, it's not the same for [every] disease, but for ovarian cancer, I'm pretty sure we don't have to test.”

Additional findings from the trial, which were presented during the 2026 ASCO Annual Meeting (ASCO 2026) showed that TUB-040 induced a confirmed objective response rate (ORR) of 58.2% (95% CI, 45.5%-70.2%) in 67 evaluable patients with a median progression-free survival (PFS) of 11.0 months (95% CI, 7.5-not available [NA]). The median duration of response (DOR) not yet reached (NR; 95% CI, 8.5-NA) with 79% and 57% of patients experiencing responses that extended beyond 6 and 12 months, respectively.

In the second part of an exclusive interview with OncLive^®, Van Gorp underscored the promise of TUB-040 in platinum-resistant ovarian cancer, teased the next steps for its development, and detailed the significance of NAPISTAR 1-01. Van Gorp is a professor of gynecologic oncology at the University of Leuven and lead of the department of gynecologic oncology at Leuven Cancer Institute in Belgium.

Part 1 of this interview covers the design of NAPISTAR 1-01, safety findings with the ADC across examined dose levels, and efficacy data presented during ASCO 2026.²

OncLive: What stands out about TUB-040's safety profile and NaPi2b biomarker data?

Van Gorp: The most important thing to emphasize is this is really one of the safest ADCs I know, due to the stability of the payload and the linker. The linker stability is excellent, and that's why we have this very wide therapeutic window and can go [to lower doses] and still have this efficacy. The second thing is the biomarker: NaPi2b is very prevalent in ovarian cancer, and what we showed in the analysis is it doesn't matter whether you have high or low expression of NaPi2b. The responses were almost equal in the high expressers and the low expressers, [meaning] this is a drug that can be used irrespective of NaPi2b expression.

What are the next steps for TUB-040 development in platinum-resistant ovarian cancer?

The next step will be to do a large phase 2 trial for accelerated approval, [which is] what they're working on, [along with] a phase 3 trial in platinum-resistant ovarian cancer. Something else that's very important is that because the safety is very good, [with] not a lot of grade 3/4 toxicity, we might be able to combine it with other chemotherapies like carboplatin. This is something we'll look at in the future in a phase 1 [combination] study, because [in my opinion] this is one of the ADCs with [real] potential for combination.

As the platinum-resistant setting continues to evolve, what do you imagine the new standard comparator will be?

I think the comparator will be one of these new regimens: the phase 3 KEYNOTE-B96 trial [NCT05116189] with pembrolizumab [Keytruda], relacorilant [Lifyorli] together with nab-paclitaxel [Abraxane], [or] mirvetuximab soravtansine-gynx [Elahere]. I think these are the three combinations or drugs that have shown the potential to be better than single-agent chemotherapy.

This means, in my opinion, future studies can [no longer] compare against single-agent chemotherapy; we have a new standard of care, and it's one of these three regimens. We don't have any comparison between [them], so we don't know which one is best, but these are three potential treatments for our patients, and they should be in the control arm or in the inclusion-exclusion criteria of the studies; so patients should have received one before they can enter a study if [it isn't used as the] comparator.

What were the most significant gynecologic oncology abstracts shared at ASCO 2026?

I think the [NAPISTAR 1-01] study is potentially one of the most important abstracts, not because I presented it, but because of the data. This is an ADC with one of the highest ORRs, an unprecedented median PFS, and a very durable, long duration of response, so I think this is one of the ADCs to look out for in the future and a very important competitor to the other ADC[s out there].

If I have to choose another study, I'd say the MIROVA study [NCT04274426],³ which was actually a negative study combining mirvetuximab soravtansine with carboplatin, then [continuing] mirvetuximab in the maintenance setting, compared with a standard chemotherapy doublet in the platinum-sensitive setting. It's a negative study, and this is something we didn't expect, because we thought combining carboplatin with mirvetuximab and continuing mirvetuximab [as] maintenance would improve the patient's prognosis. In contrast to what we thought, it's a negative study, and I think we have to do a deep dive in the future [to understand] why. [I also want to emphasize] this study because it was an academic study, not a commercial one, and academic studies are really important, too.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Van Gorp T, Sehouli J, Richardson DL, et al. NAPISTAR 1-01: results of phase 1 dose escalation of monotherapy with TUB-040, a novel NaPi2b-targeting exatecan ADC, in patients with platinum-resistant ovarian cancer (PROC). J Clin Oncol. 2026;44(suppl 16):5513. doi:10.1200/JCO.2026.44.16_suppl.5513
2. OncLive Staff. TUB-040 elicits clinically meaningful responses in heavily pretreated platinum-resistant ovarian cancer. September 16, 2026. Accessed September 21, 2026. https://www.onclive.com/view/tub-040-elicits-clinically-meaningful-responses-in-heavily-pretreated-platinum-resistant-ovarian-cancer
3. Harter P, Heitz F, Marmé F, et al. A randomized phase II trial of mirvetuximab soravtansine in folate receptor alpha (FRα)-high recurrent ovarian cancer eligible for platinum-based chemotherapy (MIROVA/AGO-OVAR 2.34). J Clin Oncol. 2026;44(suppl 16):5506. doi:10.1200/JCO.2026.44.16_suppl.5506