In the phase 1/2a NAPISTAR 1-01 trial (NCT06303505), the NaPi2b-targeting antibody-drug conjugate (ADC) TUB-040 showcased significant durable efficacy with a manageable safety profile in heavily pretreated patients with platinum-resistant ovarian cancer, according to Toon Van Gorp, MD, PhD.1
Data shared at the 2026 ASCO Annual Meeting (ASCO 2026) indicated that TUB-040 elicited a confirmed objective response rate (ORR) of 58.2% (95% CI, 45.5%-70.2%) in evaluable patients (n = 67). Across doses of 1.67 mg/kg to 3.3 mg/kg, the confirmed ORR was 61% (95% CI, 45.4%-74.9%). When broken down by dose level, confirmed ORRs were 70%, 58%, 68%, and 50% in the 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) cohorts, respectively. Moreover, the median progression-free survival (PFS) was 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 responses ongoing beyond 6 and 12 months, respectively.
“The median PFS for the whole population was 11 months, which is very high. When we look at the recently published phase 3 studies, KEYNOTE-B96 [NCT05116189], the ROSELLA study [NCT05257408], and the MIRASOL study [NCT04209855], they all have a PFS below 8.3 months, so this is a really remarkable result,” Van Gorp said in an exclusive interview with OncLive®. “The DOR was also very long; the median DOR was NR after a median follow-up of 8.7 months. This means not only do we have a high ORR, but when patients do respond, they stay on the drug for a very long time.”
Previous data from NAPISTAR-1-01 were shared during the 2025 ESMO Congress. At dose levels ranging from 1.67 mg/kg to 3.3 mg/kg, the ORR was 59% and the disease control rate was 96%.2 The confirmed ORR was 50%, with responses still ongoing for 93% of patients at the time of the presentation.
In the interview, Van Gorp discussed the design of NAPISTAR 1-01, safety findings with the ADC across examined dose levels, and efficacy data presented during ASCO 2026. 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.
OncLive: What was the rationale for developing TUB-040, a NaPi2b-targeted ADC, in platinum-resistant ovarian cancer?
Van Gorp: The NAPISTAR 1-01 study is a phase 1 study with TUB-040. TUB-040 is an ADC targeting NaPi2b, a sodium-phosphate channel in cells that is very prevalent in ovarian cancer, [making it] an ideal ADC target. That's why we started with the phase 1 study, first with dose escalation. The study is now continuing into the dose-expansion parts.
How was the phase 1/2a NAPISTAR 1-01 trial of TUB-040 designed, and what end points were evaluated?
This is a phase 1 study, so the primary end point is safety. We wanted to determine the maximum tolerated dose of TUB-040. We had different dose steps going from 0.5 mg/kg up to 5.3 mg/kg, and we eventually reached the maximum tolerated dose at 4.4 mg/kg. We then looked at 4 different dose levels, going from 1.67 mg up to 3.3 mg/kg; these were the doses of interest where we took a deep dive during the presentation, looking at [both] safety and efficacy in these patients.
What were the primary adverse effects seen with TUB-040?
TUB-040 in Platinum-Resistant Ovarian Cancer: Key Highlights
- TUB-040 induced a confirmed ORR of 58.2% (95% CI, 45.5%-70.2%) in 67 evaluable patients, with clinically meaningful responses observed across doses ranging from 1.67 mg/kg to 3.3 mg/kg.
- The median PFS reached 11.0 months (95% CI, 7.5-NA), with 71% and 50% of patients free of disease progression at 6 and 12 months, respectively.
- Hematologic toxicity was mostly grade 1/2 in the lower dose cohorts, with low rates of treatment discontinuation.
This is an ADC with a topoisomerase 1–inhibiting payload, so typically you see hematologic toxicity such as anemia, neutropenia, and thrombocytopenia, [along with gastrointestinal toxicity] like nausea and vomiting. Something special about TUB-040 is it's a very safe and stable ADC. What we saw was mainly grade 1/2 [toxicity]; when we went up to higher dose cohorts, we saw some grade 3/4 [events], but in the lower [dose] cohorts there was almost no grade 3/4 toxicity, and yet we still saw very good efficacy. That's why these dose levels, with a low dose, good efficacy, and very low toxicity, are so interesting to continue [to explore].
Was TUB-040's activity dose dependent?
No, it was not really dose-dependent. As soon as we got to 1.67 mg/kg, the [ORR], [which is] our efficacy measure, was very stable. In the total population, the confirmed [ORR] was 58%, which is very high, and in the dose levels of interest it was 61%. This was very stable across the 4 different dose levels of interest, all with very consistent [ORRs]. That's why the dose level we're [continuing into] phase 3, and for accelerated approval, is 2.1 mg/kg, a fairly low dose that still [shows] this very nice activity.
How quickly did patients respond to TUB-040 in NAPISTAR 1-01?
We didn't show this in the presentation, but the time to response was very fast. Most patients have a response after the first or second evaluation. You also see it when you start treating these patients: CA-125, a tumor marker, just drops immediately, and it's remarkable [how consistently] we saw this drop across almost all patients. It's really encouraging, [because] you can show this to the patients immediately and [they] immediately see there's a result.
