NAPISTAR 1-01: Results of phase 1 dose escalation of monotherapy with TUB-040, a novel NaPi2b-targeting exatecan ADC, in patients (pts) with platinum-resistant ovarian cancer (PROC).
Year: 2026
Type: conference-abstract
Abstract: 5513 Background: NaPi2b is overexpressed in high-grade serous ovarian cancer and non-small cell lung cancer (NSCLC). TUB-040 is a DAR8 ADC targeting NaPi2b, comprising a humanized Fc-silenced IgG1 mAb conjugated to exatecan via a cleavable, cysteine-selective, stable, solubility-mediating P5 linker providing excellent stability and biophysical ADC properties. In preclinical studies, TUB-040 induces potent antigen-specific cytotoxicity and demonstrates strong bystander activity. Methods: NAPISTAR 1-01 is a phase 1/2a study in biomarker-unselected pts with PROC and NSCLC. TUB-040 was administered Q3W in dose escalation (range 0.5-5.3 mg/kg) to pts with PROC until progression or unacceptable toxicity. Results: As of Dec 1, 2025, 67 PROC pts received TUB-040 for a median of 10 cycles (1-25), median duration of exposure was 213 days (21-546), and 42 (63%) pts were ongoing. Median age: 62 years (34-81), ECOG PS 0-1, median prior lines: 4 (1-7), prior treatment included bevacizumab (84%), PARPi (76%), and mirvetuximab soravtansine (13%). Between dose levels 1.67-3.3mg/kg (N=46), the most common all-grade TEAEs were nausea (78%), fatigue (54%), neutropenia (43.5%), anemia (37%), constipation (34%), diarrhea (33%), vomiting (28%), alopecia (28%), and decreased appetite (26%). Gr≥3 heme TEAEs by dose are in Table 1. There were no fatal TEAEs or treatment discontinuations due to TEAEs. Three pts (6.5%) experienced Gr1 pneumonitis, which resolved. Between dose levels 1.67–3.3 mg/kg, 46 pts were evaluated for efficacy. The uORR was 63% [95% CI, 47.5-77.2] and cORR was 60.9% [95% CI, 45.3-75.1] (RECIST; v1.1), including two cCRs. Responses by dose are in Table 1. The majority of responses, 90% (26/29), were ongoing. Disease control rate was 96% [95% CI, 85.2-99.5]. Among CA-125 evaluable pts (N=42), CA-125 response occurred in 81% (34/42) [95% CI, 65.6-91.5]. cORRs were similar across subgroups, including: ≥4 prior lines of therapy (cORR=71%), prior exposures to bevacizumab (62%), mirvetuximab soravtansine (63%) or PARPi (67%). Five pts with stable disease remain on treatment and eligible for response. Conclusions: TUB-040 was well tolerated with promising clinical activity at low doses, offering a potential new treatment option with a differentiated, favorable benefit–risk profile and a wide therapeutic window in PROC pts. Dose optimization is currently ongoing. Clinical trial information: NCT06303505 . 1.67 mg/kg (N=10), n (%) 2.1 mg/kg (N=12), n (%) 2.50 mg/kg (N=12), n (%) 3.3 mg/kg (N=12), n (%) Total (N=46), n (%) Complete response 1 (10) 0 1 (8) 0 2 (4) Partial response 6 (60) 7 (58) 7 (58) 6 (50) 26 (57) Stable disease 2 (20) 5 (42) 3 (25) 6 (50) 16 (35) Progressive disease 1 (10) 0 1 (8) 0 2 (4) Overall responses (PR + CR) 7 (70) 7 (58) 8 (67) 6 (50) 28 (60.9) Gr≥3 neutropenia 0 2 (17) 4 (33) 6 (50) 12 (26) Gr≥3 anemia 0 0 1 (8) 5 (42) 6 (13) Gr≥3 thrombocytopenia 0 0 1 (8) 1 (8) 2 (4)
Source: Journal of Clinical Oncology
Institutions: KU Leuven, Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie, Charité - Universitätsmedizin Berlin, OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, University of Oklahoma, King's College London, Guy's and St Thomas' NHS Foundation Trust, University of Cologne, University Hospital Cologne, Hospital Universitario Quirónsalud Madrid, Christ Hospital, Tubulis (Germany), Clinica Universidad de Navarra, Spanish Ovarian Cancer Research Group
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7162530332