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).

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)