NaPi2b, a sodium-dependent phosphate transporter, is emerging as a promising target for platinum-resistant ovarian cancer, a setting with few effective treatments. Highly expressed in high-grade serous ovarian, fallopian tube, and peritoneal cancers—but low in normal tissue—NaPi2b is ideal for selective delivery via antibody-drug conjugates (ADCs).
Earlier NaPi2b-targeted ADCs, like lifastuzumab vedotin and upifitamab rilsodotin, showed limited benefit, but TUB-040, a next-generation ADC, has renewed interest. TUB-040 combines an Fc-silenced IgG1 antibody with the cytotoxic Topoisomerase I inhibitor exatecan via a cleavable P5 linker, improving potency, stability, and bystander effect.
In the phase 1/2a KOMET-001 trial, TUB-040 achieved a 50% overall response rate and 96% disease control, including responses at lower doses. Side effects—mostly mild to moderate—included nausea, fatigue, neutropenia, anemia, and diarrhea. With Fast Track designation from the FDA, TUB-040 may offer a significant advance for platinum-resistant ovarian cancer and potentially other NaPi2b-expressing tumors.
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