Novel PTK7-Targeted Antibody–Drug Conjugate Shows Activity in Advanced Solid Tumors.

A first-in-human, open-label, phase 1a/b trial evaluated DK210-ADCS, a PTK7-targeted antibody–drug conjugate (ADC) delivering exatecan, in adults with advanced solid tumors refractory to standard therapy. PTK7 (protein tyrosine kinase 7) is a transmembrane protein overexpressed in multiple cancers, including triple-negative breast, ovarian, and non–small-cell lung cancers (NSCLC).

The study enrolled 110 patients (median age, 61 years; 70% female; median 4 prior systemic therapies). Phase 1a established the recommended phase 2 dose (RP2D) at 6.4 mg/kg every 3 weeks, with dose-limiting toxicities of grade 3 neutropenia and diarrhea. The most common treatment-related adverse events (TRAEs) included nausea (61%), fatigue (49%), and decreased appetite (38%); grade ≥3 TRAEs occurred in 40% of patients, mainly neutropenia (18%) and anemia (9%).

In phase 1b efficacy analysis at RP2D (n=42), the objective response rate (ORR) was 24%, including partial responses in heavily pretreated triple-negative breast cancer (TNBC), epithelial ovarian cancer, and NSCLC. Median duration of response was 5.8 months, and disease control rate (DCR) reached 62%.

Preliminary biomarker analysis suggested higher response rates in tumors with strong PTK7 expression, supporting its role as a predictive biomarker. The safety profile was considered manageable with supportive care and dose adjustments.

The investigators conclude that DK210-ADCS warrants further study in tumor-specific expansion cohorts and combination regimens, given its targeted mechanism and early efficacy signals in refractory settings.

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