Abstract
Background – IB6 expression is low in healthy epithelial tissues and elevated in several tumors, including NSCLC, making it a promising drug delivery target. Sigvotatug vedotin, an investigational IB6-directed antibody-drug conjugate, has shown encouraging activity in NSCLC. Preliminary real-world IB6 expression pattern data were previously presented. This updated analysis with a larger cohort characterizes NSCLC tumors at different IB6 expression levels with associated patient characteristics.

Methods – This retrospective observational study used deidentified real-world clinical and molecular data from US patients with mNSCLC in the Tempus database. Patient characteristics were obtained via electronic health record integration and abstraction. Eligible patients had given consent for tumor samples, which were collected after May 1, 2019, from primary or metastatic lesions and met key criteria regarding biopsy and tumor content. IB6 expression was determined by immunohistochemistry (IHC) at a central lab. IB6-expressing tumors had ≥1% of tumor cells with any staining intensity. IB6-high tumors had ≥50% of tumor cells with staining at IHC ≥2+ intensity.

Results – In a 253-patient cohort, median age was 67 years. Overall, 51% were male, 56% were White, 80% received treatment at academic sites, 87% had stage III or IV disease at diagnosis, and 69% had nonsquamous histology. Of the tissue samples, 63% were from metastatic lesions, and 83% were taken on or after the diagnosis of metastatic disease. In the 227 patients with known IB6 IHC expression, 93% (95% CI, 89%–96%) of patients had IB6 expression on ≥1% of tumor cells with no significant difference by histology. IB6-high expression was observed in 77% (95% CI, 71%–82%) of samples and significantly varied by histology (81% [95% CI, 74%–87%] in nonsquamous samples and 57% [95% CI, 41%–72%] in squamous samples). Time between biopsy collection and staining (<5 vs ≥5 years) did not impact prevalence.

Conclusions – This is an updated analysis of the first real-world study characterizing IB6 expression in mNSCLC. While the clinical implications of IB6 remain under investigation, these data suggest that IB6 may be a widely applicable therapeutic target, which warrants further exploration.

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