Background – IB6, encoded by ITGB6, is overexpressed in several solid tumors, including non-small cell lung cancer (NSCLC), making it a promising therapeutic target. Sigvotatug vedotin, an investigational IB6-directed antibody-drug conjugate, has shown encouraging activity in NSCLC (Peters, ASCO 2024). The IB6 Expression and Clinical Outcomes in NSCLC study was conducted to characterize real-world IB6 expression and its clinical relevance in patients with metastatic NSCLC (mNSCLC). We present findings, including prevalence of and characteristics associated with IB6 expression in mNSCLC, in a preliminary cohort of US patients.

Methods – This retrospective, real-world observational study used the Tempus deidentified database of patient records to examine data for patients with mNSCLC who have been sequenced and gave consent for tumor samples collected after May 2019 to be used for research purposes. Patient demographics and clinical characteristics were obtained via electronic health record integration and clinical record abstraction. Tissue samples from primary or metastatic lesions underwent IB6 immunohistochemistry (IHC) following key criteria regarding biopsy type and tumor content. IB6 expression by IHC was categorized as high or low, and patients were stratified by histology.

Results – In the preliminary cohort of 110 patients with mNSCLC, median age was 66 years. Of the patients, 53.6% were female, 47.3% were White, and 33.6% were Black or African American. Of the tissue samples, 36.4% were from primary tumors, and 72.7% had nonsquamous histology. IB6 prevalence estimates demonstrated high IB6 expression in 69.7% (95% CI, 59.6%-78.5%) of samples. IB6 expression varied by histology, with high IB6 expression in 75.0% (95% CI, 63.4%-84.5%) of nonsquamous samples and 50.0% (95% CI, 26.0%-74.0%) of squamous samples. A larger cohort of patients with accompanying full patient characteristics will be presented.

Conclusions – In this diverse patient population, high IB6 expression is common in mNSCLC, particularly in non-squamous histology, underscoring the potential of IB6 as a novel biomarker and therapeutic target. Further investigation into IB6-directed therapies is warranted.

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