Association of LIV-1 expression with clinical efficacy in patients with advanced breast cancers treated with BRY812.

e15005 Background: LIV-1 is a transmembrane protein that is involved in the transport of zinc ions across the cell membrane and exhibits metalloproteinase activity, with its expression correlated to malignant progression and metastasis in breast cancer and some other cancer types. BRY812 is the ADC targeting LIV-1 with MMAE as cytotoxic payload, which has demonstrated promising clinical improvements in patients with advanced solid tumors, mainly breast cancers, in an ongoing multicenter, open-label, phase I clinical study. Here is the retrospective analysis of LIV-1 and clinical efficacy from this study. Methods: From the dose escalation phase of this study, tumor samples were collected, formalin-fixed paraffin-embedded, sliced and immunohistochemistry (IHC) stained using antibody (BRY812-5) through Ventana platform to evaluate the LIV-1 expression. H-score, TPS, PS2+ and PS3+ were generated from IHC-stained slides. LIV-1 expression and efficacy were then analyzed concurrently. Results: As of Dec 13, 2024, tumor samples from 38 breast cancer patients were stained and showed that LIV-1 is highly expressed in the tumor cells. Pathological evaluation of staining pattern showed both cell membrane and cytoplasmic staining. The staining results were then analyzed with clinical efficacy from 24 breast cancer patients. With all four methods of H-score, TPS, PS2+ and PS3+, higher LIV-1 expression was observed in patients with clinical response or disease control, while lower LIV-1 expression was observed in patients with clinical non-response or disease progression, respectively. With all ROC curves of four methods versus ORR or DCR, means of AUC were all above 0.5 (0.557 to 0.759). For ROC curve of PS2+ vs ORR, AUC was calculated as 0.759 (95% CI: 0.543 and 0.975) and highest Youden index was calculated as 0.556, respectively. These results indicate that PS2+ is a statistically indicative biomarker for ORR. Therefore, ORR of 25.0% (6/24) and DCR of 58.3% (14/24) were observed in all breast cancer patients, while ORR of 42.9% (6/14) and DCR of 78.6% (11/14) were observed in PS2+ enriched breast cancer patients. Conclusions: We demonstrated that LIV-1 is highly expressed in the tumor cells of breast cancer patients. Expression level of LIV-1 (PS2+) is a statistically indicative biomarker for ORR treating with BRY812. Breast cancer patients with higher LIV-1 expression are expected to have better clinical outcome from BRY812 treatment. Clinical trial information: NCT06038058 .