BC3195, a novel ADC targeting CDH3: Preliminary results of a first-in-human phase I study in patients with advanced solid malignancies.

• DOI: 10.1200/jco.2024.42.16_suppl.e15008
• Publication Date: 2024-06-04T20:15:36Z
• Authors: Hua-Jun Chen; Sheng Wang; Rong Su; Xu-Feng Li; En-Tzu Tang; Yi-Wei Wang; Yong-Jiang Hei; Yi-Long Wu
• Keywords: Solid tumor

e15008 Background: Cadherin-3 (CDH3), a calcium-dependent cell-cell adhesion glycoprotein, is overexpressed on lung, breast, ovarian, colorectal, pancreatic, head and neck other malignancies, but with negligible expression nonmalignant tissues, associated cancer aggressiveness, invasiveness, poor prognosis. BC3195 known as the only antibody drug conjugate (ADC) in clinical stage, targeting CDH3 payload of monomethyl auristatin E (MMAE). Methods: A phase I, open-label, first human study to evaluate safety, tolerability, PK, preliminary antitumor activity being performed subjects advanced solid malignancies. Disease assessments are every 6 weeks using RECIST v1.1. administered 1 hour (h) IV infusion 3 weeks. An evaluation seven dose levels planned: 0.3, 0.6, 1.2, 2.4, 3.0 3.6 mg/kg BOIN design guiding escalation. Results: Up January st , 2024, nine patients (median age, 59; male, 56%) have been enrolled treated BC3195, each 0.6 1.2 cohorts. No DLT was observed across all Treatment emergent adverse events (TEAEs) occurring ≥3 included: aspartate aminotransferase increased (5/9, 55.6%), conjugated bilirubin triglycerides (4/9, 44%), uric acid (3/9, 33.3%), heart rate 33%), hypoalbuminemia cough 44.4%), hyponatraemia anemia asthenia rash vomiting 33.3%) back pain 33.3%). Two experienced ≥ Grade TEAEs unrelated drug. Six were evaluable for tumor assessment, (3/6, 50%) show stable disease (SD) best response (2 target lesion reduction). PK results demonstrated that exposure ADC total (TA) dose, relationship between AUC 0-last greater than dose-proportional, while C max linear. Free MMAE highest at level. Median T values TA h (end infusion), median free 25-169 h. In addition, elimination t 1/2 averaged 27-48 h, 31-68 63-76 ADC, TA, MMAE, respectively. Conclusions: exhibited favorable safety profile characteristics up 1.2mg/kg. Given BC31095’s behavior, well level, patient enrollment higher ongoing. Clinical trial information: NCT05957471 .