BC3195, a novel ADC targeting cadherin-3 (CDH3): Preliminary results of a phase I study in patients with advanced solid malignancies (study BC3195-102).

3035 Background: Cadherin-3 (CDH3), a calcium-dependent adhesion glycoprotein, is overexpressed on lung, breast, ovarian, colorectal, pancreatic, head-neck and other malignancies, but expression on nonmalignant tissue is negligible. CDH3 is essential for cancer cell proliferative signaling and is associated with aggressiveness, invasiveness and poor prognosis. BC3195 is an antibody-drug conjugate (ADC) comprised of an antibody targeting CDH3, a cleavable linker and a monomethyl auristatin E (MMAE) payload. Methods: Two phase Ia/Ib studies of BC3195, whose objectives are to evaluate the safety, pharmacokinetics (PK) and preliminary antitumor activity of the ADC, are enrolling patients (pts) with advanced solid malignancies in the US (BC3195-102) and China (BC3195-101). In both studies, BC3195 is administered as a 1-hour (h) IV infusion every 3 weeks. In BC3195-102, dose escalation uses a BOIN design with pre-selected dose levels (DLs) of 1.8 and 2.4 mg/kg and an algorithm to explore lower or intermediate DLs based on safety. Results: As of data cut-off (Dec 30, 2025), 16 pts have been enrolled at DLs of 1.2 (3 pts), 1.5 (3 pts), 1.8 (9 pts), and 2.4 mg/kg (1 pt). Fourteen (87.5%) pts had received ≥3 prior treatment. Fatigue (81.3%) and stomatitis (62.5%) were the main adverse events (AEs). Three pts (18.8%) had Grade ≥3 AEs, two of which were Grade 3 stomatitis in the first week post-treatment of Cycle 1 at the 1.8 mg/kg DL of Cohort 1. The dose of BC3195 was subsequently de-escalated to 1.2 mg/kg and then re-escalated to 2.4 mg/kg along with preventative measures, which included ice chip mouth rinses, dexamethasone mouthwash, and B vitamins in the peri-treatment period, and topical steroids for any skin rash. There was no further stomatitis of Grade 3 severity after implementation of these measures; 1 pt had a Grade 3 rash in Cycle 2 at 1.5 mg/kg that responded rapidly to oral steroids. Neither ocular nor neurotoxicity have been noted. Of 16 pts evaluable for tumor response (RECISTv1.1), 3 partial responses occurred in heavily pretreated pts with HER+ breast cancer, prostate cancer, and fibrosarcoma, all of whom were treated at the 1.8 mg/kg DL. Preliminary PK results (1.2-1.8 mg/kg) include med T max values of 1 h for both ADC and total antibody (TA), whereas med T max values for free MMAE range from 65 to 89 h. At 1.8 mg/kg, mean t 1/2 values are 58 h, 92 h, and 95 h for the ADC, TA and MMAE, respectively. ADC exposure has been highest at 1.8 mg/kg, with mean C max and AUC last values of 31.8 μg/mL and 1297 μg*h/mL, respectively. Conclusions: BC3195 has a manageable safety profile, favorable PK characteristics and demonstrated preliminary antitumor activity in several types of heavily pretreated advanced solid malignancies. Based on shared safety data, enrolment in both BC3195-102 (US) and BC3195-101 (China), which is in dose expansion, is converging on the 2.1 mg/kg DL (NCT06548672). Clinical trial information: NCT06548672 .