1315P - BC3195, a novel ADC targeting CDH3: Preliminary results of a first-in human phase I study in patients with advanced solid malignancies

Background

Cadherin-3 (CDH3), a calcium-dependent cell-cell adhesion glycoprotein, is overexpressed on lung, breast, ovarian, colorectal, pancreatic, head and neck and other malignancies, but with negligible expression on nonmalignant tissues, and associated with cancer aggressiveness, invasiveness, and poor prognosis. BC3195 is known as the only ADC in clinical stage, targeting CDH3 with payload of MMAE.

Methods

A phase I, open-label, first in human study to evaluate the safety, tolerability, PK, and preliminary antitumor activity of BC3195 is being performed in patients(pts) with advanced solid malignancies. Tumor assessments are performed every 6 weeks using RECIST v1.1. BC3195 is administered as 1 hour (h) IV infusion every 3 weeks. An evaluation of seven dose levels (DLs) is planned: 0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 3.6 mg/kg with a BOIN design guiding dose escalation.

Results

As of the data cut-off-date (April 28, 2024), twenty pts (median age, 59.5; male, 70%) have been enrolled, with 3 pts each in the 0.3, 0.6, 1.2 and 1.8 mg/kg DLs, and 8 pts in the 2.4 mg/kg DL. All of the pts were DLT evaluable, and only one DLT event (Grade 3 pharyngitis) occurred in the 2.4 mg/kg DL. Rash, stomatitis and liver function test elevations were the main adverse events (AEs), most AEs were grade 1 or 2 in severity and manageable. Fifteen pts were evaluable for tumor assessment, one unconfirmed PR was reported with target lesion shrinkage by 64.7% in a NSCLC pt in the 2.4mg/kg DL who harbored EGFR T790M mutation and progressed after 5 lines of prior treatment, 7 pts showed stable disease as the best response. PK results showed that exposure for the ADC, total antibody (TA) and MMAE increased with dose up to 2.4 mg/kg. ADC and TA basically exhibited linear PK characteristics, while MMAE showed non-linear PK. Free MMAE was highest at the 2.4 mg/kg DL with average C_max 8.2 ng/ml and AUC_0-last 1481ng*h/ml. Median T_max values for ADC and TA were 1 h, and median T_max for free MMAE was 25-169 h.

Conclusions

BC3195 exhibited favorable safety profile and PK characteristics up to 2.4mg/kg. Given BC3195’s safety and PK behavior, as well as preliminary activity at the 2.4 mg/kg DL, patient enrollment at higher dose levels is ongoing. Clinical trial information: NCT05957471.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Biocity Biopharmaceutics Co., Ltd.

Funding

Biocity Biopharmaceutics Co., Ltd.

Disclosure

S. Wang, H-J. Guo, L-Q. Zhang, I.Y. Wang, Y.J. Hei: Financial Interests, Personal, Full or part-time Employment: Biocity Biopharmaceutics Co., Ltd. All other authors have declared no conflicts of interest.