BC3195 Phase 1 Study Shows Promising ORR in NSCLC and EGFRmut NSCLC: ESMO 2024

On September 14, 2024, BioCity unveiled interim clinical findings for its pioneering antibody-drug conjugate (ADC), BC3195, targeting CDH3 (P-Cadherin) at the European Society for Medical Oncology (ESMO) Congress 2024. These preliminary results highlight the safety and efficacy of BC3195 in a Phase I clinical trial involving patients with advanced non-small cell lung cancer (NSCLC).

As of August 10, 2024, BC3195 has shown notable antitumor activity in patients with advanced NSCLC, achieving an objective response rate (ORR) of 36.4%, with 4 out of 11 patients responding to the treatment. The response was particularly impressive in patients with epidermal growth factor receptor mutations (EGFRmut), where the ORR was 80% (4 out of 5 patients). The drug also exhibited manageable safety and tolerability profiles, along with favorable pharmacokinetic properties. Efforts to optimize dosage and recruit more patients with NSCLC, breast cancer, and other CDH3-expressing cancers are ongoing, with the clinical trial registered under NCT05957471.

The trial has enrolled 34 patients, with a median age of 59.5 years, and 64.7% of them being male. Patients received varying doses of BC3195: 3 patients each at 0.3, 0.6, 1.2, and 1.8 mg/kg administered intravenously (IV) every 3 weeks (Q3W), 21 patients at the 2.4 mg/kg IV Q3W dose level, and 1 patient at the 1.2 mg/kg IV weekly dose level.

In terms of safety, all patients participating in the dose-escalation phase of the study were assessed for dose-limiting toxicity (DLT). One patient experienced Grade 3 pharyngitis, a DLT, while on the 2.4 mg/kg IV Q3W dose. Common adverse events (AEs) included rash, stomatitis, and liver function abnormalities, with most cases of rash and stomatitis occurring during the first cycle and being manageable. Fourteen patients (41.2%) encountered Grade 3 or higher treatment-related adverse events (TRAEs), with stomatitis (23.5%), neutropenia (8.8%), and rash (8.8%) being the most frequent.

Efficacy results were also promising. Five patients, including 4 with NSCLC and 1 with breast cancer, achieved confirmed partial responses (PRs) after treatment with the 2.4 mg/kg IV Q3W dose. Among 11 NSCLC patients treated at this dosage, 10 showed reductions in tumor volume, with 4 confirmed PRs and 6 achieving stable disease (SD) as their best response. The ORR and disease control rate (DCR) at this dose were 36.4% and 90.9%, respectively. Notably, 80% of EGFRm NSCLC patients had confirmed PRs. However, no complete responses (CRs) or PRs were recorded at doses up to 1.8 mg/kg IV Q3W among the 30 patients evaluated for tumor response.

BioCity plans to continue its collaboration with global researchers to further the clinical development of BC3195, encouraged by these promising results.

BC3195 is currently the only ADC targeting CDH3 (P-Cadherin) in global clinical development. Preclinical studies demonstrated that BC3195 binds strongly to membrane CDH3 and is efficiently internalized. It incorporates a clinically validated, cleavable linker and payload (vc-MMAE), enabling the destruction of both targeted cancer cells and surrounding cells, an effect known as the bystander effect. In animal models, BC3195 showed a favorable safety profile and robust antitumor activity, with tumor growth inhibition rates exceeding 100% in certain cases.

BioCity, founded in December 2017, is a clinical-stage biopharmaceutical company dedicated to developing novel therapeutics for cancer and autoimmune disorders. With a diverse pipeline of over 10 innovative drug candidates, BioCity is advancing five core oncology assets through Phase 1/2 clinical development, including first-in-class CDH3 and GPC3-targeting ADCs, WEE1 and ATR inhibitors, and a monoclonal antibody targeting TIM-3 in collaboration with AstraZeneca. Additionally, BioCity's SC0062, a highly selective ETA antagonist, is in Phase 2 development for chronic kidney disease (CKD), with plans for a global Phase 3 registration trial.