IBI354 Shows promise in Treating HER2-Positive Breast Cancer: ASCO 2025 Update

Chicago, IL – Updated findings from a phase 1 clinical trial, presented at the 2025 ASCO Annual Meeting, reveal that the novel antibody-drug conjugate (ADC) IBI354 demonstrates both safety and meaningful antitumor activity in patients with pretreated HER2-positive advanced breast cancer. The data offers a beacon of hope for individuals with limited treatment options for this aggressive form of cancer.

IBI354 Efficacy in HER2-Positive Breast Cancer

The trial, identified as NCT05636215, evaluated the efficacy of IBI354 in patients with HER2-positive breast cancer. The results are encouraging. Evaluable patients (n = 88) achieved an overall response rate (ORR) of 59.1% (95% CI, 48.1%-69.5%). This included a complete response rate of 4.5% and a partial response (PR) rate of 54.5%. The stable disease (SD) and progressive disease (PD) rates were 31.8% and 9.1%, respectively. The disease control rate (DCR) was a notable 90.9% (95% CI, 82.9%-96.0%).

Did You Know? The five-year survival rate for metastatic HER2-positive breast cancer has considerably improved over the past two decades, rising from approximately 20% to over 40%, thanks to targeted therapies like trastuzumab and pertuzumab, according to a 2023 report in the journal *Targeted Oncology*.

Notably, in a subset of patients with HER2-positive breast cancer treated with IBI354 at a dose of 9 mg/kg once every 3 weeks (n = 29), the ORR climbed to 72.4% (95% CI, 52.8%-87.3%), comprised exclusively of PRs. The SD and PD rates were 17.2% and 10.3%, respectively, and the DCR was 89.7% (95% CI, 72.6%-97.8%).

Safety Profile of IBI354

The safety population of the trial (n = 368) included patients with breast cancer and other HER2-positive solid tumors. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.6% of patients, and 39.1% of patients experienced grade 3 or higher TEAEs. The rates of any-grade and grade 3 or higher treatment-related AEs (TRAEs) were 90.8% and 27.4%, respectively. Serious AEs and treatment-related serious AEs occurred at rates of 20.7% and 9.0%, respectively.

TEAEs led to treatment interruption,treatment reduction,and treatment discontinuation in 26.9%, 2.7%, and 1.9% of patients, respectively. One patient (0.3%) died due to TEAEs, but no deaths were attributed to TRAEs.Treatment-related interstitial lung disease was reported in 1.9% of patients.

Pro Tip: Patients undergoing treatment with IBI354 should be closely monitored for any signs of adverse events, notably respiratory symptoms, and should promptly report any concerns to their healthcare provider.

IBI354: Mechanism of Action

IBI354 is a novel ADC composed of trastuzumab (Herceptin) conjugated to a camptothecin derivative. Its mechanisms of action include selective binding of the antibody to the tumor, internalization of the agent, lysosomal degradation, release of the cytotoxic payload, inhibition of topoisomerase 1 activity to induce DNA damage and cell apoptosis, and a bystander effect to kill neighboring cancer cells.

Trial Design and Patient Population

The global, multicenter, phase 1 study enrolled patients with advanced breast cancer and other solid tumors with HER2 expression or gene alterations who had progressed on or were intolerant to standard therapies. Breast cancer patients needed to have a HER2 expression of immunohistochemistry (IHC) 2+/in situ hybridization+ or IHC 3+.

Enrolled patients received IBI354 at doses ranging from 0.8 mg/kg to 18 mg