An exploratory clinical study investigating the neoadjuvant treatment of HER2-low expressing, stage II-III breast cancer with disitamab vedotin combined with penpulimab (RCVDBCIIR005).

e12620 Background: HER2-low expressing breast cancer represents a heterogenous subtype with limited targeted therapeutic options. Disitamab Vedotin, a novel HER2-targeted antibody-drug conjugate (ADC), and Penpulimab, an anti-PD-1 monoclonal antibody, have both demonstrated potential in various cancer treatment contexts. This study aims to assess the clinical efficacy and safety of Disitamab Vedotin in combination with Penpulimab as neoadjuvant therapy in patients with HER2-low expressing, stage II-III breast cancer. Methods: This single-center, prospective, non-randomized clinical trial enrolled patients with newly diagnosed HER2-low expressing (IHC 1+ or 2+ without amplification by FISH), stage II-III breast cancer in West China Hospital. All patients received neoadjuvant treatment with Disitamab Vedotin (2.0 mg/kg IV) and Penpulimab (200 mg IV) every 3 weeks for a total of 6 cycles, followed by surgery. The primary endpoint was pathological complete response (pCR), and secondary endpoints included overall response rate (ORR) and treatment-related adverse events (AEs). Results: From August 2023 to August 2024, a total of 20 patients were enrolled in the study, with two patients withdrawing due to intolerance to adverse reactions and two others discontinued due to disease progression. At the end of the treatment, the total pCR (ypT0/is ypN0) rate was 25.0% (4/16). The ORR reached 56.3% (9/16) by the clinical response assessment at the end of neoadjuvant treatment. The PD-L1 positive subgroup demonstrated a higher tpCR rate compared to the PD-L1 negative subgroup (33.3% vs. 14.3%). Additionally, the IHC 1+ subgroup exhibited a lower tpCR rate than the IHC 2+ subgroup without amplification by FISH (11.1% vs. 42.9%). The most common AEs were constipation (43.8%) and itching (37.5%), with one reported serious adverse event (SAE) of herpes zoster, and no significant toxicities or treatment-related deaths observed. Conclusions: While the clinical benefit may be somewhat limited, the combination of Disitamab Vedotin and Penpulimab as neoadjuvant treatment for HER2-low early or locally advanced breast cancer demonstrates manageable safety and potential for furtheroptimization. This warrants additional investigation to refine and optimize treatment strategies. Clinical trial information: NCT05726175 .