Efficacy and safety of recombinant humanized anti-HER2 antibody-MMAE conjugate (RC48) in neoadjuvant for HER2-positive breast cancer: A single-arm phase II study.

e12636 Background: Breast cancer patients who achieve pCR after neoadjuvant therapy have a relatively good prognosis. Whether antibody‐drug conjugates (ADCs) can replace traditional chemotherapy combined with dual-target therapy in neoadjuvant therapy still needs to be explored. RC48 is a novel recombinant human anti-HER2 monoclonal antibody conjugated with a microtubule inhibitor (MMAE) via a cleavable linker, which can effectively kill HER2-positive tumors as well as tumors with low or heterogeneous HER2 expression through the bystander effect. The purpose of this study was to evaluate the efficacy and safety of RC48 in neoadjuvant treatment of HER2-positive breast cancer. Methods: Patients with HER2-positive breast cancer (size>20mm) or confirmed axillary lymph node metastasis were eligible and received RC48 at a dose of 2.5mg/kg alone every 2 weeks for 6 cycles followed by surgery. EC was administered postoperatively every 21 days for 4 cycles. Trastuzumab combined with pertuzumab was administered for 1 year in the adjuvant setting. The primary endpoints were ORR and pCR rates. Results: 23 patients had been enrolled, and all of them had completed surgical treatment. The median age was 45(38-70) years. The current results showed that 13.0% (3/23) achieved pCR, 78.3% (18/23) achieved PR, and 8.7% (2/23) experienced PD. The ORR was 91.3%. 42% (5/12) of patients with initially positive axillary lymph nodes turned negative after surgery. 11.8% (2/17) HR-/HER2+ patients achieved pCR. According to the proportion of target lesion reduction, patients were divided into mild response (0-50%) and moderate-to-severe response (51%-100%). In the HR-/HER2+ subtype group, 23.5% (4/17) had a mild response, and 76.5% (13/17) had a moderate-to-severe response. 6 patients with HR+ have been enrolled, and 16.7% (1/6) of them achieved pCR. All of HR+ subtypes had a moderate-to-severe response. No relevant serious (grade 3/4) toxicity has been reported. Conclusions: The present data showed an acceptable pCR rate with RC48 in HER2-positive breast cancer. Although the pCR rate was lower than the traditional chemotherapy combined with targeted therapy, the effect of rapid reduction of tumor volume was better (the moderate-severe remission rate was 82.6%). For HR+/HER2+ breast cancer, the ORR in this study reached 100%, indicating that the novel ADC had a significant inhibitory effect on the crosstalk between ER and HER2. And it was expected that the Destiny Breast 11 study would show similar results. This scheme had a good negative conversion rate for patients with positive axillary lymph nodes. Finally, RC48 provided a neoadjuvant treatment option with low toxicity and high patient compliance for HER2-positive breast cancer. Clinical trial information: NCT05134519 .