Abstract OT2-16-04: KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer: A single arm, multicenter, phase 2 study

Abstract Background: Despite the use of targeted therapy has revolutionized the treatment in the neoadjuvant setting for early, locally advanced, HER2-positive breast cancer, these approaches still have limited efficacy, which calls for persistent exploration for optimized treatment strategy. KN026 is a bispecific monoclonal antibody that targets the distinct extra-cellular domains II (Pertuzumab binding site) and IV (Trastuzumab binding site) of HER2. KN026 has better anti-tumor activity than either Trastuzumab or Pertuzumab used alone, and also aimed to demonstrate similar or better anti-tumor response than Trastuzumab in combination with Pertuzumab. Here we report the preliminary results of KN026 and docetaxel as neoadjuvant treatment in patients with HER2-positive early or locally advanced breast cancer (LABC). Methods: Treatment naive patients with HER2-positive early (T1c or 2, N1, M0; T2 or 3, N0, M0) or locally advanced breast cancer (T1c or 2 or 3, N2, M0; T3N1M0; T1c or 2 or 3, N3a or 3b, M0) were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m2 ivgtt d1, q3w) neoadjuvant treatment. The primary endpoint was total pCR rate (tpCR; defined as absence of any residual invasive cancer in the breast and lymph nodes) [ypT0/is, ypN0]). Secondary endpoints were pCR in the breast (bpCR, defined as absence of any residual invasive cancer in the breast [ypT0/is]), ORR (objective response rate), safety, PK (pharmacokinetics) and immunogenicity. The study is still ongoing, and the planned enrollment number is 30. This study is registered in ClinicalTrials.gov, number NCT04881929. The data cutoff date was April 15, 2022. Results: Between August 8, 2021, and April 15, 2022, a total of 15 patients were enrolled from 5 sites. 7 (46.7%) patients were stage II, and 8 (53.3%) patients were stage III; 12 (80%) patients with lymph node metastases, and 3 (20%) patients without lymph node metastases; 7 (46.7%) patients were hormone receptor positive, and 8 (53.3%) patients were hormone receptor negative. As of April 15, 2022, 4 patients are still under neoadjuvant therapy, 1 patient withdrew from the study earlier due to AE during neoadjuvant treatment period, and 10 patients completed the surgery. Of the 10 patients who completed surgery, tpCR rate were 50% (5/10, 95% CI: 18.7%-81.3%), bpCR rate were 50% (5/10, 95% CI:18.7%-81.3%), and ORR were 100% (10/10, 95% CI: 69.2%-100%). The incidence of TRAE and Grade ≥3 TRAEs were 100% (15/15) and 53.3% (8/15) respectively. The most common TRAE were alopecia (14/15, 93.3%), white blood cell decreased (10/15, 66.7%), anemia (10/15, 66.7%), diarrhea (9/15, 60.0%), neutrophil count decreased (9/15, 60.0%), alanine aminotransferase increased (8/15, 53.3%) and hypoalbuminemia (8/15, 53.3%). The Grade ≥3 TRAE include neutrophil count decreased (8/15, 53.3%), white blood cell decreased (5/15, 33.3%), alanine aminotransferase increased (1/15, 6.7%), and lymphocyte count decreased (1/15, 6.7%). No Grade 5 TRAEs occurred. 3 TRAEs (Alanine aminotransferase increased, blood bilirubin increased and neutrophil count decreased) leading to KN026 interruption, and no TRAE leading to KN026 discontinuation. 1 SAE (hepatitis E-not TRAE; outcome: recovered) occurred in 1 patient, without other SAE or death throughout the study. Conclusions: KN026 and docetaxel as neoadjuvant treatment has shown promising clinical benefit for patients with HER2-positive early or locally advanced breast cancer with an acceptable and manageable safety profile. Further validation in a large-scale randomized controlled trial is warranted. Citation Format: Jiong Wu, Benlong Yang, Linxiaoxi Ma, Mingliang Zhang, Kun Wang, Yiding Chen, Zhimin Fan, Jing Zhang, Summer Xia. KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer: A single arm, multicenter, phase 2 study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-16-04.