247P - KN026 in combination with docetaxel as neoadjuvant treatment for HER2+ early or locally advanced breast cancer (BC): A single-arm, multicenter, phase II study

Background

Trastuzumab (H) plus Pertuzumab (P) combined with cytotoxic agents has been the SOC for Her2+BC across perioperative to late stage. Even with high efficacy, optimized treatment strategy still needs to be explored. KN026 is a bispecific monoclonal antibody that targets domain II and IV of HER2. KN026 showed comparable or better efficacy with H+P in preclinical study. The superior efficacy had also been validated in a series of clinical trials in late line Her2+ solid tumors as well as the first-line Her2+ breast cancer and gastric cancer. Here we report the results of KN026 plus docetaxel as neoadjuvant treatment in HER2+ BC pts.

Methods

Treatment naive pts with HER2+ early or LABC were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m², ivgtt d1, q3w) as neoadjuvant treatment. The primary endpoint was tpCR rate. Secondary endpoints were bpCR, ORR, safety, etc. This study is registered in ClinicalTrials.gov, number NCT04881929.

Results

From August 9th, 2021, to July 29th, 2022, a total of 30 pts were enrolled from 5 sites. 16 pts (53.3%) were stage II, and 14 pts (46.7%) were stage III; 26 (86.7%) pts with biopsy-confirmed lymph node metastases; 15 (50.0%) pts were hormone receptor positive. As of Nov 21st, 2022, the study completed the primary outcome. 28 pts completed the surgery followed by pathological evaluation, and 2 pts discontinued from the study earlier due to AEs. In FAS, tpCR rate was 56.7% (17/30, 95% CI: 37.43%-74.53%), bpCR rate was 60% (18/30, 95% CI:40.60%-77.34%), ORR was 90.0% (27/30, 95% CI: 73.47%-97.89%). The incidence of TEAEs and CTCAE Grade ≥3 TEAEs were 100% (30/30) and 53.3% (16/30), respectively. The most common (≥5%）Grade ≥3 TEAEs were neutrophil count decreased (50%, 15/30), white blood cell count decreased (40.0%, 12/30), and lymphocyte count decreased (10%, 3/30). 7 (23.3%）pts required docetaxel dose reduction due to AEs. KN026 and docetaxel related SAEs occurred in only one patient. No Grade 5 TEAEs occurred.

Conclusions

KN026 plus docetaxel as neoadjuvant treatment has shown promising clinical benefit and acceptable safety for pts with HER2+ early or LABC. Further validation in a large-scale randomized controlled trial is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Alphamab Biopharmaceuticals Co. Ltd.

Funding

Jiangsu Alphamab Biopharmaceuticals Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.