Disitamab vedotin, a HER2‐directed antibody‐drug conjugate, in patients with HER2‐overexpression and HER2‐low advanced breast cancer: a phase I/Ib study

Author:

Wang Jiayu1,Liu Yunjiang2,Zhang Qingyuan3,Li Wei4,Feng Jifeng5,Wang Xiaojia6,Fang Jianmin7,Han Yiqun1,Xu Binghe1

Affiliation:

1. Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P. R. China

2. Breast Center The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei P. R. China

3. Department of Breast Medicine Harbin Medical University Cancer Hospital Harbin Heilongjiang P. R. China

4. Department of Medical Oncology The First Hospital of Jilin University Changchun Jilin P. R. China

5. Department of Medical Oncology Jiangsu Cancer Hospital Nanjing Jiangsu P. R. China

6. Department of Breast Medicine Zhejiang Cancer Hospital Hangzhou Zhejiang P. R. China

7. School of Life Science and Technology Tongji University Shanghai P. R. China

Abstract

AbstractBackgroundDisitamab vedotin (DV; RC48‐ADC) is an antibody‐drug conjugate comprising a human epidermal growth factor receptor 2 (HER2)‐directed antibody, linker and monomethyl auristatin E. Preclinical studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast, gastric, and ovarian cancers with different levels of HER2 expression. In this pooled analysis, we report the safety and efficacy of DV in patients with HER2‐overexpression and HER2‐low advanced breast cancer (ABC).MethodsIn the phase I dose‐escalation study (C001 CANCER), HER2‐overexpression ABC patients received DV at doses of 0.5‐2.5 mg/kg once every two weeks (Q2W) until unacceptable toxicity or progressive disease. The dose range, safety, and pharmacokinetics (PK) were determined. The phase Ib dose‐range and expansion study (C003 CANCER) enrolled two cohorts: HER2‐overexpression ABC patients receiving DV at doses of 1.5‐2.5 mg/kg Q2W, with the recommended phase 2 dose (RP2D) determined, and HER2‐low ABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2‐low ABC.ResultsTwenty‐four patients with HER2‐overexpression ABC in C001 CANCER, 46 patients with HER2‐overexpression ABC and 66 patients with HER2‐low ABC in C003 CANCER were enrolled. At 2.0 mg/kg RP2D Q2W, the confirmed objective response rates were 42.9% (9/21; 95% confidence interval [CI]: 21.8%‐66.0%) and 33.3% (22/66; 95% CI: 22.2%‐46.0%), with median progression‐free survival (PFS) of 5.7 months (95% CI: 5.3‐8.4 months) and 5.1 months (95% CI: 4.1‐6.6 months) for HER2‐overexpression and HER2‐low ABC, respectively. Common (≥5%) grade 3 or higher treatment‐emergent adverse events included neutrophil count decreased (17.6%), gamma‐glutamyl transferase increased (13.2%), asthenia (11.0%), white blood cell count decreased (9.6%), peripheral neuropathy such as hypoesthesia (5.9%) and neurotoxicity (0.7%), and pain (5.9%).ConclusionDV demonstrated promising efficacy in HER2‐overexpression and HER2‐low ABC, with a favorable safety profile at 2.0 mg/kg Q2W.

Publisher

Wiley

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