2. Academic Validation
  3. First-in-human study of DP303c, a HER2-targeted antibody-drug conjugate in patients with HER2 positive solid tumors

First-in-human study of DP303c, a HER2-targeted antibody-drug conjugate in patients with HER2 positive solid tumors

  • NPJ Precis Oncol. 2024 Sep 12;8(1):200. doi: 10.1038/s41698-024-00687-7.
Jian Zhang # 1,  Yiqun Du # 1,  Yanchun Meng 1,  Xiaojun Liu 1,  Yuxin Mu 1,  Yunpeng Liu 2,  Yehui Shi 3,  Jufeng Wang 4,  Aimin Zang 5,  Shanzhi Gu 6,  Tianshu Liu 7,  Huan Zhou 8,  Hongqian Guo 9,  Silong Xiang 10,  Xialu Zhang 10,  Suqiong Wu 10,  Huanhuan Qi 10,  Mengke Li 10,  Xichun Hu 11
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center, Shanghai, China.
  • 2 The First Hospital of China Medical University, Shenyang, China.
  • 3 Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 4 Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
  • 5 Affiliated Hospital of Hebei University, Baoding, China.
  • 6 Hunan Cancer Hospital, Changsha, China.
  • 7 Zhongshan Hospital Fudan University, Shanghai, China.
  • 8 The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
  • 9 Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, China.
  • 10 CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd, Shijiazhuang, China.
  • 11 Fudan University Shanghai Cancer Center, Shanghai, China. huxichun2017@163.com.
  • # Contributed equally.
PMID: 39266619 DOI: 10.1038/s41698-024-00687-7
Abstract

DP303c is a HER2-targeted ADC with a cleavable linker-MMAE payload. Previous in vitro studies demonstrated that DP303c showed similar or better antitumor activity than T-DM1 in xenograft models. This was a multicenter, dose escalation and dose expansion phase 1 study in China. Eligible patients were 18-75 years old with HER2-positive advanced solid tumors who were unable to benefit from standard therapy. DP303c was administered intravenously every 3 weeks, with accelerated titration at lower dose of 0.5 mg/kg and 3 + 3 design with dose levels of 1.0, 2.0, 3.0 or 4.0 mg/kg at dose escalation part, followed by the selected dose level at dose expansion part. The primary endpoints were safety and tolerability, as well as identification of recommended phase 2 dose. As of Feb 28, 2023, 94 patients were enrolled and received DP303c (dose escalation: n = 22; dose expansion: n = 72), of whom 68 patients had breast Cancer. One dose limiting toxicity (Grade 3 eye pain) was observed at 4.0 mg/kg dose, and the maximum tolerated dose was not reached. The most common treatment-related adverse events at grade 3 or higher were blurred vison (16.0%), dry eye (6.4%), and peripheral neuropathy (5.3%). No treatment-related death occurred. Overall, among 91 efficacy evaluable patients, 39 patients (42.9%) achieved an objective response. Disease control was observed in 62 patients (68.1%). In 66 efficacy evaluable patients with breast Cancer, 34 patients achieved an objective response (51.5%). Disease control was achieved in 51 patients (77.3%). Median PFS was 6.4 months. On a molar basis, DP303c Cmax at 3.0 mg/kg doses was 132-folder higher than that for free MMAE. DP303c demonstrated promising anti-tumor activity with acceptable safety in patients with pre-treated advanced HER2 positive solid tumors, especially in breast Cancer. Based on safety and efficacy results, 3.0 mg/kg Q3W was determined as recommended phase 2 dose for DP303c. (Trial registration: ClinicalTrials.gov Identifier: NCT04146610).

Figures
Products