TROP-2-targeted antibody-drug conjugate SHR-A1921 for advanced or metastatic solid tumors: A first-in-human phase 1
Jia Zhong1, Lin Wu2, Zhengbo Song3
1State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Abstract:
This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.
Insights
The antibody-drug conjugate SHR-A1921 shows promising antitumor activity in patients with advanced solid tumors. This TROP-2 targeted therapy demonstrated a manageable safety profile, with a dose of 3.0 mg/kg selected for further trials.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Trophoblast cell-surface antigen 2 (TROP-2) is a target for cancer therapy.
- Antibody-drug conjugates (ADCs) offer targeted delivery of cytotoxic agents.
Purpose of the Study:
- To evaluate the safety and efficacy of SHR-A1921, a novel TROP-2-targeted ADC.
- To determine the recommended dose for further clinical development.
Main Methods:
- Phase 1, three-stage, first-in-human trial (NCT05154604).
- 391 patients with pretreated advanced/metastatic solid tumors received SHR-A1921 (1.5-6.0 mg/kg every 3 weeks).
- Assessed treatment-related adverse events, objective response rate (ORR), and pharmacokinetics.
Main Results:
- Overall ORR was 24.8% (95% CI, 20.6-29.4) across various tumor types.
- Most common Grade ≥3 adverse event was stomatitis (14.6%).
- Low incidence of hematologic toxicities observed (3.1% Grade ≥3 neutropenia).
Conclusions:
- SHR-A1921 demonstrated promising antitumor activity and a manageable safety profile.
- A dose of 3.0 mg/kg every 3 weeks was selected for further clinical development.
- No significant correlation between TROP-2 expression and treatment efficacy was found.
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