ARTEMIS-002: Phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma.
Authors: Lu Xie, Jie Xu, Xin Sun, Xin Liang, Kuisheng Liu, Yi Yang, Tao Ji, Guowen Wang, Jingnan Shen, Haiyan Hu, Yingqi Hua, Zhaoming Ye, Jianning Zhao, Weitao Yao, Jin Wang, Xianan Li, Meiyu Fang, Wei Guo, Xiaodong Tang
Journal: Journal of Clinical Oncology (2024)

11507 Background: Patients (pts) with relapsed and refractory (R/R) osteosarcoma have a poor prognosis with limited therapeutic options. HS-20093 is a novel antibody-drug conjugate (ADC) targeting B7-H3, which showed preliminary anti-tumor activity in phase 1 ARTEMIS-001 study (NCT05276609). Here we report results in R/R osteosarcoma pts treated with HS-20093 from ARTEMIS-002 study (NCT05830123). Methods: ARTEMIS-002 trial is an open label, two-arm phase 2 trial in pts with R/R osteosarcoma or other sarcomas progressed upon standard systemic treatment. Based on the results of the phase 1 trial that the maximum tolerated dose was 12 mg/kg once every 3 weeks (Q3W) intravenous infusion, the osteosarcoma pts in the phase 2 trial were randomized to receiving HS-20093 either at 8 mg/kg or 12 mg/kg Q3W at a ratio of 1:1. The primary endpoint was objective response rate (ORR) according to RECIST1.1. B7-H3 expression was retrospectively evaluated by IHC in osteosarcoma FFPE tissue. Results: A total of 34 pts with R/R osteosarcoma were enrolled from June to December in 2023, receiving HS-20093 at the dose of either 8.0 mg/kg (N = 15) or 12.0 mg/kg (N = 19). Median age was 21.5 years (range: 18~65). At baseline, most pts were evaluated with clinical stage IV disease (32/34, 94.1%) and pulmonary metastasis (28/34, 82.4%). Twenty-two pts (64.7%) had received ≥3 prior lines therapy. Twenty-six pts (76.5%) had received 4 types of standard chemotherapies consisting of platinum, anthracyclines, ifosfamide and methotrexate. Treatment emergent adverse event (TEAEs) occurred in 33 pts (97.1%). The common grade 3/4 TEAEs (≥5%) were: neutropenia, leukopenia, thrombocytopenia, lymphopenia and anemia. The incidences of discontinuations, dose withhold and dose reductions were 2.9%, 11.8% and 23.5%, respectively. There was no TEAE leading to death. As of cut-off date (25 December, 2023), the median follow-up time was 4.1 months (95% CI: 1.4~5.5) among 21 response-evaluable pts (11 treated with 8 mg/kg and 10 with 12.0 mg/kg). The ORR of 12.0 mg/kg HS-20093 was 20.0%. Two confirmed partial responses were observed in pts with 12.0 mg/kg and remained on response until last follow-up, of which the longest duration of response was 4.0 months. The disease control rate was 81.8% (9/11) and 100% (10/10) in pts with 8 mg/kg and 12.0 mg/kg. The median progression-free survival of all 21 pts was not mature. B7-H3 is highly expressed in osteosarcoma with median H-score 185 (0~260). No correlation was observed between tumor response and B7-H3 expression level. The PK exposure of HS-20093 ADC, total Ab and payload increased with dose, approximately proportional to dose, with a half-life of 4 to 6 days, and no or minor accumulation after multiple doses of Q3W. Conclusions: The data has demonstrated that HS-20093 exhibited promising antitumor activity with acceptable toxicity in pts of heavily-pretreated R/R osteosarcoma. The enrollment of ARTEMIS-002 is continuing. Clinical trial information: NCT05830123 .