B7-H3-Targeted ADC HS-20093 Demonstrates Promising Efficacy in Relapsed/Refractory Sarcomas, Receives FDA Breakthrough Designation
核心洞察
The B7-H3 (搜索)-targeted antibody-drug conjugate HS-20093 achieved a 20% confirmed overall response rate in osteosarcoma (搜索) patients and 23.1% in soft tissue sarcoma (搜索) patients at the 12 mg/kg dose level in the phase 2 ARTEMIS-002 trial.
HS-20093 demonstrated superior efficacy at the higher 12 mg/kg dose compared to 8 mg/kg, with median progression-free survival of 8.4 months for osteosarcoma (搜索) and 9.4 months for soft tissue sarcoma (搜索).
The FDA granted breakthrough therapy designation to HS-20093 for relapsed/refractory osteosarcoma (搜索) patients who have progressed on two or more prior therapies in January 2025.
The B7-H3 (搜索)-targeted antibody-drug conjugate HS-20093 has demonstrated significant clinical activity in patients with relapsed or refractory sarcomas, with the phase 2 ARTEMIS-002 trial showing superior efficacy at higher dosing levels and supporting its advancement to phase 3 development. The findings were presented at the 2025 ESMO Congress by Lu Xie, MD, a medical oncologist at Peking University People's Hospital.
Strong Response Rates Across Sarcoma Subtypes
In the multicohort ARTEMIS-002 trial, HS-20093 at the 12.0-mg/kg dose level achieved a confirmed overall response rate (cORR) of 20.0% (95% CI, 7.7%-38.6%) among 30 adult and pediatric patients with relapsed/refractory osteosarcoma (搜索). The disease control rate reached 86.7% (95% CI, 69.3%-96.2%), with a median duration of response of 19.8 months (95% CI, 15.2-not evaluable).
For patients with soft tissue sarcoma (搜索) (n = 13), the 12.0-mg/kg dose produced a cORR of 23.1% (95% CI, 5.0%-53.8%), a disease control rate of 92.3% (95% CI, 64.0%-99.8%), and a median duration of response of 12.5 months (95% CI, 5.5-not evaluable).
Dose-Dependent Efficacy Establishes Optimal Treatment Level
The trial's design directly compared efficacy between 8 mg/kg and 12 mg/kg dose levels in cohort 1, which enrolled patients with relapsed or refractory osteosarcoma (搜索). "We first randomly assigned [patients to] cohort 1 into 2 cohorts to see the efficacy and the duration of response for these patients. We then noticed that the 12-mg/kg dose might [produce] better clinical outcomes compared with the 8-mg/kg dose," Xie explained.
The superior performance at the higher dose led to expansion of the study with an additional 10 patients to further validate the efficacy and toxicity profile. At the 12-mg/kg dose, HS-20093 produced a median progression-free survival of 8.4 months for adult and pediatric patients with osteosarcoma (搜索) and 9.4 months (95% CI, 3.8-16.4) for those with soft tissue sarcoma (搜索).
FDA Recognition and Regulatory Milestone
The clinical promise of HS-20093 gained regulatory recognition when the FDA granted breakthrough therapy designation for patients with relapsed/refractory osteosarcoma (搜索) who have progressed on two or more prior lines of therapy in January 2025. This designation acknowledges the drug's potential to address a significant unmet medical need in this challenging patient population.
Mechanistic Rationale and Target Selection
The development of HS-20093 was based on multiomic analysis identifying B7-H3 (搜索) as overexpressed on the membrane of osteosarcomas. "In osteosarcoma (搜索), we are exploring membrane molecules expressed on the surface of [the tumor]. [In a prior] multiomic analysis of these membrane molecules, we noticed that B7-H3 is overexpressed on the membrane of osteosarcomas," Xie noted.
The phase 2 ARTEMIS-002 trial built upon promising findings from the prior phase 1 dose-escalation ARTEMIS-001 trial, where objective responses were observed across several sarcoma (搜索) subtypes at both 8 mg/kg and 12 mg/kg doses with acceptable tolerability.
Manageable Safety Profile Supports Continued Development
The safety profile of HS-20093 proved manageable across the study population. "The major toxicity [seen with] this drug was myelosuppression and cytopenias. However, comparing this [agent with] first-line or second-line chemotherapy in sarcoma (搜索), these adverse effects are manageable and tolerable," Xie reported.
Notably, younger patients showed particular tolerance to the treatment. "In these young adults and adolescent patients, we noticed that the rate of interstitial lung disease/pneumonitis seems to be relatively low compared with older patients, because they have better pulmonary function and no other basic lung disease," Xie observed.
Comprehensive Study Design Addresses Multiple Patient Populations
The ARTEMIS-002 trial employed a sophisticated three-cohort design to comprehensively evaluate HS-20093 across different patient populations. Cohort 1 focused on dose optimization in osteosarcoma (搜索) patients, cohort 2 evaluated the recommended phase 2 dose of 12 mg/kg in adult patients with other sarcoma (搜索) subtypes excluding osteosarcoma, and cohort 3 specifically enrolled adolescent and young adult patients with osteosarcoma to assess immunogenicity and pharmacokinetic profiles.
"After we finished [analyzing] cohorts 1 and 2, we noticed that osteosarcoma (搜索) might be a good population subtype for this drug. For osteosarcoma, many adolescent and young adult [patients] need to get enrolled into a phase 3 [trial]. For cohort 3, we [enrolled] 10 more adolescent patients to check the immunogenicity and pharmacokinetics for these patients," Xie explained.
Future Development and Combination Strategies
The positive results from ARTEMIS-002 support advancement to confirmatory phase 3 studies, with ongoing evaluation planned among Chinese patients with relapsed/refractory osteosarcoma (搜索). However, Xie identified potential challenges that may require innovative approaches.
"Most sarcoma (搜索) patients may benefit from this drug. My concern for the future is [potential] secondary resistance, because when it happened, it happened so quickly and many more lesions come out. Moving forward, our next step might be [to evaluate HS-20093] in combination with other drugs so as to overcome this resistance and benefit more patients," Xie noted.
The research team also plans to explore biomarkers and mechanisms of drug resistance to optimize patient selection and treatment strategies. "It is worthwhile for us to explore [this agent in] more patients, to validate our assumption that this is a very useful drug for these patients," Xie concluded.