Findings from ARTEMIS-002 were presented during the 2025 ESMO Congress. Among both adult and pediatric patients with relapsed/refractory osteosarcoma treated at the 12.0-mg/kg level (n = 30), the confirmed overall response rate (cORR) was 20.0% (95% CI, 7.7%-38.6%), the disease control rate (DCR) was 86.7% (95% CI, 69.3%-96.2%), and the median duration of response (DOR) was 19.8 months (95% CI, 15.2-not evaluable [NE]). In patients with soft tissue sarcoma (n = 13), the cORR, DCR, and median DOR with the 12.0-mg/kg dose were 23.1% (95% CI, 5.0%-53.8%), 92.3% (95% CI, 64.0%-99.8%), and 12.5 months (95% CI, 5.5-NE), respectively. No new safety signals were identified.
“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, a medical oncologist at Peking University People’s Hospital in China, said in an interview with OncLive®.
Notably, HS-20093 was granted FDA breakthrough therapy designation for patients with relapsed/refractory osteosarcoma who have also progressed on 2 or more prior lines of therapy in January, 2025.2 The agent is being evaluated in both Chinese patients with relapsed/ refractory osteosarcoma and relapsed/refractory osteosarcoma or soft tissue sarcoma globally.
In the interview, Xie discussed the mechanistic rationale for developing HS-20093 in sarcoma, expanded on key efficacy and safety data with this agent from ARTEMIS-002, and noted the possibility of combining this drug with other agents to overcome secondary resistance.
OncLive: Why was B7-H3 chosen as a target for ADC development in sarcoma? What prior research supports this investigation?
Xie: In osteosarcoma, 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. [We don’t quite understand] the mechanism and the signature pathway, but it is a very optimal target for us to conjugate a drug to it.
During the phase 1a dose escalation trial, we noticed objective responses [with HS-20093] in osteosarcoma and other sarcomas at relatively low and high doses, and we think these are very promising. Therefore, we [initiated] this phase 2 trial to investigate the efficacy and appropriate dosage [of HS-20093] for these patients with sarcoma.
What was the design of the ARTEMIS-002 trial, and in which sarcoma subtypes was this agent evaluated?
This was an open-label, multi-cohort, phase 2 trial. In cohort 1, we wanted to explore the appropriate dosage for [HS-20093 in] osteosarcoma. During our dose escalation trial, we noticed responses at 8 mg/kg, and some patients responded at 12 mg/kg with tolerable toxicity.
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. For this adult cohort, we added 10 more patients to check the efficacy and the toxicity.
For Cohort 2, except for osteosarcoma, we investigated the recommended phase 2 dose of 12 mg/kg for other sarcomas in these adult cohorts. After we completed cohort 1 and 2, we noticed that osteosarcoma might be a very good population subtype for this drug. For osteosarcoma, many adolescents and young adults need to get into phase 3. For cohort 3, we also explored 10 more adolescent patients to check the immunogenicity and pharmacokinetics [of HS-20093].
At which dose level did HS-20093 show greater activity?
The primary end point for this study was ORR, but we all know that for osteosarcoma and other sarcomas, sometimes tumor shrinkage might not be so commonly seen. The most promising part of these results is that after several lines of TKI use—maybe the 3rd or 4th line of systemic treatment—we achieved a median PFS of 8.4 months for osteosarcoma and 9.4 months [95% CI, 3.8-16.4] for soft tissue sarcoma.1 This is long compared with [the median PFS achieved with] multi-targeted TKIs.
What is known so far about this agent’s safety profile? How does it compare/contrast with that of other standard regimens in the sarcoma?
The major toxicity [seen with] this drug was myelosuppression and cytopenias. However, comparing this [agent with] first-line or second-line chemotherapy in sarcoma, these adverse effects are manageable and tolerable. Additionally, 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.
What next steps are planned for the development of HS-20093?
Most sarcoma 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.
I also want to explore more biomarkers and the mechanism of drug resistance.
References
- Xiu L, Shen J, Xu J, et al. ARTEMIS-002: a phase 2 study of HS-20093 in patients with relapsed or refractory sarcomas. Ann Oncol.2025; 36 (suppl_2): S1447-S1478. doi:10.1016/annonc/annonc1938
- GSK’s B7-H3-targeted antibody-drug conjugate, GSK’227, receives US FDA breakthrough therapy designation in late-line relapsed or refractory osteosarcoma. News release. GSK. January 7, 2025. Accessed November 14, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-b7-h3-targeted-antibody-drug-conjugate-gsk227-receives-us-fda-breakthrough-therapy-designation-in-late-line-relapsed-or-refractory-osteosarcoma/
