HS-20093 demonstrated durable responses and disease control in relapsed/refractory osteosarcoma and STS in phase 2 ARTEMIS-002 trial data presented at ESMO 2025.
HS-20093, a novel B7-H3–directed antibody-drug conjugate (ADC), demonstrated encouraging antitumor activity and manageable safety in heavily pretreated patients with relapsed/refractory osteosarcoma and soft tissue sarcoma (STS), according to updated findings from the phase 2 ARTEMIS-002 trial (NCT05830123) that were presented at the
Among all patients with osteosarcoma who received HS-20093 at 12 mg/kg (n = 30), the confirmed objective response rate (ORR) was 20.0% (95% CI, 7.7%-38.6%) at a median follow-up of 16.0 months. 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]). The median progression-free survival (PFS) was 8.4 months (95% CI, 5.4-NE), and the 6-month PFS rate was 65.9% (95% CI, 44.1%-80.8%). The median overall survival (OS) was NE (95% CI, 15.4 months-NE), and the 15-month OS rate was 85.7% (95% CI, 61.5%-95.2%).
Among patients with other sarcomas including STS who received HS-20093 at 12 mg/kg (n = 20), the confirmed ORR was 25.0%. The DCR was 85.0% and the median DOR was 5.7 months.
In patients with STS only who received HS-20093 at 12 mg/kg (n = 13), the confirmed ORR was 23.1% (95% CI, 5.0%-53.8%) at a median follow-up of 19.0 months. The DCR and median DOR was 92.3% (95% CI, 64.0%-99.8%) and 12.5 months (95% CI, 5.5-NE), respectively. The median PFS and OS were 9.4 months (95% CI, 3.8-16.4) and 22.6 months (95% CI, 8.9-NE), respectively. The 6- and 15-month PFS and OS rates were 64.6% (95% CI, 30.6%-85.1%) and 68.4% (95% CI, 35.9%-86.8%), respectively.
“Compared with the 8.0-mg/kg every 3 weeks [Q3W] dose level, HS-20093 showed a better efficacy signal at 12.0 mg/kg Q3W in patients with relapsed/refractory osteosarcoma. HS-20093 at 12.0 mg/kg Q3W also showed a promising efficacy signal in patients with relapsed/refractory STS,” Lu Xie, MD, deputy medical director of the Musculoskeletal Tumor Center at Peking University People’s Hospital in Beijing, China, said.
A diagnosis of relapsed/refractory sarcoma portends a poor prognosis for which limited therapeutic options exist.
B7-H3 is overexpressed on the membranes of osteosarcoma cells relative to other co-stimulatory molecules within the B7 family. HS-20093 is a novel B7-H3–directed ADC built with a fully humanized anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase I inhibitor payload via a cleavable maleimide tetrapeptide.
In January 2025, the
The open-label, multicohort, phase 2 trial evaluated the efficacy and safety of HS-20093 in 3 cohorts: adult patients with osteosarcoma (cohort 1; n = 42); adult patients with other sarcomas [cohort 2; n = 20); and adolescent patients with osteosarcoma (cohort 3; n = 6).1
Eligible patients were at least 18 years old in cohorts 1 and 2 and between 12 and 17 years old in cohort 3. All patients must have received a diagnosis of histologically confirmed, relapsed/refractory osteosarcoma or other sarcoma that had progressed on at least 1 line of systemic therapy. Patients also had to have at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and agree to provide fresh or archival tumor tissue and peripheral blood samples.
In cohort 1, patients received either HS-20093 at 8.0 mg/kg Q3W (n = 16) or 12.0 mg/kg Q3W (n = 26). In cohort 2, patients with STS (n = 13) or other sarcomas excluding STS (n = 7) received HS-20093 at 12.0 mg/kg Q3W. In cohort 3, all patients received HS-20093 at 12.0 mg/kg Q3W.
The primary end points were investigator-assessed ORR in cohorts 1 and 2 and safety in cohort 3. Secondary end points included ORR by independent review committee, DCR, DOR, and PFS by investigator, OS, as well as safety, pharmacokinetics, and immunogenicity.
The data cutoff date was July 1, 2025, at which point 68 patients had been enrolled (osteosarcoma, n = 48; other sarcomas, n = 20). Xie noted that most patients had extensive metastases and were heavily pretreated with a median of 2 to 3 prior lines of therapy.
Baseline characteristics pooled from cohorts 1 and 3 indicated that patients with osteosarcoma who received HS-20093 at 12 mg/kg had a median age of 21 years (range, 12-55) and median BMI of 21.50 kg/m2 (range, 12.3-37.1). Most patients were male (n = 25; 78.1%) and had an ECOG performance status of 1 (n = 17; 53.1%). The median size of target lesions was 58.60 mm (range, 10.5-298.3); lesions were found in the lung (n = 28; 87.5%), bone (n = 20; 62.5%), pleura (n = 3; 9.4%), liver (n = 5; 15.6%), brain (n = 0; 0%), and other location (n = 6; 18.8%). Prior treatments included chemotherapy (n = 32; 100%), targeted therapy (n = 21; 65.6%), and immunotherapy (n = 16; 50%).
With respect to all patients in cohort 2, the median age was 35.5 years (range, 18-65) and median BMI was 23.35 kg/m2 (range, 14.1-29.4). Most patients were male (n = 12; 60%) and had an ECOG performance status of 1 (n = 13; 65%). The median size of target lesions was 71.40 mm (range, 21.4-222.0); lesions were found in the lung (n = 18; 90%), bone (n = 9; 45%), pleura (n = 2; 10%), liver (n = 2; 10%), brain (n = 1; 5%), and other location (n = 8; 40%). Most patients had received prior chemotherapy (n = 18; 90%), followed by targeted therapy (n = 16; 80%), and immunotherapy (n = 5; 25%).
Within cohort 1, responses were evaluated in the 8.0-mg/kg (n = 15) and 12.0-mg/kg (n = 24) arms. In the former, the confirmed ORR was 6.7% (95% CI, 0.2%-31.9%). The DCR and median DOR was 66.7% (95% CI, 38.4%-88.2%) and NE, respectively. The median PFS and OS was 4.0 months (95% CI, 1.2-11.0) and NE (95% CI, 9.4 months-NE), respectively. The 6- and 15-month PFS and OS rates were 33.3% (95% CI, 12.2%-56.4%) and 58.7% (95% CI, 30.0%-79.0%), respectively.
In the latter, the confirmed ORR was 20.8% (95% CI, 7.1%-42.2%). The DCR and median DOR was 87.5% (95% CI, 67.6%-97.3%) and 19.8 months (95% CI, 15.2-NE), respectively. The median PFS and OS was 8.4 months (95% CI, 2.8-NE) and NE (95% CI, 15.4-NE), respectively. The 6- and 15-month PFS and OS rates were 60.6% (95% CI, 35.6%-56.4%) and 84.7% (95% CI, 59.7%-94.8%), respectively.
In cohort 3, the confirmed ORR was 16.7% (95% CI, 0.4%-64.1%). The DCR and median DOR was 83.3% (95% CI, 35.9%-99.6%) and NE, respectively. The median PFS and OS was NE (95% CI, 1.4 months-NE) and NE, respectively. The 6- and 15-month PFS and OS rates were NE.
“HS-20093 at 12.0 mg/kg Q3W showed a manageable safety profile in patients with relapsed/refractory osteosarcoma and relapsed/refractory STS, and no new safety signal was identified,” Xie stated.
The overall incidence of adverse effects (AEs) was lower at 8.0 mg/kg than at 12 mg/kg. The most common grade 3 or greater treatment-related AEs (TRAEs) were hematologic in nature, largely reversible, and manageable with supportive care, according to Xie. The most common grade 3 or greater TRAEs in patients with osteosarcoma and STS, respectively, included decreased white blood cell count (37.5%; 84.6%), decreased neutrophil count (37.5%; 84.6%), and decreased lymphocyte count (37.5%; 61.5%).
The rate of TRAEs that were serious, required dose reduction, or dose discontinuation were 31.3%, 31.3%, and 4.2% in patients with osteosarcoma, respectively, and 69.2%, 61.5%, and 0% in patients with STS.
Treatment-related interstitial lung disease occurred in 2 patients with osteosarcoma (grade 1) and 1 patient with Ewing sarcoma (grade 2). Two treatment-emergent fatalities occurred, 1 of which was reported in a patient with chondrosarcoma and was deemed possibly related to study therapy.
“A confirmatory phase 3 study is evaluating HS-20093 12.0 mg/kg Q3W for efficacy and safety in Chinese patients with relapsed/refractory osteosarcoma. Outside of China, HS-20093 is under early clinical development in relapsed/refractory osteosarcoma and relapsed/refractory STS,” Xie concluded.
Disclosures: Xie had no personal disclosures related to the trial.
