Longer-term follow-up of the phase II ARTEMIS-002 trial continues to show promising efficacy of risvutatug rezetecan (ris-rez) in relapsed or refractory (R/R) sarcoma, with median overall survival (OS) reaching about 2 years, according to data presented at ESMO TAT Asia 2026.
The open-label study, conducted at multiple centres in mainland China, investigated the efficacy, safety, pharmacokinetics (PK) and immunogenicity of ris-rez – an investigational antibody-drug conjugate comprising a fully human anti–B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor payload – in patients with R/R sarcoma. [Xie L, et al, ESMO TAT Asia 2026]
The trial comprised three cohorts. Cohort 1 included 42 adults with osteosarcoma who were randomized to receive ris-rez 8 mg/kg Q3W (n=16) or 12 mg/kg Q3W (n=26). Cohort 2 included 20 adults with other sarcomas (soft-tissue sarcoma [STS], n=13; other sarcomas except STS, n=7) who received ris-rez 12 mg/kg Q3W. Cohort 3 included six adolescents (age, 12–17 years) with osteosarcoma who received ris-rez 12 mg/kg Q3W. Primary endpoints were objective response rate (ORR) by investigator assessment in cohorts 1 and 2, and safety in cohort 3.
“Most patients had extensive metastasis at baseline and were heavily pretreated with 2–3 lines of prior therapy,” said Dr Lu Xie of Peking University People’s Hospital, Beijing, China. “Sixty-six percent of patients with osteosarcoma and 80 percent of patients with other sarcomas had received tyrosine kinase inhibitors previously.”
Promising efficacy
“With longer follow-up [data cut-off, 20 September 2025], median OS was 24.5 months for ris-rez 8 mg/kg Q3W in osteosarcoma [n=15],” reported Xie.
Median OS was not reached (NR) for the 12 mg/kg dose in osteosarcoma (n=30), and 22.6 months for the 12 mg/kg dose in other sarcomas (n=20).
“All other efficacy results remained consistent with data reported at the ESMO 2025 Congress,” said Xie.
ORR was 6.7 and 20 percent for the 8 mg/kg and 12 mg/kg doses in osteosarcoma, respectively, and 23.1 percent for the 12 mg/kg dose in other sarcomas. Median progression-free survival was 4, 8.3 and 9.4 months, respectively.
Updated safety findings
“With longer follow-up, safety profile remained consistent with previous findings,” said Xie. “The most common grade ≥3 treatment-related adverse events [TRAEs] were haematological toxicities, which were largely reversible and manageable with standard supportive care.”
“The incidence of treatment-related serious AEs, TRAEs leading to dose reductions and TRAEs leading to dose discontinuation was 31.3, 31.3 and 4.2 percent in osteosarcoma, and 69.2, 61.5 and 0 percent in STS, respectively,” she continued.
Treatment-related interstitial lung disease events were observed in two patients with osteosarcoma (grade 1) and one patient with Ewing sarcoma (grade 2).
Two grade 5 treatment-emergent AEs were reported, one of which occurred in a patient with chondrosarcoma and was assessed by the investigator as possibly related to study drug.
PK & biomarker analysis
“Single-dose PK analysis showed that ris-rez exposure increased approximately dose-proportionally. No accumulation was observed after multiple doses,” reported Xie.
“Translational data showed no significant association between baseline B7-H3 expression and treatment outcomes in osteosarcoma, but the analysis was limited by small sample size,” she added.
A confirmatory phase III study is evaluating the efficacy and safety of ris-rez 12 mg/kg Q3W in Chinese patients with R/R osteosarcoma. [NCT06935409]