A TARGETED therapy significantly reduced the risk disease progression or death by more than double compared with chemotherapy in patients with hard-to-treat osteosarcoma, according to Phase III results presented at the European Society for Medical Oncology (ESMO) Congress 2026.
In the ARTEMIS-011 trial, testing antibody–drug conjugate risvutatug rezetecan in patients with heavily pretreated, relapsed or refractory osteosarcoma, saw a 67% reduction in the risk of progression or death (HR 0.33%).1
Median progression-free survival reached 5.5 months with risvutatug rezetecan, compared with 1.4 months with gemcitabine plus docetaxel, while the drug’s objective response rate was 15%.
The findings, presented in the Presidential Symposium at the ESMO congress, support risvutatug rezetecan as a potential treatment option after previous systemic therapy, despite that overall survival data remain immature.
Risvutatug rezetecan targets B7-H3 and carries a topoisomerase I inhibitor payload. The approach offers a new direction in osteosarcoma, the most common primary bone cancer in children and young people, with around 160 diagnoses annually in the UK according to the Bone Cancer Research Trust.
Current treatment for high-grade disease combines surgery with chemotherapy, often methotrexate, doxorubicin and cisplatin in suitable younger patients. Surgical removal remains important for resectable recurrence, but there is no standard second-line chemotherapy regimen.
To explore this new potential treatment, ARTEMIS-011 enrolled 122 patients in China aged 12 years or older whose disease had progressed or relapsed after at least two systemic treatment lines. Median age was 21 years, and 31 participants were adolescents.
Patients were randomly assigned 2:1 to risvutatug rezetecan 12 mg/kg every 3 weeks or gemcitabine plus docetaxel. Eighty patients were assigned to risvutatug rezetecan and 42 to chemotherapy.
The primary endpoint for the study was progression-free survival assessed by blinded independent central review.
At the data cut-off of 17 June 2026, median follow-up was 7.1 months and the progression-free survival benefit of the risvutatug rezetecan was statistically significant (HR: 0.33; 95% CI: 0.20–0.55; p<0.0001). Investigator-assessed median progression-free survival was consistent with the central review findings, at 5.6 versus 1.0 months.
Overall survival showed a favourable numerical trend (HR: 0.51; 95% CI: 0.21–1.23), but the confidence interval included no difference between groups. A survival benefit has therefore not been established.
Grade 3 or higher treatment-emergent adverse events occurred in 92.5% of patients receiving risvutatug rezetecan and 83.3% receiving chemotherapy. Serious treatment-related adverse events occurred in 63.8% and 28.6%, respectively, mainly driven by haematological toxicities.
Treatment-related adverse events led to discontinuation in 3.8% with the ADC and 2.4% with chemotherapy. One treatment-related case of grade 2 interstitial lung disease occurred with risvutatug rezetecan and resolved. No treatment-related deaths were reported.
While overall survival data are immature, Dr Nathalie Gaspar from the Gustave Roussy Cancer Campus Villejuif, France, said: “It is also promising that several partial responses were observed with this ADC as monotherapy, with a BICR-assessed overall response rate (ORR) of 15%.”
Although ARTEMIS-011 brings hope in the field which has seen little advancement in recent years, Gaspar cautions that “Osteosarcomas are very complex in terms of their genetics and tumour microenvironment, and we do not currently fully understand the biology underpinning the efficacy of risvutatug rezetecan.”
The investigators concluded that the progression-free survival improvement supports risvutatug rezetecan as a potential new treatment option for relapsed or refractory osteosarcoma. However, longer follow-up will be important to clarify overall survival and the treatment’s benefit–risk balance.
Reference
Xie L et al. Risvutatug rezetecan (Ris-Rez) versus gemcitabine and docetaxel (GD) in heavily pretreated patients with relapsed or refractory osteosarcoma: primary results from the phase 3 ARTEMIS-011 study. Abstract LBA9. NCT06935409. Abstract. ESMO Congress, 23-27 October 2026.
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