Clinical Summary: 

• Design/Population: The phase 3 ARTEMIS-011 trial randomized patients aged 12 years and older with relapsed or refractory osteosarcoma who underwent at least 2 prior lines of systemic therapy to receive either risvutatug rezetecan, a B7-H3-directed antibody-drug conjugate, or gemcitabine plus docetaxel.
• Key Outcomes: Risvutatug rezetecan significantly prolonged progression-free survival compared with gemcitabine plus docetaxel, reducing the risk of disease progression or death by 67%. Overall survival data remained immature but showed a favorable numerical trend. Grade ≥3 treatment-emergent adverse events and treatment-related serious adverse events were more frequent with risvutatug rezetecan. 
• Clinical Relevance: These findings support risvutatug rezetecan as a potential new treatment option for heavily pretreated patients with relapsed or refractory osteosarcoma, demonstrating improved disease control compared with chemotherapy. Longer follow-up is required to confirm survival benefit and further characterize safety. 

Results from the phase 3 ARTEMIS-011 trial demonstrated that risvutatug rezetecan significantly improved progression-free survival (PFS) compared with gemcitabine plus docetaxel in heavily pretreated patients with relapsed or refractory osteosarcoma, supporting the B7-H3-directed antibody-drug conjugate as a potential new treatment option.

These findings were presented by Lu Xie, MD, Peking University People's Hospital, Beijing, China, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this multicenter, open-label trial, 122 patients aged 12 years or older with relapsed or refractory osteosarcoma who received at least 2 prior lines of systemic therapy were randomized 2:1 to receive either 12 mg/kg risvutatug rezetecan every 3 weeks (n = 80) or gemcitabine plus docetaxel every 3 weeks. (n = 42). 

 The primary end point was PFS, as assessed via blinded independent central review. Key secondary end points included investigator-assessed PFS, overall survival (OS), and safety. 

At a median follow-up of 7.1 months, median PFS was 5.5 months in the risvutatug rezetecan arm and 1.4 months in the gemcitabine plus docetaxel arm, reducing the risk of disease progression or death by 67% (hazard ratio [HR], 0.33; P < .0001).

Investigator-assessed PFS was consistent with the primary analysis, with a median of 5.6 months and 1 month, respectively. 

Although OS data remained immature, a numerical trend favoring risvutatug rezetecan was observed (HR, 0.51). 

Grade ≥3 treatment-emergent adverse events were reported in 92.5% of patients receiving risvutatug rezetecan and 83.3% receiving gemcitabine plus docetaxel. 

Treatment-related serious adverse events were reported in 63.8% of patients receiving risvutatug rezetecan and 28.6% receiving gemcitabine plus docetaxel, primarily driven by hematologic toxicities.

Treatment-related adverse events led to discontinuation in 3.8% of patients receiving risvutatug rezetecan and 2.4% receiving gemcitabine plus docetaxel. 

One case of grade 2 treatment-related interstitial lung disease was reported in the risvutatug rezetecan arm, which subsequently resolved. No treatment-related deaths or new safety signals were reported.

The investigators concluded that risvutatug rezetecan demonstrated a statistically significant and clinically meaningful improvement in PFS compared with gemcitabine plus docetaxel, accompanied by a favorable numerical OS trend and a manageable safety profile, supporting its potential as a new treatment standard for patients with relapsed or refractory osteosarcoma.

Source: 

Xie L, Yao W, Hua Y, et al. Risvutatug rezetecan (Ris-Rez) versus gemcitabine and docetaxel (GD) in heavily pretreated patients (pts) with relapsed or refractory (R/R) osteosarcoma: Primary results from the phase 3 ARTEMIS-011 study. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA9.