The investigational antibody-drug conjugate (ADC) risvutatug rezetecan (Ris-Rez) significantly improved progression-free survival (PFS) in patients with relapsed or refractory osteosarcoma, the phase III ARTEMIS-011 trial from China showed.
Median PFS assessed by blinded independent central review (BICR) was 5.5 months for patients randomized to receive Ris-Rez compared with 1.4 months for those who received gemcitabine and docetaxel (HR 0.33, 95% CI 0.20-0.55, P<0.0001), reported Lu Xie, MD, of Peking University People's Hospital in Beijing, at the European Society for Medical Oncology annual congress in Madrid.
The PFS rate at 4 months was 65% with the B7-H3-targeted drug versus 33% with chemotherapy, with the PFS benefit demonstrated across subgroups.
Overall survival results were immature, but showed a trend in favor of Ris-Rez (HR 0.51, 95% CI 0.21-1.23).
These results suggest “Ris-Rez is a promising new treatment option for patients with previously treated, advanced, relapsed or refractory osteosarcoma,” Xie said.
While rare, osteosarcoma is the most common malignant bone tumor among children, adolescents, and young adults.
Treatment options are limited for recurrent or refractory osteosarcoma after first-line chemotherapy, with no clearly defined standard of care, and with survival rates that have not improved over the past several decades. Options are even more limited for patients who have progressed after second-line therapy, thus representing a substantial unmet medical need.
“Over time, the clinical trial landscape for osteosarcoma “has been quite disappointing,” said invited discussant Nathalie Gaspar, MD, PhD, of Gustave Roussy in Villejuif, France. “They are usually single-arm, very small population trials … and age inclusion criteria that have not met the epidemiology of the disease.”
“But, when you look at the ARTEMIS-011 study … we are talking about a large, randomized, joint adolescent/adult phase III trial, with a new drug, and with significant efficacy results,” she pointed out. “Which is something we have not seen for years.”
Gaspar noted that chemotherapy has been a standard first-line treatment for osteosarcoma since the 1970s, and that although multikinase inhibitors have been on the market for 15 years, “we still don’t know how to use them in the first line.”
The question is whether ADCs are “the new hope” for osteosarcoma, she said, and whether they can be moved forward — even into the first line — more quickly.
Ris-Rez received an FDA breakthrough therapy designation for late-line relapsed/refractory osteosarcoma in January 2025 based on data from the phase II ARTEMIS-002 trial. The ADC also significantly improved overall survival in patients with relapsed small cell lung cancer in a Chinese trial.
ARTEMIS-011 was conducted at 24 sites in China and included 122 patients randomized 2:1 to Ris-Rez or gemcitabine/docetaxel, with crossover to Ris-Rez permitted after progression.
Median age was 22 in the Ris-Rez group and 21 in the chemotherapy group; about 25% of patients in each arm were between the ages of 12 and 17. The majority of patients were male, and the time from diagnosis to randomization was a median of about 2 years.
Most patients had lung metastases, and patients in the Ris-Rez group had a median of 2.5 prior lines of systemic therapy compared with 3 lines in the chemotherapy arm.
Median treatment duration was 4.5 months with Ris-Rez and 1.5 months with chemotherapy.
BICR-assessed disease control rates were 76% with Ris-Rez and 33% with chemotherapy (OR 6.2, 95% CI 2.8-14.0), but there was no significant difference in BICR-assessed objective response rates (15% vs 2%, respectively; OR 7.1, 95% CI 0.9-56.1). The median duration of response was 7.6 months with Ris-Rez and not reached in the chemotherapy arm (with just one patient achieving a partial response).
Grade ≥3 treatment-related adverse events (TRAEs) were reported in 93% of patients in the Ris-Rez arm and 83% in the gemcitabine/docetaxel arm, while serious TRAEs were observed in 64% and 29%, respectively.
Most grade ≥3 TRAEs in both arms were hematologic, and one patient in the Ris-Rez arm had treatment-related interstitial lung disease (grade 2).
Dose reductions and delays or interruptions were more frequent in the Ris-Rez group, but there were few treatment discontinuations overall (4% in the Ris-Rez arm and 2% in the chemotherapy arm).
