Ris-Rez Improves PFS in Relapsed/Refractory Osteosarcoma

Risvutatug rezetecan (Ris-Rez) improved progression-free survival (PFS) by blinded independent central review (BICR) vs gemcitabine plus docetaxel in patients with relapsed/refractory osteosarcoma whose disease progressed after at least 2 prior lines of systemic therapy, according to primary results from the phase 3 ARTEMIS-011 trial (NCT06935409) presented at the 2026 ESMO Congress.¹

At a data cutoff of June 17, 2026, the median BICR-assessed PFS was 5.5 months (95% CI, 4.1-7.4) with Ris-Rez (n = 80) vs 1.4 months (95% CI, 0.8-2.7) with gemcitabine plus docetaxel (n = 42), translating to a 67% reduction in the risk of disease progression or death (HR, 0.33; 95% CI, 0.20-0.55; P < .0001). The 4-month PFS rates were 65% and 33%, respectively. The PFS benefit was consistent across predefined subgroups.

The BICR-assessed objective response rate (ORR) was 15% with Ris-Rez vs 2.4% with gemcitabine plus docetaxel (odds ratio [OR], 7.1; 95% CI, 0.9-56.1), and the disease control rate (DCR) was 76% vs 33% (OR, 6.2; 95% CI, 2.8-14.0). By BICR, the median duration of response (DOR) with Ris-Rez was 7.6 months; the median DOR was not reached in the control arm, where only 1 patient had a partial response.

"ARTEMIS-011 suggests that [Ris-Rez] is a promising new treatment option for patients with previously treated advanced relapsed/refractory osteosarcoma," presenting author Lu Xie, MD, of the Musculoskeletal Tumor Center at Peking University People's Hospital in Beijing, China, said in a presentation of the data.

How was the phase 3 ARTEMIS-011 trial of Ris-Rez in R/R osteosarcoma designed?

Ris-Rez is an antibody-drug conjugate designed to target B7-H3, and it carries a topoisomerase 1 inhibitor, with roughly 4 payload molecules attached to each antibody. The agent received FDA breakthrough therapy designation for late-line relapsed/refractory osteosarcoma in January 2025 based on data from the phase 2 ARTEMIS-002 trial (NCT04502044), and topline results announced in July 2026 showed that ARTEMIS-011 had met its primary end point.²

ARTEMIS-011 investigators enrolled patients 12 years of age or older in the open-label, randomized, multicenter study.¹ Eligible patients had osteosarcoma confirmed by pathology who had progressed on, or been unable to tolerate, at least 2 prior lines of systemic therapy. Patients needed to have 1 or more measurable target lesions per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

Patients were randomly assigned 2:1 to receive Ris-Rez at 12.0 mg/kg intravenously on day 1 of each 3-week cycle or gemcitabine at 1000 mg/m² on days 1 and 8 plus docetaxel at 75 mg/m² on day 8, every 3 weeks. Patients in the control arm could cross over to Ris-Rez after BICR-confirmed progression.

Along with the primary end point of BICR-assessed PFS, secondary end points included overall survival (OS), investigator-assessed PFS, ORR, DCR, DOR, and safety.

In total, 122 patients were randomly assigned and received at least 1 study treatment at 24 sites in China. The median age was 22.0 years (interquartile range [IQR], 17.5-33.0) in the Ris-Rez arm and 21.0 years (IQR, 17.0-37.0) in the control arm; 25% and 26% of patients, respectively, were adolescents. The median number of prior lines of systemic therapy was 2.5 (range, 2-6) and 3.0, (range, 2-5), respectively, and 69% and 79% of patients had received prior targeted therapy. The median follow-up was 7.1 months.

What additional efficacy data were reported for Ris-Rez from ARTEMIS-011?

Investigator-assessed findings were consistent with the BICR analysis, with the median investigator-assessed PFS being 5.6 months (95% CI, 4.2-7.4) with Ris-Rez vs 1.0 month (95% CI, 0.7-2.3) with gemcitabine plus docetaxel (HR, 0.30; 95% CI, 0.19-0.50).

OS data were immature, with 10 deaths reported in each arm, representing 13% of patients in the Ris-Rez arm and 24% of those in the control arm. The median OS was not reached in either arm (HR, 0.51; 95% CI, 0.21-1.23). After progression, 17 patients in the control arm crossed over to receive Ris-Rez.

What was the safety profile of Ris-Rez vs gemcitabine plus docetaxel in osteosarcoma?

The median treatment duration was 4.5 months with Ris-Rez vs 1.5 months with gemcitabine and 1.4 months with docetaxel. Every patient in both arms had at least 1 treatment-related adverse effect (TRAE); grade 3 or higher TRAEs occurred in 93% of patients in the Ris-Rez arm vs 83% of patients in the control arm. Serious TRAEs occurred in 64% vs 29% of patients, respectively. No fatal TRAEs were reported.

TRAEs led to dose reductions in 71% of patients in the experimental arm vs 26% in the control arm; permanent treatment discontinuation rates due to TRAEs were 4% (n = 3) vs 2% (n = 1). One patient in the Ris-Rez arm developed grade 2 interstitial lung disease considered related to treatment; no cases were reported in the control arm.

The most common grade 3 or higher TRAEs with Ris-Rez vs chemotherapy were decreased white blood cell count (80% vs 40%), decreased neutrophil count (79% vs 43%), decreased platelet count (71% vs 60%), and anemia (63% vs 29%). Any-grade pyrexia (41% vs 10%), vomiting (38% vs 7%), and infusion-related reactions (25% vs 2%) were more common with Ris-Rez. Xie noted that prophylactic steroids were recommended before the first Ris-Rez infusion to address pyrexia.

According to the July 2026 topline announcement, the ARTEMIS-011 data are intended to support a regulatory submission for Ris-Rez in China.²

Disclosures: Xie reported no personal disclosures related to this study.

References

1. Xie L, Yao W, Hua Y, et al. Risvutatug rezetecan versus gemcitabine and docetaxel in heavily pretreated patients with relapsed or refractory osteosarcoma: primary results from the phase 3 ARTEMIS-011 study. Paper presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA9
2. GSK's licensor Hansoh Pharma announces positive results from a second phase III trial for Ris-Rez in China. News release. GSK. July 28, 2026. Accessed October 26, 2026. https://www.gsk.com/en-gb/media/press-releases/gsk-s-licensor-hansoh-pharma-announces-positive-results-from-a-second-phase-iii-trial-for-ris-rez-in-china/