Ris-rez improved PFS vs chemotherapy in the ARTEMIS-011 trial for relapsed/refractory osteosarcoma.
The B7-H3-targeted antibody-drug conjugate risvutatug rezetecan (Ris-Rez; HS-20093) significantly improved of progression-free survival (PFS) vs chemotherapy in patients with osteosarcoma who progressed or relapsed after at least 2 prior lines of systemic therapy, meeting the primary end point of the phase 3 ARTEMIS-011 trial (NCT06935409).1
In addition to a statistically significant and clinically meaningful PFS improvement vs chemotherapy, Ris-Rez also displayed consistent benefits in regard to secondary end points such as overall survival (OS).
The safety profile for Ris-Rez was consistent with prior findings in this tumor type, and no new safety signals were identified.
"Building on recent pivotal data in small cell lung cancer [SCLC], these results strengthen our confidence in the broad potential of Ris-Rez and validate B7-H3 as a promising target across multiple tumour types," Hesham Abdullah, MD, MSc, senior vice president and global head of Oncology, Research and Development at GSK, stated in a news release.
Data from ARTEMIS-011 will be utilized for a regulatory submission in China.
Ris-Rez previously received
The randomized, open-label trial enrolled patients at least 12 years of age with at least 1 target lesion per RECIST 1.1 criteria.4 Patients also needed to have an ECOG performance status of 1 or less and a life expectancy higher than 12 weeks.
If patients had received B7-H3–targeting topoisomerase I inhibitors, had received systemic antitumor therapy with gemcitabine in combination with docetaxel, had residual toxicities that were higher than grade 2, had a history of other primary solid tumors, or had inadequate bone marrow reserve or liver and kidney organ function, they were not included in the trial.
Patients in the experimental arm received 12 mg/kg intravenous (IV) infusions of Ris-Rez continuously every 3 weeks until progression. Patients in the chemotherapy arm received 1000 mg/m2 of IV gemcitabine on days 1 and 8 alongside 75 mg/m2 of IV docetaxel on day 8 for each 21-day cycle.
Independent review committee-assessed PFS per RECIST 1.1 criteria was the primary end point of the trial, whereas OS, overall response rate (ORR), disease control rate (DCR) and duration of response served as secondary end points.
Data from ARTEMIS-002 showed that at a median follow-up of 3.3 months, patients who received Ris-Rez (n = 38) achieved an ORR of 10.5% (95% CI, 2.9%-21.1%), as well as a DCR of 78.9% (95% CI, 62.7%-90.4%).5 Moreover, those who received a 12 mg/kg dose in the trial (n = 23), similar to the dose of Ris-Rez in ARTEMIS-011, achieved respective ORRs and DCRs of 17.4% (95% CI, 5.0%-38.8%) and 87.0% (95% CI, 66.4%-97.2%).
In SCLC, Ris-Rez yielded statistically significant and clinically meaningful improvements in OS vs topotecan.3
The phase 1b/2 EMBOLD Sarcoma-202 trial (NCT07602777) evaluating the agent in previously treated unresectable advanced or metastatic sarcomas, including osteosarcoma, is currently enrolling patients.1 Ris-Rez is currently being developed in additional solid tumors, including lung and prostate cancers.
