Dr Xie on the Rationale for Investigating HS-20093 in Relapsed/Refractory Sarcomas

“During the phase 1a dose-escalation trial, we noticed objective responses [in patients with] osteosarcoma and other sarcomas at [both] relatively low doses and high doses, which is promising. [Therefore], we [initiated] this phase 2 trial to investigate the efficacy and appropriate dosage for these patients with sarcoma.”

Lu Xie, MD, a medical oncologist at Peking University People’s Hospital, discussed the scientific rationale and clinical development strategy for the phase 2 ARTEMIS-002 trial (NCT05830123), which is evaluating HS-20093, a B7-H3–targeted antibody-drug conjugate (ADC), in patients with relapsed or refractory sarcomas.

The study builds on early evidence of activity observed in the phase 1 ARTEMIS-001 (NCT05276609) dose-escalation trial, in which HS-20093 generated preliminary antitumor responses at both low and high doses across several sarcoma subtypes, including osteosarcoma. Xie explained that osteosarcoma remains one of the most treatment-refractory solid tumors, with limited options available after progression on standard chemotherapy. Through multi-omic profiling of osteosarcoma cell membranes, investigators led by Richard Gorlick, MD, at The University of Texas MD Anderson Cancer Center, identified B7-H3 as a highly expressed cell-surface molecule in osteosarcoma and other sarcomas, according to Xie. Although the complete signaling mechanisms and biological pathways associated with B7-H3 overexpression remain under investigation, its limited expression in normal tissues and broad prevalence across solid tumors make it an attractive therapeutic target, she said.

In the ARTEMIS-001 study, dose escalation of the ADC established a manageable safety profile, and early evidence of objective responses was observed even at lower dose levels, prompting its further investigation in the phase 2 setting, Xie noted. The ARTEMIS-002 trial aims to refine the dosing strategy and evaluate the efficacy of HS-20093 in a larger cohort of patients with relapsed or refractory sarcomas, including osteosarcoma. Key end points include objective response rate, duration of response, progression-free survival, and safety.