Lu Xie, MD of Peking University People's Hospital, China. 

Dr Xie on the ARTEMIS-002 Study Investigating HS-20093 in Relapsed/Refractory Sarcomas

“After we finished [analyzing] cohorts 1 and 2, we noticed that osteosarcoma might be a good population subtype for this drug. For osteosarcoma, many adolescent and young adult [patients] need to get enrolled into a phase 3 [trial]. For cohort 3, we [enrolled] 10 more adolescent patients to check the immunogenicity and pharmacokinetics for these patients.”

Lu Xie, MD, a medical oncologist at Peking University People’s Hospital, discussed the design and objectives of the phase 2 ARTEMIS-002 trial (NCT05830123), which is evaluating the B7-H3–targeted antibody-drug conjugate (ADC) HS-20093 in patients with relapsed or refractory sarcomas. The trial is an open-label, multicohort study and represents the first clinical evaluation of HS-20093 in this patient population. The study builds upon findings from the prior phase 1 dose-escalation ARTEMIS-001 trial (NCT05276609), in which objective responses were observed with the agent across several sarcoma subtypes, including osteosarcoma, at doses of 8 mg/kg and 12 mg/kg, with acceptable tolerability.

Xie explained that cohort 1 of ARTEMIS-002 enrolled patients with relapsed or refractory osteosarcoma. This cohort was designed to determine the optimal dosing strategy by directly comparing efficacy and tolerability between 2 dose levels: 8 mg/kg and 12 mg/kg of HS-20093. Based on early observations from ARTEMIS-001, clinical activity appeared more pronounced at the higher 12-mg/kg dose, although the safety profiles were comparable between the dose levels. To confirm these preliminary findings, the trial was subsequently expanded by an additional 10 patients to comprise cohort 3 and further assess the efficacy, duration of response, and dose-related toxicities associated with the ADC.

Cohort 2 included adult patients with other relapsed or refractory sarcoma subtypes, excluding osteosarcoma. This cohort evaluated HS-20093 at the recommended phase 2 dose (RP2D) of 12 mg/kg. Overall, the primary objectives of the trial were to assess objective response rate and safety in a broader sarcoma population and to validate the RP2D established in earlier clinical work.

Following the evaluation of cohorts 1 and 2, the study design was further refined to include cohort 3, which enrolled adolescent and young adult patients with osteosarcoma. Xie noted that this group was incorporated to explore the immunogenicity and pharmacokinetic profile of HS-20093 in younger patients, as osteosarcoma predominantly affects this age group.

Xie emphasized that the trial is structured to define the efficacy, safety, and optimal dosing of HS-20093 across both adult and adolescent populations. The study is expected to inform future late-phase development and support the advancement of B7-H3–directed ADC therapy as a potential treatment strategy for patients with relapsed or refractory sarcomas.

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Lu Xie, MD, discusses the design of the phase 2 ARTEMIS-002 trial.

Xie Sarcoma

“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.

Lu Xie, MD, discusses the scientific rationale and clinical development strategy for HS-20093 in the phase 2 ARTEMIS-002 trial.

Lu Xie, MD

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Dr Xie on the ARTEMIS-002 Study Investigating HS-20093 in Relapsed/Refractory Sarcomas

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