The designation was supported by preliminary data from the phase 1 ARTEMIS-001 trial (NCT05276609). Findings presented at the IASLC 2024 World Conference on Lung Cancer demonstrated that patients with extensive-stage SCLC (ES-SCLC) treated with the ADC at a dose of 8.0 mg/kg (n = 31) achieved an overall response rate (ORR) of 61.3% (95% CI, 42.2%-78.2%) and a disease control rate (DCR) of 80.6% (95% CI, 62.5%-92.5%).2 In patients treated at a dose of 10.0 mg/kg (n = 22), the ORR and DCR were 50.0% (95% CI, 28.2%-71.8%) and 95.5% (95% CI, 77.2%-99.9%), respectively.
Additionally, the median duration of response (DOR) was 6.4 months (95% CI, 4.2-12.7) in the 8.0-mg/kg cohort and 8.9 months (95% CI, 2.7-not applicable) in the 10.0-mg/kg cohort. The median progression-free survival (PFS) was 5.9 months (95% CI, 4.4-8.5) and 7.3 months (95% CI, 3.4-11.0), respectively.
Regarding safety across the 8.0-mg/kg and 10.0-mg/kg doses, the most common grade 3 or higher treatment-related adverse effects (TRAEs) reported in at least 10% of patients included decreased neutrophil count (39.3%), decreased white blood cell count (33.9%), decreased lymphocyte count (25.0%), decreased platelet count (17.9%), and anemia (16.1%).
How was the ARTEMIS-001 trial designed?
ARTEMIS-001 was an open-label, multicenter, dose-escalation and -expansion study that evaluated risvutatug rezetecan in patients at least 18 years of age with histologically or cytologically confirmed, locally advanced or metastatic solid tumors who did not have standard treatment options available, or who had progressed on or were intolerant to standard therapies.3 All patients were required to have at least 1 extra-cranial lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks.
Patients with ES-SCLC enrolled in the dose-expansion portion were required to have prior treatment with platinum-based chemotherapy with or without immunotherapy, although no more than 3 prior lines of therapy were permitted.2 Patients were unselected for B7-H3 expression, and those with treated and stable brain metastases were allowed to participate.
During dose escalation, risvutatug rezetecan was evaluated at doses of 1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg, 6.0 mg/kg, 8.0 mg/kg, 12.0 mg/kg, and 16.0 mg/kg. In dose expansion, investigators randomly assigned patients with ES-SCLC 1:1 to receive risvutatug rezetecan at 8.0 mg/kg or 10.0 mg/kg given once every 3 weeks.
ORR per RECIST 1.1 criteria served as the primary end point for the dose-expansion portion of the study. Secondary end points comprised safety, pharmacokinetics, DOR, DCR, PFS, and overall survival.
What additional data were reported for risvutatug rezetecan?
Notably, no correlation was reported between B7-H3 expression and tumor response. At the 8.0-mg/kg dose, the ORR was 75.0% (95% CI, 34.9%-96.8%) for patients with a B7-H3 expression of less than 1% (n = 8) and 61.9% (95% CI, 38.4%-81.9%) for those with an expression between 1% and 100% (n = 29). At the 10.0-mg/kg dose level, the ORRs were 71.4% (95% CI, 29.0%-96.3%) for those with an expression below 1% (n = 7) and 42.9% (95% CI, 17.7%-71.1%) for those with an expression of at least 1% (n = 14).
Further safety data showed that the most common any-grade TRAEs reported in at least 20% of patients across the 2 dose levels included anemia (85.7%), decreased white blood cell count (80.4%), decreased neutrophil count (67.9%), decreased platelet count (53.6%), nausea (51.8%), pyrexia (48.2%), decreased appetite (42.9%), increased alanine aminotransferase levels (39.3%), increased aspartate aminotransferase levels (39.3%), asthenia (39.3%), vomiting (39.3%), decreased lymphocyte count (32.1%), hypoalbuminemia (30.4%), decreased weight (23.2%), and hyponatremia (21.4%).
References
- GSK’227, a B7-H3-targeted antibody-drug conjugate, granted orphan drug designation in small-cell lung cancer by the US FDA. News release. GSK. December 10, 2025. Accessed December 11, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-227-a-b7-h3-targeted-antibody-drug-conjugate-granted-orphan-drug-designation-in-small-cell-lung-cancer-by-the-us-fda/
- Wang J, Duan J, Wu L, et al. Efficacy and safety of HS-20093 in extensive stage small cell lung cancer in a multicenter, phase 1 study (ARTEMIS-001). Presented at: 2024 IASLC World Conference on Lung Cancer; September 6-10, 2024; San Diego, CA. Abstract OA04.06.
- ARTEMIS-001: phase 1 study of the HS-20093 in patients with advanced solid tumors. ClinicalTrials.gov. Updated February 15, 2023. Accessed December 11, 2025. https://clinicaltrials.gov/study/NCT05276609
