Risvutatug rezetecan (ris-rez; HS-20093/GSK5764227) significantly improved overall survival (OS) versus topotecan in patients with
Median OS was 18.5 months with ris-rez (n = 230) versus 10.3 months with topotecan (n = 231), for a stratified HR of 0.46 (95% CI, 0.35 - 0.62; P < .0001) at a median follow-up of 12.2 months. OS events had occurred in 33.5% and 52.4% of patients, respectively, and investigators reported a consistent OS benefit across all predefined subgroups.
The median progression-free survival (PFS) by blinded independent central review (BICR) was 7.2 months with ris-rez versus 3.0 months with topotecan (HR, 0.33; 95% CI, 0.25 - 0.42), and the BICR-assessed objective response rate (ORR) was 58.3% (95% CI, 51.6 - 64.7) versus 12.6% (95% CI, 8.6 - 17.5).
The disease control rate (DCR) was 90.4% (95% CI, 85.9 - 93.9) versus 60.2% (95% CI, 53.5 - 66.5), and the median duration of response (DOR) was 6.9 months (95% CI, 5.6 - 8.2) versuss 5.6 months (95% CI, 3.0 - 8.3), respectively.
"Ris-Rez demonstrated a statistically significant and clinically meaningful overall survival benefit over topotecan in patients with SCLC that progressed after platinum-based therapy, with a favorable safety profile," lead study author Jie Wang, MD, PhD, professor at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, said in a news release issued by the IASLC.2 "These results suggest the potential of ris-rez to define a new standard of care in relapsed SCLC."
SCLC exhibits high expression of the immune checkpoint protein B7-H3, which is associated with reduced survival. Ris-rez comprises a human anti–B7-H3 IgG1 monoclonal antibody conjugated at cysteine residues to the topoisomerase I inhibitor payload rezetecan (HS-9265) via a cleavable linker, with a drug-to-antibody ratio of approximately 4.
In the phase 1 ARTEMIS-001 trial (NCT05276609), the agent produced a confirmed ORR of 52.3% and a median OS of 13.0 months in heavily pretreated patients with extensive-stage SCLC. The US Food and Drug Administration (FDA) granted ris-rez orphan drug designation for SCLC in December 2025,3 and the sponsor announced in July 2026 that ARTEMIS-008 had met its primary OS end point.4
ARTEMIS-008 was one of 2 phase 3 trials assessing B7-H3–directed ADCs versus topotecan in relapsed SCLC presented in the same WCLC plenary session. In
The multicenter, open-label study enrolled patients ≥18 years old with SCLC that relapsed after first-line platinum-based therapy and an ECOG performance status of 0 or 1. A total of 461 patients in China were randomly assigned 1:1 to intravenous ris-rez at 8.0 mg/kg every 3 weeks or topotecan at 1.2 mg/m2 on days 1 - 5 every 3 weeks, stratified by chemotherapy-free interval (<90 vs ≥90 days), baseline brain metastases, and disease stage at study entry. Treatment continued until disease progression or another discontinuation criterion was met.
The primary end point was OS; secondary end points included PFS, ORR, DCR, and DOR, plus safety. The interim OS analysis was preplanned at 192 events, representing 75% of the 256 events required for the final analysis.
Baseline characteristics were balanced. Median age was 61.5 years in the ris-rez arm and 63.0 years in the topotecan arm. All patients were Asian, 83.5% and 82.3% were male, and 80.9% and 84.8% had an ECOG performance status of 1. Extensive-stage disease at study entry was present in 87.0% and 87.9% of patients, 82.6% and 79.2% had received a prior PD-(L)1 inhibitor, 36.1% and 36.8% had a chemotherapy-free interval of less than 90 days, 19.1% and 19.9% had brain metastases, and 21.3% and 27.7% had liver metastases. Median duration of exposure was 6.9 months with ris-rez versus 2.8 months with topotecan.1
Investigator-assessed outcomes were consistent with BICR findings. Median PFS was 7.8 months with ris-rez versus 4.0 months with topotecan (HR, 0.35; 95% CI, 0.28 - 0.45). Complete responses by BICR occurred in 4 patients (1.7%) receiving ris-rez, with the remaining responses being partial; no complete responses were reported with topotecan.
Treatment-related adverse events (TRAEs) of any grade occurred in 100% of patients in both the ris-rez (n = 230) and topotecan (n = 216) arms. Grade ≥3 TRAEs occurred in 60.9% versus 78.2%, serious TRAEs in 34.3% versus 37.5%, TRAEs leading to dose delay in 38.3% versus 39.8%, TRAEs leading to dose interruption in 11.3% vs 0.5%, TRAEs leading to dose reduction in 20.4% versus 38.0%, and TRAEs leading to treatment discontinuation in 9.1% versus 4.2%.
Three patients (1.3%) in the ris-rez arm died of TRAEs — pneumonia, septic shock, and Pneumocystis jirovecii pneumonia in 1 patient each — versus 2 (0.9%) in the topotecan arm, from septic shock with respiratory failure and from myelosuppression.
The most common grade ≥3 TRAEs in both arms were hematologic, including decreased neutrophil, white blood cell, lymphocyte, and platelet counts and anemia.1,2
Interstitial lung disease (ILD) events occurred in 27 patients (11.7%) receiving ris-rez versuss 4 (1.9%) receiving topotecan; grade ≥3 events occurred in 3.9% versus 0.9%, and no grade 4 or 5 ILD events were reported.
Investigators concluded that ris-rez had a favorable safety profile with no new safety signals and that the data support the ongoing global phase 3 EMBOLD-SCLC-301 trial (NCT07099898) in patients with relapsed SCLC.
