Clinical Summary: 

• Design/Population: The phase 3 ARTEMIS-008 trial compared risvutatug rezetecan, a B7-H3–directed antibody-drug conjugate, with topotecan in patients with small cell lung cancer (SCLC) that experienced disease progression on or after platinum-based chemotherapy. 
• Key Outcomes: Risvutatug rezetecan significantly improved overall survival, reducing the risk of death by 54% compared with topotecan. The agent also improved progression-free survival and response, with an overall survival benefit observed across relevant patient subgroups. 
• Clinical Relevance: Risvutatug rezetecan provided broad efficacy with a more favorable safety profile, supporting its potential to become a new treatment options for patients with relapsed SCLC following platinum-based therapy. 

Results from the phase 3 ARTEMIS-008 trial demonstrated that risvutatug rezetecan significantly improved overall survival (OS) compared with topotecan in patients with small cell lung cancer (SCLC), who experienced disease progression on or after treatment with platinum-based chemotherapy. 

These results were presented in a plenary session at the World Conference on Lung Cancer by Jie Wang, MD, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 

In this open-label trial, 461 patients were randomized 1:1 to receive either 8 mg/kg of risvutatug rezetecan once every 3 weeks (n = 230) or 1.2 mg/m² topotecan on days 1 through 5 of each 3-week cycle (n = 231). Overall, 80.9% of patients had previously received treatment with a PD-L1 inhibitor.

Patients were stratified according to chemotherapy-free interval, presence of brain metastases, and disease stage at trial enrollment. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate, and safety.

At a median follow-up of 12.2 months, median OS was 18.5 months with risvutatug rezetecan arm and 10.3 months in the topotecan arm, corresponding to a 54% reduction in the risk of death (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.35 to 0.62; P < .0001). The OS benefit was consistent across all relevant subgroups.

By blinded independent central review, median PFS was 7.2 months in the risvutatug rezetecan arm and 3 months in the topotecan arm, corresponding to a 67% reduction in the risk of disease progression or death (HR, 0.33; 95% CI, 0.25 to 0.42). 

ORR was 58.3% in the risvutatug rezetecan arm and 12.6% in the topotecan arm, while the disease control rate was 90.4% and 60.2%, respectively. Investigator-assessed efficacy outcomes were consistent with those observed by blinded independent central review.

Grade ≥3 treatment-related adverse events occurred in 60.9% of patients receiving risvutatug rezetecan and 78.2% of patients receiving topotecan. The most common grade ≥3 events were hematologic in nature and included decreased neutrophil count (27% vs 40.7%), decreased white blood cell count (24.3% vs 32.4%), anemia (17.4% vs 25%), decreased lymphocyte count (16.1% vs 10.2%), and decreased platelet count (13.9% vs 59.7%).

ARTEMIS-008 demonstrated statistically significant and clinically meaningful improvements in OS, PFS, and response outcomes with risvutatug rezetecan compared with topotecan in relapsed SCLC. The magnitude of survival benefit, together with fewer high-grade treatment-related adverse events, supports risvutatug rezetecan as a potential new standard of care following platinum-based therapy.

Source: 

Wang J, Wang L, Duan J, et al. Risvutatug rezetecan (a B7-H3-Directed ADC) versus topotecan in relapsed SCLC: Primary results of phase 3 ARTEMIS-008. Presented at the World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract PL02.04