B7-H3 ADC Ris-Rez Cuts Death Risk 54% in Relapsed Small-Cell Lung Cancer
核心洞察
The Phase III ARTEMIS-008 trial showed risvutatug rezetecan (搜索) reduced the risk of death by 54% versus topotecan in relapsed small-cell lung cancer.
Median overall survival reached 18.5 months with Ris-Rez versus 10.3 months with topotecan after a median follow-up of 12.2 months.
Grade 3 or higher treatment-related adverse events occurred in 60.9% of Ris-Rez patients versus 78.2% with topotecan, mostly hematologic toxicities.
The B7-H3 (搜索)-directed antibody-drug conjugate (ADC) risvutatug rezetecan (搜索) (Ris-Rez) reduced the risk of death by 54% compared with topotecan in patients with relapsed small-cell lung cancer (SCLC) whose disease progressed on or after platinum-based chemotherapy, according to results from the randomized Phase III ARTEMIS-008 trial presented in a Presidential Symposium session at the 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea.
The data, announced by licensor Hansoh Pharmaceutical Group Co., Ltd. and being developed outside China by GSK, represent the first Phase III results to demonstrate an overall survival (OS) benefit for a B7-H3 (搜索) ADC in any tumor type.
Overall Survival and Secondary Endpoints
ARTEMIS-008 (NCT06498479) is a multicenter, open-label, randomized, active-controlled Phase III study conducted in China. A total of 461 patients with limited- or extensive-stage SCLC whose disease progressed on or after first-line platinum-based therapy were randomized 1:1 to receive Ris-Rez 8.0 mg/kg every three weeks or topotecan 1.2 mg/m² on days 1 through 5 of each 21-day cycle. More than 80% of patients had previously received PD-(L)1 inhibitors.
At the June 6, 2026 data cutoff, after a median follow-up of 12.2 months, median OS was 18.5 months with Ris-Rez (n=230) versus 10.3 months with topotecan (n=231), corresponding to a hazard ratio of 0.46 (95% CI, 0.35–0.62; P<0.0001). The OS benefit was consistent across relevant subgroups.
Blinded independent central review favored Ris-Rez across key secondary efficacy measures. Median progression-free survival was 7.2 months versus 3.0 months (HR 0.33; 95% CI, 0.25–0.42). The objective response rate was 58.3% versus 12.6%, and the disease control rate was 90.4% versus 60.2%. Investigator-assessed outcomes were consistent with the central review findings.
Safety Profile
Grade 3 or higher treatment-related adverse events (TRAEs) occurred less frequently with Ris-Rez than with topotecan, at 60.9% versus 78.2%. The most common grade 3 or higher TRAEs with Ris-Rez were hematologic toxicities, including decreased neutrophil count, decreased white blood cell count, anemia, decreased lymphocyte count and decreased platelet count. These hematologic TRAEs are considered manageable and consistent with the known side effects of this class of medicines.
Investigator and Sponsor Perspectives
Jie Wang, M.D., Chair of the Medical Oncology Department at the National Cancer Center, Chinese Academy of Medical Sciences, and Principal Investigator of the ARTEMIS-008 trial, framed the results against the current treatment landscape. "Relapsed small cell lung cancer (搜索) remains one of the most challenging cancers to treat, with few therapies delivering meaningful improvements in survival once the disease returns," Wang said. "In ARTEMIS-008, patients receiving Ris-Rez lived substantially longer while experiencing lower rates of severe treatment-related side effects. These findings suggest Ris-Rez could represent an important advance for patients."
Hesham Abdullah, Senior Vice President, Global Head of Oncology, R&D at GSK, said the data add to the growing body of evidence for Ris-Rez and mark an important step forward for the company's lung cancer portfolio. "The significant improvement in survival observed in this study, together with an encouraging safety profile, provide further momentum for GSK's global development of Ris-Rez across later-line and earlier treatment settings for small cell lung cancer (搜索)," Abdullah said.
Development Program and Regulatory Designations
GSK holds exclusive rights to develop and commercialize Ris-Rez outside mainland China, Hong Kong, Macau and Taiwan. The company is advancing a broad global clinical development program across lung cancer, prostate cancer and other solid tumors, including the Phase III EMBOLD SCLC-301 trial in relapsed extensive-stage SCLC, with pivotal data expected next year. Additional upcoming Phase III trials are planned in early-line SCLC and metastatic prostate cancers.
Ris-Rez targets the B7-H3 (搜索) protein, which is highly expressed in more than 10 solid tumor types, supporting an ambition to develop it across more than 40 indications by 2040. More than 1,000 patients have received Ris-Rez as part of GSK's global EMBOLD clinical trial program. The agent has received several global regulatory designations, including orphan drug designations in the US, Japan and the EU for SCLC, and Breakthrough Therapy Designation in the US and Priority Medicines (PRIME) Designation from the EMA for relapsed or refractory extensive-stage SCLC.
Disease Burden in SCLC
SCLC is associated with rapid progression and accounts for approximately 10-15% of all lung cancer diagnoses worldwide. It is characterized by early metastatic spread, frequent relapse and poor prognosis. Approximately 70% of patients with SCLC are diagnosed with extensive-stage disease (ES-SCLC), meaning the cancer has spread throughout one or both lungs and/or to other parts of the body. Median overall survival for patients with ES-SCLC treated with current standard-of-care therapies is approximately 12 to 13 months. Despite advances in treatment, outcomes for patients with ES-SCLC remain poor and the risk of disease progression or recurrence remains high, underscoring the need for new therapies.
The ARTEMIS-008 investigators concluded that Ris-Rez demonstrated a statistically significant and clinically meaningful OS benefit over topotecan in patients with SCLC that progressed after platinum-based therapy, with a favorable safety profile, suggesting the potential of Ris-Rez to define a new standard of care in relapsed SCLC.