Ris-Rez Cuts Death Risk 54% Versus Topotecan in Relapsed SCLC, First Phase III OS Win for a B7-H3 ADC
核心洞察
GSK and Hansoh reported that the B7-H3 (搜索)-targeted antibody-drug conjugate risvutatug rezetecan (搜索) reduced the risk of death by 54% versus topotecan in relapsed small cell lung cancer (搜索).
In the phase III ARTEMIS-008 trial, median overall survival reached 18.5 months with Ris-Rez versus 10.3 months with topotecan after a median 12.2 months of follow-up.
Secondary endpoints favored Ris-Rez, with median progression-free survival of 7.2 versus 3.0 months and objective response rates of 58.3% versus 12.6%.
GSK and its licensor Hansoh Pharmaceutical Group (搜索) reported that the B7-H3 (搜索)-targeted 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 (搜索) (SCLC) whose disease progressed on or after first-line platinum-based therapy. The results from the pivotal phase III ARTEMIS-008 trial, first announced in July, were presented in a Presidential Symposium session at the 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea, and represent the first phase III data to demonstrate an overall survival (OS) benefit for a B7-H3 ADC in any tumour type.
At a median follow-up of 12.2 months and a June 6, 2026 data cutoff, Ris-Rez met the trial's primary endpoint, reducing the risk of death by 54% versus topotecan (HR 0.46; 95% CI: 0.35–0.62, p<0.0001). Patients receiving Ris-Rez lived a median of 18.5 months (n=230) compared with 10.3 months for those receiving topotecan (n=231). Twelve-month overall survival rates were 64.5% versus 43.3%, respectively, and the survival benefit was consistent across prespecified subgroups.
Secondary Endpoints Favor Ris-Rez
The OS benefit was supported by improvements across key secondary efficacy endpoints assessed by blinded independent central review. Median progression-free survival was 7.2 months versus 3.0 months (HR 0.33; 95% CI: 0.25–0.42); objective response rate was 58.3% versus 12.6%; and disease control rate was 90.4% versus 60.2% for Ris-Rez and topotecan, respectively. Investigator-assessed outcomes were consistent with the central review findings.
"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," said Professor Jie Wang, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences Peking Union Medical College, and principal investigator of ARTEMIS-008. "These results suggest the potential of Ris-Rez to define a new standard of care in relapsed SCLC."
Safety Profile
Patients receiving Ris-Rez experienced fewer severe treatment-related adverse events (TRAEs) than those receiving topotecan, with grade 3 or higher TRAEs occurring in 60.9% versus 78.2% of patients, respectively. The most common grade 3 or higher TRAEs with Ris-Rez were decreased neutrophils, decreased white blood cells, anaemia, decreased lymphocytes and decreased platelets. These haematologic TRAEs are considered manageable and consistent with the known side effects in this class of medicines.
"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."
Trial Design and Patient Population
ARTEMIS-008 (NCT06498479) is Hansoh's multicentre, randomised, open-label, active-controlled phase III trial evaluating Ris-Rez versus topotecan in patients in China with limited- or extensive-stage SCLC whose disease progressed on or after first-line platinum-based therapy. A total of 461 patients were randomised 1:1 to receive Ris-Rez 8.0 mg/kg intravenously every three weeks or topotecan 1.2 mg/m² on days 1–5 of each 21-day cycle. More than 80% of patients had previously received PD-(L)1 inhibitors. The primary endpoint was a statistically significant and clinically meaningful improvement in overall survival; secondary endpoints included progression-free survival, objective response rate, disease control rate, duration of response and safety.
Mechanism and Earlier-Phase Data
Risvutatug rezetecan (搜索) (HS-20093, GSK5764227) is a B7-H3 (搜索)-directed ADC discovered by Hansoh Pharmaceutical, comprising a fully human anti-B7-H3 monoclonal antibody conjugated to rezetecan, an exatecan-derived topoisomerase I inhibitor payload, via a tetrapeptide-based cleavable linker. The same payload class underlies several other ADCs from Chinese biopharmaceutical developers directed against unrelated targets, including the HER2-directed trastuzumab rezetecan (SHR-A1811) and the B7-H4-directed mocertatug rezetecan (搜索) (GSK5733584, also GSK-partnered).
B7-H3 (搜索), also known as CD276 (搜索), is a transmembrane immune checkpoint protein of the B7 family characterised by broad tumour overexpression alongside minimal normal-tissue protein expression — a discordance attributed to post-transcriptional regulation by microRNAs of the miR-29 family. In tumours, this regulatory constraint is lost, resulting in marked protein overexpression across more than ten solid tumour types, including small cell and non-small cell lung cancer (搜索), prostate cancer, osteosarcoma (搜索) and various sarcomas. Despite more than two decades of study, researchers have not identified a definitive receptor for B7-H3.
Foundational phase Ia/Ib data from the ARTEMIS-001 trial (NCT05276609), conducted in 306 patients with previously treated advanced solid tumours, established a maximum tolerated dose of 12.0 mg/kg and confirmed antitumour activity in lung cancer, with confirmed objective response rates of 50–54% among SCLC patients across the 8.0 and 10.0 mg/kg dose levels. Among 236 lung cancer patients treated at these dose levels, treatment-related interstitial lung disease occurred in 3.4% and adverse events leading to death occurred in 3.8%. A separate phase I cohort in NSCLC reported a confirmed objective response rate of 33.3% among patients with non-squamous disease without actionable genomic alterations at the 8.0 mg/kg dose.
Development Programme and Regulatory Designations
Under a December 2023 licence agreement, GSK holds exclusive rights to develop and commercialise Ris-Rez outside mainland China, Hong Kong, Macau and Taiwan, while Hansoh retains rights within these territories and plans to pursue a regulatory submission in China based on the ARTEMIS-008 data. GSK's global EMBOLD programme has enrolled more than 1,000 patients and includes the phase III EMBOLD SCLC-301 trial (NCT07099898) in relapsed extensive-stage SCLC outside China, with pivotal data expected next year, along with planned phase III trials in earlier-line SCLC and metastatic prostate cancer. GSK has stated an ambition to develop Ris-Rez across more than 40 indications by 2040.
Ris-Rez has received several global regulatory designations, including orphan drug designations in the US, Japan and the EU for SCLC, Breakthrough Therapy Designation in the US for relapsed or refractory extensive-stage SCLC and for late-line relapsed or refractory osteosarcoma (搜索), and Priority Medicines (PRIME) designation from the EMA for relapsed extensive-stage SCLC.
"These results add to the growing body of evidence for Ris-Rez and mark an important step forward for our lung cancer portfolio," said Hesham Abdullah, Senior Vice President, Global Head of Oncology, R&D, GSK. "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)."
Disease Burden and Unmet Need
SCLC is a high-grade neuroendocrine malignancy associated with rapid progression, early metastatic spread, frequent relapse and poor prognosis, accounting for approximately 10–15% of all lung cancer diagnoses worldwide, with an estimated incidence of 4.7 cases per 100,000 individuals and five-year overall survival ranging from 12% to 30%. Approximately 70% of patients 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, and outcomes deteriorate substantially after relapse, when few therapies have demonstrated a durable survival benefit. Topotecan remains among the most widely used agents in the relapsed setting but is associated with modest response rates and substantial haematologic toxicity.
Competitive Landscape in B7-H3-Directed Therapy
Ris-Rez enters a competitive field of B7-H3 (搜索)-targeted therapeutics. Ifinatamab deruxtecan (I-DXd; DS-7300A), developed by Daiichi Sankyo and jointly advanced with Merck (搜索), is the most clinically advanced rival programme, comprising a humanised anti-B7-H3 monoclonal antibody conjugated to an exatecan-derived topoisomerase I inhibitor via a tetrapeptide-based cleavable linker. It has reported an objective response rate of approximately 48–55% and a median overall survival of approximately 10–12 months in pretreated extensive-stage SCLC across its phase 1/2 and phase II IDeate-Lung01 (NCT05280470) programmes. The FDA accepted a biologics license application for ifinatamab deruxtecan in this setting in 2026 under priority review, following Breakthrough Therapy Designation granted in 2025; the agent has also been associated with interstitial lung disease.
Earlier-stage B7-H3 (搜索)-directed ADCs from Chinese developers include YL201, which has reported disease control rates above 80% and objective response rates of approximately 64% in extensive-stage SCLC and 49% in nasopharyngeal carcinoma in early-phase testing; DB-1311 (BNT324), developed by DualityBio with BioNTech; MHB088C; and 7MW3711 (Mabwell), which has reported an objective response rate exceeding 60% in a small SCLC cohort. AbbVie's mirzotamab clezutoclax (ABBV-155), which conjugates a B7-H3-targeted antibody to a BCL-XL inhibitor payload, has reported more modest response rates in SCLC, NSCLC and breast cancer cohorts, while MacroGenics' MGC026, a SYNtecan E-based B7-H3 ADC, remains in early clinical evaluation (NCT06242470).
Other programmes have encountered setbacks. Vobramitamab duocarmazine (MGC018), a MacroGenics ADC pairing a B7-H3 (搜索)-targeted antibody with a DNA-alkylating duocarmycin payload, was discontinued for company-sponsored development following a 2024 review of phase II data in metastatic castration-resistant prostate cancer (搜索), after an independent safety monitoring committee recommended halting treatment for safety reasons. Earlier non-ADC approaches also faced challenges: the monoclonal antibody enoblituzumab (MGA271) was halted after drug-related mortality in a phase II head and neck cancer trial, and the CD3/B7-H3 bispecific DART molecule MGD009 was terminated in a phase I trial due to hepatotoxicity.
B7-H3 (搜索) is also being pursued through CAR T-cell approaches. A preclinical study from St. Jude Children's Research Hospital published in August 2026 reported that deletion of the inhibitory ribonuclease Regnase-1 (搜索) in B7-H3-directed CAR T cells improved tumour control and prevented pulmonary metastasis in mouse models of osteosarcoma (搜索), an indication in which Ris-Rez has separately received Breakthrough Therapy Designation, with the engineered cells advancing toward an early-phase clinical trial.
A Parallel Readout in Relapsed SCLC
A second randomised phase III trial in relapsed SCLC, TAISHAN-302, also reported positive results at WCLC 2026. As summarised by Gilberto Lopes, Chief of the Division of Medical Oncology at Sylvester Comprehensive Cancer Center, tambotatug pelitecan (搜索) (Tam-Peli) versus topotecan produced overall survival of 13.3 versus 9.4 months (HR 0.46), progression-free survival of 7.4 versus 2.8 months (HR 0.29), objective response rates of 59.1% versus 9.7%, intracranial response rates of 32% versus 3%, and grade 3 or higher adverse events in 55.4% versus 77.9% of patients. Lopes described the trial as "a major positive randomized phase 3 trial and a potential new 2L option in SCLC," while noting that it was a China-only study, that broader global validation still matters, and that sequencing versus tarlatamab remains an open question.