Risvutatug rezetecan

Overview

Risvutatug rezetecan (HS-20093; GSK5764227; GSK’227) is an investigational antibody–drug conjugate (ADC) targeting B7-H3, under development for multiple solid tumors. Clinical development is most advanced in relapsed small-cell lung cancer (SCLC), where a randomized phase 3 trial conducted in China has reported positive survival results. Earlier studies have also shown activity in non-small-cell lung cancer (NSCLC), sarcomas and metastatic castration-resistant prostate cancer (mCRPC). (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

The ADC consists of a fully human anti–B7-H3 monoclonal antibody linked through a protease-cleavable linker to a topoisomerase I inhibitor payload; its reported drug-to-antibody ratio is 4. B7-H3 is expressed across numerous solid tumors but more narrowly in normal tissues. After binding and internalization, the ADC is designed to release its cytotoxic payload within tumor cells, causing DNA damage. (ascopubs.org)

Efficacy

In ARTEMIS-008, 461 Chinese patients with SCLC progressing on or after platinum-based treatment were randomized to risvutatug rezetecan 8 mg/kg every three weeks or topotecan. At the June 6, 2026 cutoff:

• Median overall survival was 18.5 versus 10.3 months (hazard ratio 0.46; 95% CI 0.35–0.62).
• Median progression-free survival was 7.2 versus 3.0 months.
• Objective response rates were 58.3% versus 12.6%.
• Disease-control rates were 90.4% versus 60.2%.

More than 80% of participants had previously received a PD-(L)1 inhibitor. These results were presented at the 2026 World Conference on Lung Cancer and had not yet been reported in a peer-reviewed full publication at the time of presentation. (iaslc.org)

In the phase 1 ARTEMIS-001 study, confirmed response rates among response-evaluable patients treated at 8 or 10 mg/kg were 52.3% in extensive-stage SCLC and 22.4% in NSCLC. The 8-mg/kg dose was selected for phase 3 development. (pubmed.ncbi.nlm.nih.gov)

Additional early findings include:

• Relapsed/refractory osteosarcoma: response rates of 6.7% at 8 mg/kg and 17.2% at 12 mg/kg, with median progression-free survival of 4.0 and 8.4 months, respectively.
• Other relapsed/refractory sarcomas: response rate 25.0% and median progression-free survival 8.2 months.
• mCRPC: confirmed response rate 33.3% among 33 patients with measurable disease; confirmed PSA₅₀ response rate 32.0% among all 50 treated patients. (annalsofoncology.org)

Cross-trial comparisons are not appropriate because the studies differed in disease, dose, eligibility and follow-up.

Safety

Toxicity is predominantly hematologic. In ARTEMIS-008, grade 3 or higher treatment-related adverse events occurred in 60.9% of risvutatug rezetecan recipients versus 78.2% with topotecan; common severe events included neutropenia, leukopenia, anemia, lymphopenia and thrombocytopenia. (iaslc.org)

In ARTEMIS-001, grade 3 or higher neutrophil-count decreases occurred in 25.5% at 8 mg/kg and 50.5% at 10 mg/kg; corresponding anemia rates were 16.8% and 34.3%. Treatment-related interstitial lung disease occurred in 3.4% of patients, and treatment-related adverse events resulting in death occurred in 3.8%, making pulmonary and hematologic toxicity important risks for continued evaluation. (pubmed.ncbi.nlm.nih.gov)

Further reading

• ARTEMIS-001 phase 1 results in Cancer Cell
• ARTEMIS-008 phase 3 results reported by the IASLC
• ARTEMIS-002 phase 2 sarcoma abstract in Annals of Oncology
• ARTEMIS-003 phase 2 mCRPC abstract in the Journal of Clinical Oncology

Last updated: Sep 2026