Investigational Drug
GSK5764227
TrialFetch AI Analysis
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Overview
GSK5764227 (HS-20093) is an investigational, B7‑H3–targeted antibody–drug conjugate (ADC) licensed by GSK from Hansoh Pharma in December 2023 for development outside Greater China. It is in global phase 1 development (NCT06551142) and is being studied in China in phase 1/2 trials across multiple solid tumors, including small cell lung cancer (SCLC) and sarcomas. In 2024–2025 it received FDA Breakthrough Therapy Designation (BTD) for relapsed/refractory extensive‑stage SCLC (August 20, 2024) and for late‑line relapsed/refractory osteosarcoma (January 7, 2025). China’s NMPA also granted Breakthrough‑Therapy designation for ES‑SCLC in November 2024. (gsk.com)
Mechanism of action
GSK5764227/HS‑20093 is a fully humanized anti–B7‑H3 ADC that delivers a DNA topoisomerase I inhibitor payload via intravenous dosing every 3 weeks. B7‑H3 (CD276) is broadly expressed across solid tumors with limited expression in normal tissues; the ADC internalizes upon target binding to release cytotoxic payload inside tumor cells. (gsk.com)
Clinical development
- Global: First‑in‑human, multi‑part phase 1 study sponsored by GSK (NCT06551142) is recruiting, including monotherapy dose escalation/expansion and combination cohorts with chemotherapy and immunotherapy. (cdek.pharmacy.purdue.edu)
- China: ARTEMIS‑001 (phase 1, NCT05276609) in advanced solid tumors; ARTEMIS‑002 (phase 2, NCT05830123) in relapsed/refractory osteosarcoma and other sarcomas. (cdek.pharmacy.purdue.edu)
Efficacy
Small cell lung cancer (ES‑SCLC), relapsed/refractory
- Phase 1 ARTEMIS‑001 expansion (randomized to 8 vs 10 mg/kg Q3W): as of June 30, 2024, overall response rate (ORR) was 61.3% (n=31) at 8 mg/kg and 50.0% (n=22) at 10 mg/kg; median PFS 5.9 and 7.3 months, respectively. Responses were observed regardless of B7‑H3 expression in the program. These results were presented at WCLC 2024 and ASCO 2024 (abstract 8093). (hspharm.com)
- Earlier dose‑escalation (through Dec 20, 2022): among 40 response‑evaluable patients across tumors, ORR was 35% with disease control rate (DCR) 85%; in a nine‑patient SCLC subset, ORR was 77.8%. (ascopubs.org)
Osteosarcoma and other sarcomas
- Phase 2 ARTEMIS‑002 (ASCO 2024, abstract 11507): in osteosarcoma randomized to 8 vs 12 mg/kg, ORR at 12 mg/kg was 20.0%; DCR 100% (10/10) at 12 mg/kg and 81.8% (9/11) at 8 mg/kg; median PFS not yet mature at data cutoff. In “other sarcomas” (single‑arm 12 mg/kg), ORR 25% and median PFS 7.1 months (interim). (ascopubs.org)
Notes: GSK reported FDA BTD based on preliminary clinical evidence in ES‑SCLC (Aug 2024) and in osteosarcoma (Jan 2025). (gsk.com)
Safety
Across early studies, the most frequent treatment‑emergent or treatment‑related grade ≥3 adverse events are hematologic, including neutropenia, leukopenia, anemia, lymphopenia, and thrombocytopenia. In ARTEMIS‑001 dose escalation, the maximum tolerated dose was 12 mg/kg; dose‑limiting toxicities occurred at 12–16 mg/kg. Notably, interstitial lung disease was not reported in the 2023 dose‑escalation abstract. Safety in expansion cohorts was described as consistent with earlier reports. (ascopubs.org)
Further reading
- ASCO 2023 phase 1 abstract (ARTEMIS‑001, dose escalation): https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3017 (ascopubs.org)
- ASCO 2024 abstract (ARTEMIS‑001 SCLC expansion, 8 vs 10 mg/kg): via Ovid listing https://www.ovid.com/journals/jclon/abstract/10.1200/jco.2024.42.16_suppl.8093 (ovid.com)
- WCLC 2024 update (company summary of ARTEMIS‑001 SCLC cohort): https://www.hspharm.com/news/news-detail-513214.htm (hspharm.com)
- ASCO 2024 abstract (ARTEMIS‑002 osteosarcoma): https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.11507 (ascopubs.org)
- FDA BTD (ES‑SCLC): https://www.gsk.com/en-gb/media/press-releases/gsk-receives-us-fda-breakthrough-therapy-designation/ (gsk.com)
- FDA BTD (osteosarcoma): https://www.gsk.com/en-gb/media/press-releases/gsk-b7-h3-targeted-antibody-drug-conjugate-gsk227-receives-us-fda-breakthrough-therapy-designation-in-late-line-relapsed-or-refractory-osteosarcoma/ (gsk.com)
- NMPA Breakthrough‑Therapy designation (ES‑SCLC): https://www.hspharm.com/news/news-detail-513241.htm (hspharm.com)
- GSK–Hansoh license announcement (mechanism and program scope): https://www.gsk.com/en-gb/media/press-releases/gsk-enters-exclusive-license-agreement-with-hansoh-for-hs-20093/ (gsk.com)
- Global phase 1 trial record (NCT06551142): https://cdek.pharmacy.purdue.edu/trial/NCT06551142/ (cdek.pharmacy.purdue.edu)
- China phase 1 and phase 2 trial records (NCT05276609; NCT05830123): https://cdek.pharmacy.purdue.edu/trial/NCT05276609/ and https://cdek.pharmacy.purdue.edu/trial/NCT05830123/ (cdek.pharmacy.purdue.edu)
Disclaimer: Findings are from early‑phase studies and meeting abstracts; efficacy and safety profiles remain investigational and may evolve with ongoing trials. (ovid.com)
Last updated: Oct 2025
Active trials using GSK5764227
Found 3 active trials using this drug:
TrialFetch AI summary: Enrolls adults (ECOG 0–1) with unresectable/metastatic colorectal adenocarcinoma or metastatic castration-resistant prostate cancer. Tests the B7-H3–targeted antibody-drug conjugate GSK5764227 (anti–B7-H3 mAb linked to a topoisomerase inhibitor payload) in combination with bevacizumab ± 5-FU/leucovorin for metastatic CRC, or with enzalutamide for mCRPC.
ClinicalTrials.gov ID: NCT07277270
TrialFetch AI summary: Adults with unresectable or metastatic colorectal cancer (after 1–2 prior lines) or pancreatic ductal adenocarcinoma (after exactly 1 prior line), ECOG 0–1, receive monotherapy GSK5764227 (HS-20093), a B7-H3–targeted antibody-drug conjugate delivering a topoisomerase I inhibitor, at cohort-specific dose levels. Excludes active CNS mets, significant cardiovascular/hepatic/renal disease, prior topo‑I ADCs, and viral hepatitis; tumor tissue required for CRC and requested for PDAC.
ClinicalTrials.gov ID: NCT06885034
TrialFetch AI summary: This trial investigates GSK4381562, a monoclonal antibody targeting PVRIG to enhance NK and T cell activation, as monotherapy and in combination with anticancer agents such as dostarlimab, belrestotug, nelistotug, and GSK5764227 in patients with advanced solid tumors who lack standard treatment options. Eligible participants have locally recurrent or metastatic solid tumors, have progressed after standard therapies, and possess an ECOG performance status of 0-1 with adequate organ function.
ClinicalTrials.gov ID: NCT05277051
