GSK’227 Earns FDA Breakthrough Therapy Designation for Late-Line R/R Osteosarcoma

The FDA has granted breakthrough therapy designation to the B7-H3–targeted antibody-drug conjugate (ADC) GSK5764227 (GSK’227; HS-20093) for the treatment of adult patients with relapsed or refractory osteosarcoma whose disease has progressed on at least two prior lines of therapy.1

The designation was supported by findings from the phase 2 ARTEMIS-002 trial (NCT04502044), which was an open-label, randomized, multicenter study that investigated the efficacy and safety of GSK’227 in patients with relapsed/refractory osteosarcoma and other unresectable bone and soft tissue sarcomas.

Data from the phase 2 ARTEMIS-002 trial presented at the 2024 ASCO Annual Meeting demonstrated that at a median follow-up of 3.3 months, all evaluable patients with relapsed/refractory osteosarcoma (n = 38) experienced an overall response rate (ORR) of 10.5% (95% CI, 2.9%-21.1%) and a disease control rate (DCR) of 78.9% (95% CI, 62.7%-90.4%).2 In those treated with the 12.0-mg/kg dose of HS-20093 (n = 23), the ORR was 17.4% (95% CI, 5.0%-38.8%), and the DCR was 87.0% (95% CI, 66.4%-97.2%). In patients treated with GSK’227 at 8.0 mg/kg (n = 15), the ORR and DCR were 0% (95% CI, 0%-21.8%) and 66.7% (95% CI, 38.4%-88.2%), respectively.

“This latest regulatory designation for GSK’227 exemplifies the potential of our targeted ADC in patients with difficult-to-treat cancers. For patients with relapsed or refractory osteosarcoma, there is an urgent unmet medical need with no approved treatment options once the cancer returns a second time, and chemotherapy provides limited benefit in this setting,” Hesham Abdullah, senior vice president, global head oncology, R&D, at GSK, stated in a news release.1

The open-label, 2-arm ARTEMIS-002 trial enrolled patients at least 18 years of age with histologically confirmed osteosarcoma and other sarcomas whose disease progressed after at least 1 prior line of systemic therapy.2 Patients needed to have measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 to 1.

Cohort 1 included patients with osteosarcoma, and cohort 2 included patients with other sarcomas. In cohort 1, a total of 42 patients with osteosarcoma were assigned to receive GSK’227 at either 8.0 mg/kg (n = 16) or 12.0 mg/kg (n = 26) administered via intravenous infusion once every 3 weeks.

Investigator-assessed ORR was the trial’s primary end point. Secondary end points included independent review committee–assessed ORR; investigator-assessed DCR, duration of response, and progression-free survival; overall survival; and safety. B7-H3 expression was an exploratory end point.

Regarding safety, the most common treatment-emergent adverse effects (TEAEs) reported in at least 20% of patients included increased white blood cell count, decreased neutrophil count, anemia, fever, decreased platelet count, decreased lymphocyte count, nausea, vomiting, hypoalbuminemia, constipation, cough, hypocalcemia, decreased appetite, hypokalemia, and increased aspartate aminotransferase levels.

Beyond its current indication, GSK’227 has garnered additional regulatory designations.1 In August 2024, the FDA granted BTD for the agent in relapsed or refractory extensive-stage small-cell lung cancer, and the European Medicines Agency awarded priority medicines (PRIME) designation for the same indication in December 2024.

References

1. GSK’s B7-H3-targeted antibody-drug conjugate, GSK’227, receives US FDA breakthrough therapy designation in late-line relapsed or refractory osteosarcoma. News release. GSK. January 7, 2025. Accessed January 8, 2025. 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/
2. Xie L, Xu J, Sun X, et al. ARTEMIS-002: phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma. J Clin Oncol. 2024;42(suppl 16):11507. doi 10.1200/jco.2024.42.16_suppl.11507