Feature
Article
FDA Grants Breakthrough Therapy Designation to GSK’227 to Treat Osteosarcoma
Author(s):
Key Takeaways
- GSK5764227 targets B7-H3 and has shown promise in treating relapsed or refractory osteosarcoma, receiving FDA breakthrough therapy designation.
- Osteosarcoma is a rare, aggressive bone cancer with limited treatment options after two prior therapies, affecting mainly children and young adults.
The designation was supported by data from the phase 2, open-label, randomized, multi-center ARTEMIS-002 clinical trial, which assessed the safety and efficacy of GSK’227.
The FDA has granted breakthrough therapy designation for GSK5764227 (GSK’227, HS-20093; GSK), a B7-H3-targeted antibody drug conjugate (ADC), for the treatment of relapsed or refractory (R/R) osteosarcoma in adult patients who have progressed on at least 2 prior lines of therapy.1
Image credit: CHOI POO | stock.adobe.com
Osteosarcoma is a rare and aggressive bone cancer that occurs in the bone marrow. The cancer first starts in the ends of long bones around the knee, including the arms and legs. However, osteosarcoma can also occur in the upper leg, lower leg, or upper arm bone.1,2
According to Johns Hopkins Medicine, osteosarcoma is the most common primary bone cancer, accounting for 20% to 40% of all bone cancers. Osteosarcoma has an annual incidence of 3.3 patients per million in the US, mainly impacting children and young adults. Additionally, nearly 20% to 30% of patients with non-metastatic osteosarcoma and 80% with metastatic osteosarcoma experience R/R disease.1
The study authors noted that therapies are limited following 2 prior lines of treatment and there are currently no approved therapies — emphasizing the need for further treatment options.1
“For patients with [R/R] 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,” said Hesham Abdullah, senior vice president, global head oncology, R&D, GSK, in a news release.1
The novel investigational B7-H3-targeted antibody-drug conjugate, GSK’227 includes a fully human anti-B7-H3 monoclonal antibody that is connected to a topoisomerase inhibitor payload. The current breakthrough therapy designation marks the third designation for GSK’227, as it was granted priority medicines (PRIME) by the European Medicines Agency and breakthrough therapy designation by the FDA for refractory extensive-stage small-cell lung cancer in August 2024 and December 2024, respectively.1,3
The designation was supported by data from the phase 2, open-label, randomized, multi-center ARTEMIS-002 clinical trial (NCT05830123), which assessed the safety and efficacy of GSK’227 in patient with R/R osteosarcoma and other unresectable bone and soft tissue sarcomas. The study was conducted by Hansoh Pharma and included over 60 individuals—42 with osteosarcoma.1
Presented at the 2024 American Society of Clinical Oncology Annual Meeting, the results demonstrated that GSK’227 had an objective response rate of 20.0% at the 12.0 mg/kg dose and a disease control rate of 81.8% and 100% in the 8.0 mg/kg and 12.0 mg/kg groups, respectively. The study authors noted that common adverse events included hematological toxicities. GSK’277 exhibited dose-proportional pharmacokinetics with minimal accumulation. B7-H3, the target of GSK’277, was highly expressed in osteosarcoma, but no correlation with response was observed.4
“This latest regulatory designation for GSK’227 exemplifies the potential of our targeted ADC in patients with difficult to treat cancers,” said Abdullah, in a news release.1
