GSK's investigational antibody-drug conjugate (ADC), GSK'227, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory osteosarcoma who have progressed on at least two prior lines of therapy. This regulatory designation, announced by GSK on Tuesday, aims to accelerate the development and review of this promising treatment for a rare and aggressive bone cancer that currently lacks approved therapies after initial treatments fail.
The FDA's decision was supported by data from the ARTEMIS-002 study, a phase II, open-label, randomized, multi-center clinical trial conducted by Hansoh Pharma. The trial evaluated the efficacy and safety of GSK'227 in patients with relapsed or refractory osteosarcoma and other unresectable bone and soft tissue sarcomas. Results from ARTEMIS-002 were presented at the 2024 American Society of Clinical Oncology Annual Meeting, demonstrating promising activity in osteosarcoma patients.
Addressing Unmet Needs in Osteosarcoma
Osteosarcoma primarily affects children and young adults and is the most common primary bone cancer, accounting for 20-40% of all bone cancers. However, it remains a rare disease, with an annual incidence of 3.3 patients per million in the US, representing less than 1% of all new cancer diagnoses. Approximately 20-30% of patients who present with localized (non-metastatic) osteosarcoma and 80% of those who present with metastatic osteosarcoma experience relapsed or refractory disease. Following first-line chemotherapy, treatment options for these patients are severely limited, with no clear standard of care available, and no approved therapies after patients progress on two prior lines of treatment.
"This latest regulatory designation for GSK'227 exemplifies the potential of our targeted ADC in patients with difficult to treat cancers," said Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK. "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."
About GSK'227
GSK'227, also known as HS-20093, is a novel investigational B7-H3-targeted antibody-drug conjugate composed of a fully human anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor payload. B7-H3 is a protein expressed in various cancers. HS-20093 is being developed by Hansoh Pharma for the treatment of lung cancer, sarcoma, head and neck cancers and other solid tumours in multiple phase I, II and III clinical trials in China. GSK's global phase I trial for GSK'227 began in August 2024 (NCT06551142) as a part of the development plan to support a registrational pathway for GSK'227.
ARTEMIS-002 Trial Details
The ARTEMIS-002 trial is a phase II, open-label, randomised, multi-centre, clinical trial evaluating the efficacy and safety of GSK'227 in patients with relapsed or refractory osteosarcoma and other unresectable bone and soft tissue sarcomas. More than 60 patients were enrolled, including 42 patients with osteosarcoma. In the osteosarcoma cohort of the trial (n = 42), patients were randomly assigned, in a 1:1 ratio, to receive either 8.0 mg/kg (n = 16) of GSK’227 or 12.0 mg/kg (n = 26), with both treatments given every 3 weeks. Eligible patients were 18 years or older with histologically confirmed osteosarcoma or other sarcomas who had progressed on 1 or more lines of prior systemic treatment, had at least one measurable lesion per RECIST 1.1 and an ECOG performance status of 0 or 1, and agreed to provide fresh or archival tumor tissue and peripheral blood samples.
The trial’s primary end point was ORR per investigator. Secondary end points were ORR per independent review committee, DCR, DOR, and PFS per investigator, overall survival, and safety.
Additional Regulatory Designations
This is the third regulatory designation for GSK'227, following the European Medicines Agency's decision to grant Priority Medicines (PRIME) designation and the FDA's decision to grant Breakthrough Therapy Designation for relapsed or refractory extensive-stage small-cell lung cancer in August 2024 and December 2024, respectively.
