The Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to treatment with GSK’227 (GSK5764227; HS-20093), a B7-H3-targeted antibody-drug conjugate (ADC), for the treatment of adult patients with relapsed or refractory osteosarcoma, a kind of bone cancer, who have progressed on at least two prior lines of therapy, according to a press release from GSK plc.
The regulatory decision is supported by data from the phase 2 ARTEMIS-002 study, in which more than 60 patients with relapsed or refractory osteosarcoma (42 patients) and other unresectable bone and soft tissue sarcomas were evaluated. Notably, this open-label, randomized, multi-center clinical trial was conducted by Hansoh Pharma and initial results from ARTEMIS-002 were presented at the 2024 ASCO Annual Meeting.
“This latest regulatory designation for GSK’227 exemplifies the potential of our targeted ADC in patients with difficult to treat cancers,” Hesham Abdullah, Senior Vice President and Global Head Oncology, R&D, GSK, said in the press release. “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.”
Glossary:
Antibody-drug conjugate (ADC): a therapeutic agent that combines a monoclonal antibody with a cytotoxic drug to treat cancer.
Breakthrough therapy designation (BTD): a process that speeds up the development and review of drugs that treat serious or life-threatening conditions.
Confirmed partial response: a patient's tumor has demonstrably shrunk by a significant amount.
Disease control rate: the percentage of patients with advanced cancer who have a complete response, partial response or stable disease after treatment.
Overall response rate: how many patients experienced a significant shrinkage or disappearance of their tumors after treatment.
The Food and Drug Administration (FDA): a federal agency that protects the public's health.
From June to December of 2023, 34 patients with relapsed or refractory osteosarcoma received GSK’227 at a dose of either 8 mg/kg (15 patients) or 12 mg/kg (19 patients). Notably, most of these patients had clinical stage 4 disease and pulmonary metastasis; twenty-two of whom had also received three or more prior therapies and 26 had received four types of standard chemotherapies, making these heavily pretreated patients.
The median follow-up time was 4.1 months at a data cutoff data of Dec. 25, 2023, among 21 response-evaluable patients. At the 12 mg/kg dosing schedule, the overall response rate was 20%, consisting of two participants with confirmed partial responses who remained on response until last follow-up, of which the longest duration of response was four months. The disease control rate in the 12 mg/kg dosing schedule was 100%, while it was 81.8% in the 8 mg/kg group.
Overall, investigators noted that the data showed antitumor activity with acceptable toxicity in patients with relapsed or refractory osteosarcoma and enrollment is ongoing.
Delving into the Importance of Ongoing Research With GSK’227
Osteosarcoma remains the most common primary bone cancer, as it accounts for 20% to 40% of all bone cancers and primarily manifests in children and young adults. However, the disease is rare and has an annual incidence of 3.3 patients per million in the United States and represents less than 1% of all new cancer diagnoses every year. In total, 20% to 30% of patients who are diagnosed with the rare disease present with localized or non-metastatic osteosarcoma and 80% of those individuals experience relapsed or refractory disease.
Despite a high incidence of relapsed disease, treatment options for patients with osteosarcoma are limited and no clear standard of care is available following first-line chemotherapy. Moreover, following progression on two prior lines of treatment, there are no approved treatment options as approaches become even more limited.
The novel investigational B7-H3-targeted ADC, GSK’227, is composed of a fully human anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor payload and may serve as a potential treatment option for this underserved population. The investigational agent is currently being developed for the treatment of lung cancer, head and neck cancers and other solid tumors — in addition to sarcoma — in multiple phase 1, 2 and 3 clinical trials in China.
The release goes on to state that the BTD is the third regulatory designation for GSK’227. Prior designations for the ADC include the European Medicines Agency’s decision to grant Priority Medicines designation to GSK’227 and the FDA’s regulatory decision to grant BTD to the agent for relapsed or refractory extensive-stage small cell lung cancer, both in 2024.
Furthermore, the company noted that exclusive worldwide rights were acquired from Hansoh Pharma to progress clinical development and commercialization of GSK’227, which has led to a GSK-initiated global phase 1 trial as a part of the development plan for GSK’227.
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