FDA Grants Breakthrough Therapy Designation to GSK’s Novel Treatment for Relapsed or Refractory Osteosarcoma

Image Credit: Adobe Stock Images/Joel bubble ben

The FDA has granted Breakthrough Therapy Designation (BTD) to GSK’s GSK5764227 (GSK’227) for treating adult patients with relapsed or refractory osteosarcoma who have progressed on at least two prior therapies. According to the company, this is the third regulatory designation for GSK’227, following the European Medicines Agency’s decision to grant Priority Medicines designation and the FDA’s decision to grant BTD for relapsed or refractory extensive-stage small-cell lung cancer in August 2024 and December 2024, respectively.¹

“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,” said Hesham Abdullah, SVP, global head oncology, R&D, GSK, in a press release.

ARTEMIS-002 consisted of 34 patients with relapsed or refractory osteosarcoma. As part of the trial, patients were randomly assigned to receive 8 mg/kg or 12 mg/kg every three weeks. At baseline, 94.1% had advanced disease and 82.4% had pulmonary metastases. Most patients had undergone prior treatments. Among 21 evaluable patients, the objective response rate (ORR) for the 12 mg/kg cohort was 20%, with two confirmed partial responses lasting up to four months. The disease control rate (DCR) was 81.8% in the 8 mg/kg group and 100% in the 12 mg/kg group; however, median progression-free survival was not yet mature.

Treatment-emergent adverse events were reported in 97.1% of patients, and included neutropenia, leukopenia, thrombocytopenia, lymphopenia, and anemia; however, none lead to death.²

According to the American Cancer Society, osteosarcoma is not a common cancer. On an annual basis, an estimated 1,000 new cases of osteosarcoma are diagnosed in the United States, while half of these cases are in children or adolescents. In most cases, osteosarcomas occur in children, teens, and young adults between 10 and 30 years of age. Teens are the most commonly affected groupbut people of any age can develop osteosarcoma. Every one in 10 cases reported are among individuals over 60 years of age. Two percent of all childhood cancers are osteosarcomas, but they make up a much smaller percentage of adult cancers.³

According to GSK, osteosarcomas account for 20% to 40% of all bone cancers and has an annual incidence of 3.3 patients per million in the United States. An estimated 20% to 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 patients with relapsed or refractory osteosarcoma are severely limited, with no clear standard of care available. Currently, options become even more limited after patients progress on two prior lines of treatment, as no therapies are currently approved by any regulatory body.¹

In 2024, it was estimated that there were 3,970 new cases of bone cancer diagnosed in the United States, with 2,050 deaths as a result. In adults, cancers that spread to the bones from other organs are considerably more common than primary bone cancers.⁴

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. January 7, 2025. Accessed January 7, 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. ARTEMIS-002: Phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma. ResearchGate. Accessed January 7, 2025. https://www.researchgate.net/publication/381424542_ARTEMIS-002_Phase_2_study_of_HS-20093_in_patients_with_relapsed_or_refractory_osteosarcoma

3. Key Statistics for Osteosarcoma. American Cancer Society. Accessed January 7, 2025. https://www.cancer.org/cancer/types/osteosarcoma/about/key-statistics.html

4. Key Statistics About Bone Cancer. American Cancer Society. Accessed January 7, 2025. https://www.cancer.org/cancer/types/bone-cancer/about/key-statistics.html