FDA Grants Breakthrough Therapy Designation to GSK for Small-Cell Lung Cancer Treatment

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GSK announced in a press release on Aug. 20, 2024 that it has received a Breakthrough Therapy designation from FDA for GSK5764227 (GSK’227), an investigational antibody-drug conjugate (ADC) that targets the B7-H3 protein, also known as CD276 (1,2). B7-H3 is thought to be a valuable target for cancer therapy, and GSK’227 has been under evaluation for the treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC) who are experiencing either relapsed or refractory disease progression following platinum-based chemotherapy (1,2).

Breakthrough Therapy is granted by FDA based on certain drug company requests and is intended to expedite the development and review processes when a drug is being designed to treat a serious condition, and preliminary clinical evidence has shown that it may demonstrate a substantial improvement over previously existing therapies (1,3). Determining factors may include the magnitude and duration of the treatment effect, and a “clinically significant” endpoint which measures an effect on irreversible morbidity or mortality (3).

According to GSK, lung cancer is one of the most common cancers in the world, and in the United States, approximately 15% of all lung cancers are of the small-cell variety (1). Of those, 70% are classified as ES-SCLC—meaning that the cancer has spread throughout at least one lung if not both, and/or to other parts of the body. The five-year survival rate for ES-SCLC is currently approximately 3%; however, most patients relapse after their initial treatment, and the median overall duration of survival with the standard-of-care treatments that have been available to date is between five and six months.

“Extensive-stage small-cell lung cancer is aggressive with poor prognosis and significant need for new treatments,” Hesham Abdullah, GSK senior vice president and global head of oncology R&D, said in the press release. “Today’s Breakthrough Therapy Designation supports our ambition to accelerate GSK’227 for these patients as part of our broader ADC program focused on developing new treatment options with transformational and first-to-market potential.”

In December 2023, GSK entered an exclusive license agreement with Hong Kong-based Hansoh Pharma to develop and commercialize its HS-20093, which has since been rechristened GSK’227 (4).

“B7-H3 is highly expressed in a broad range of solid tumors where there remains a significant need for novel treatment options,” Abdullah said at the time. “We look forward to progressing this potential new treatment across several indications and in future potential combination approaches with our established portfolio.”

A Phase I trial (ARTEMIS-001) for GSK’227, upon which FDA’s Breakthrough Therapy designation was based, is still ongoing, but results thus far will be presented at the 2024 World Conference on Lung Cancer in San Diego, Ca. from Sept. 7–10, 2024 (1).

References

1. GSK. GSK Receives US FDA Breakthrough Therapy Designation for Its B7-H3-Targeted Antibody-Drug Conjugate in Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer. Press Release. Aug. 20, 2024.
2. Yang, S.; Wei, W.; and Zhao, Q. B7-H3, A Checkpoint Molecule, As a Target for Cancer Immunotherapy. Int. J. Biol. Sci. 2020, 16 (11) 1767–1773. DOI: 10.7150/ijbs.41105
3. FDA. Breakthrough Therapy. FDA.gov/patients, Jan. 4, 2018 (accessed Aug. 20, 2024).
4. GSK. GSK Enters Exclusive License Agreement with Hansoh for HS-20093. Press Release. Dec. 20, 2023.