GSK’227 Wins FDA Orphan Drug Designation in Small-Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to GSK’227, now known as risvutatug rezetecan, for the treatment of small-cell lung cancer (SCLC), according to a news release from GSK plc, a global biopharma company.

This regulatory designation was supported by early clinical findings showing durable responses in some patients with extensive-stage SCLC (ES-SCLC), a particularly aggressive form of the disease with limited treatment options, the news release continued.

Orphan drug designation is a status granted by the FDA to therapies being developed for rare diseases that affect fewer than 200,000 people in the United States, according to the FDA website. The designation provides regulatory incentives to encourage development of treatments for conditions that might otherwise lack commercial viability, although it does not guarantee the approval of the agent by the FDA.

The decision marks another regulatory milestone for risvutatug rezetecan, a B7-H3-targeted antibody-drug conjugate being developed by GSK. According to the company, this is the fifth regulatory designation awarded to the therapy, reinforcing plans to accelerate its development across multiple solid tumors with high unmet medical need.

The orphan drug designation was based on preliminary results from the phase 1 ARTEMIS-001 clinical trial, which evaluated risvutatug rezetecan in patients with ES-SCLC. Investigators reported durable responses in some patients, which is important given this is a disease where relapse is common and long-term disease control is rare.

Regulatory Designation Highlights Urgent Need for New SCLC Treatments

SCLC accounts for approximately 13% of all lung cancer diagnoses in the United States, with an estimated 29,500 new cases expected in 2025, according to the news release. Approximately 70% of patients are diagnosed with extensive-stage disease, meaning the cancer has spread beyond one lung or to other parts of the body.

ES-SCLC is known for its rapid growth, early spread and high likelihood of recurrence after initial therapy, the release continued. The five-year survival rate for ES-SCLC is approximately 3%, and most patients relapse following first-line treatment. Median overall survival after relapse with current standard therapies is approximately eight months,

Based on these current unmet needs for patients with ES-SCLC, new therapeutic approaches are urgently needed.

Early Clinical Signals of Risvutatug Rezetecan

The FDA decision follows a recent orphan drug designation granted by the European Medicines Agency for risvutatug rezetecan in pulmonary neuroendocrine carcinoma, a broader cancer category that includes SCLC. Previously, the therapy also received priority medicines (PRIME) designation from the European Medicines Agency for relapsed or refractory ES-SCLC, as well as breakthrough therapy designations from the FDA for relapsed or refractory ES-SCLC and relapsed or refractory osteosarcoma.

Risvutatug rezetecan is an investigational antibody-drug conjugate designed to target B7-H3, a protein expressed on the surface of certain cancer cells. The therapy combines a fully human monoclonal antibody directed against B7-H3 with a chemotherapy payload that inhibits topoisomerase, an enzyme involved in DNA replication. By delivering the payload directly to cancer cells, the approach is intended to maximize anti-tumor activity and limit damage to healthy tissue.

Next Steps in the Clinical Investigation of Risvutatug Rezetecan

Importantly, for patients with SCLC, GSK initiated a global phase 3 clinical trial of risvutatug rezetecan in relapsed ES-SCLC in August 2025. Results from this study will be critical in determining whether the early signals of benefit translate into meaningful improvements in outcomes for patients with this disease, the news release concluded.

References

1. “GSK’227, a B7-H3-targeted antibody-drug conjugate, granted Orphan Drug Designation in small-cell lung cancer by the US FDA,” by GSK plc. News release; Dec. 10, 2025.
2. “Medical products for rare diseases and conditions,” by the U.S. FDA. Jan. 10, 2024. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions

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