FDA Grants Breakthrough Therapy Designation to GSK’s GSK5764227 for Relapsed or Refractory Extensive-Stage Small-Cell Lung Cancer

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The FDA has granted Breakthrough Therapy Designation to GSK’s GSK5764227 (HS-20093; GSK’227) an investigational antibody-drug conjugate (ADC) for relapsed or refractory extensive-stage small-cell lung cancer (ES-SCLC). According to the company, the Breakthrough Therapy Designation was based on preliminary data from the ongoing ARTEMIS-001 Phase I trial, which evaluated over 200 patients with solid tumors, including ES-SCLC. Earlier this year, GSK acquired global rights to GSK’277 from Hansoh Pharma. Full results from the trial are expected to be presented at the 2024 World Conference on Lung Cancer in September and GSK plans to initiate global Phase I/II trials later this year to support regulatory approval.¹

“Extensive-stage small-cell lung cancer is aggressive with poor prognosis and significant need for new treatments. 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,” said Hesham Abdullah, SVP, global head oncology, R&D, GSK, in a press release.

ARTEMIS-001 enrolled patients with multiple types of tumors, including SCLC and sarcoma, with all patients receiving ≥1 dose of GSK’227. At baseline, 47.2% of patients enrolled in the trial received ≥3 prior lines therapy with a mean of 3.2 lines of prior therapy. The maximum tolerated dose was 12 mg/kg. A partial response rate was observed in 35% of patients treated with GSK’227, while the disease control rate was 85%. At the time of publication, the patient with the longest treatment duration was still being treated, with 349 days being reported.

Common treatment-emergent adverse events (TEAEs) included leukopenia, neutropenia, anemia, pyrexia, nausea, thrombocytopenia, hypoalbuminemia, vomiting, lymphopenia, infusion-related reaction and fatigue, with no interstitial lung disease reported. Study investigators found that the safety profile of GSK’227 was acceptable. Additionally, it demonstrated promising antitumor activity in several tumor types, especially in SCLC. The expansion study on the safety and efficiacy of the treatment is currently in progress.²

Of the 15% of lung cancer patients who have SCLC, around 70% have ES-SCLC, resulting in the cancer spreading throughout one or both lungs and/or to other parts of the body. The current five-year survival rate for patients with ES-SCLC is 3%, with many patients relapsing after initial treatment. The median overall survival with current standard-of-care treatments is five to six months.1 According to the American Cancer Society, two out of three people with SCLC have extensive disease when their cancer is first found.³

References

1. 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. GSK. August 20, 2024. Accessed August 21, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-us-fda-breakthrough-therapy-designation/

2. Small Cell Lung Cancer Stages. American Cancer Society. Accessed August 21, 2024. https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/staging-sclc.html#:~:text=is%20first%20found.-,Extensive%20stage,their%20cancer%20is%20first%20found.

3. ARTEMIS-001: Phase 1 study of HS-20093, a B7-H3–targeting antibody-drug conjugate, in patients with advanced solid tumor. ASCO. Accessed August 21, 2024. https://meetings.asco.org/abstracts-presentations/226559