FDA Grants Breakthrough Therapy Designation to GSK’227 in ES-SCLC

Supporting data for the designation comes from the ARTEMIS-001 trial evaluating preliminary safety and antitumor activity of GSK’227 in solid tumors.

The FDA has granted the B7-H3–targeted antibody drug conjugate (ADC) GSK5764227 (GSK’227, HS-20093) breakthrough therapy designation as a treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), according to a news release from the drug’s developer, GSK.¹

The FDA’s decision is supported by data published on the phase 1 ARTEMIS-001 trial (NCT05276609) evaluating preliminary safety and antitumor activity of GSK’227 in patients with relapsed ES-SCLC. Results from the trial were presented at 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Data showed tumor shrinkage occurring in 96.2% (n = 50/52) of patients with evaluable targeted lesions.² Additionally, tumor shrinkage of 50% or more, or deep responses, occurred in 44.2% of patients. Median overall survival (OS) was not reached, and responses were reported regardless of B7-H3 expression.

“[ES-SCLC] is aggressive with poor prognosis and significant need for new treatments,” Hesham Abdullah, senior vice president and global head of Oncology Research and Development at GSK, said in the news release.¹ “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.”

Investigators of the trial enrolled 56 patients with ES-SCLC as of the data cutoff date of November 30, 2023. Patients were disaggregated into 2 arms and received at least 1 dose of GSK’227: 31 received 8.0 mg/kg, and 25 received 10.0 mg/kg once every 3 weeks. Before treatment, platinum-based therapy plus etoposide and immunotherapy were administered to 100% (n = 56/56) and 73.2% (n = 41/56) patients, respectively. There were 2 median lines of therapy across cohorts (range, 1-6).

Primary end points include maximum tolerated dose for GSK’227 in phase 1a and objective response rate (ORR) in phase 1b.³ Secondary end points include adverse effects (AEs), maximum plasma concentration and time to reach maximum plasma concentration, terminal half-life, duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS), among others.

At a median follow-up time of 4.8 (95% CI, 3.6-5.6) and 4.9 (95% CI, 4.1-5.6) months, ORR for the 8.0 mg/kg and 10.0 mg/kg arms were 58.1% (95% CI, 39.1%-75.5%) and 57.1% (95% CI, 34.0%-78.2%). DCR was 80.6% (95% CI, 62.5%-92.5%) and 95.2% (95% CI, 76.2%-99.9%). Median DOR and PFS was 4.3 months (95% CI, 3.3-not available [NA]) and 5.6 months (95% CI, 3.4-NA) in the 8.0 mg/kg arm and not reached for either (95% CI, 3.1-NA; 95% CI, 4.4-NA) in the 10.0 mg/kg arm.

Approximate dose-proportional increases in exposure were observed for the pharmacokinetic (PK) profile, with a half-life of 3 to 7 days. Total antibody and ADC PK profiles were similar with low exposure to payload observed.

The safety profile was consistent with previous reports, with the most common grade 3 or greater treatment-related AEs occurring in 10% of more patients including neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.

Inclusion criteria include adult patients with ES-SCLC with histologically or cytologically confirmed locally advanced or metastatic solid tumors not amenable to standard treatment, at least 1 extra-cranial measurable lesion, an ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks from baseline.

Key exclusion criteria include prior treatment with B7-H3 targeted therapy or a cytotoxic chemotherapy, investigational agent, or anticancer drug within 14 days prior to first dose, or a monoclonal antibody within 28 days prior to first dose, among other treatments.

A phase 3 study comparing efficacy and safety of GSK’227 vs standard-of-care chemotherapy in relapsed SCLC is planned.

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. News release. GSK. August 20, 2024. Accessed August 20, 2024. https://tinyurl.com/4e2yecs7
2. Wang J, Duan J, Sun Y, et al. ARTEMIS-001: data from a phase 1a/b study of HS-20093 in patients with relapsed small cell lung cancer (SCLC). J Clin Oncol. 2024;42(suppl 16):8093. doi:10.1200/JCO.2024.42.16_suppl.8093
3. ARTEMIS-001: phase 1 Study of the HS-20093 in patients with advanced solid tumors. ClinicalTrials.gov. Updated February 15, 2023. Accessed August 20, 2024. https://www.clinicaltrials.gov/study/NCT05276609