GSK5764227 Gains FDA Breakthrough Therapy Designation in ES-SCLC

• The FDA has granted breakthrough therapy designation (BTD) to GSK5764227 (GSK’227; HS-20093) in extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
• GSK’227 is an investigational B7-H3-targeted antibody-drug conjugate (ADC).
• The BTD is designed to accelerate the development and review process for drugs that have the potential to treat serious conditions, especially when early clinical evidence suggests they may offer significant improvements over existing therapies.

A BTD has been granted to GSK’227, an investigational B7-H3-targeted ADC, by the FDA for the treatment of patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.¹

Data from the ongoing phase 1 ARTEMIS-001 trial (NCT05276609) support this BTD. In this study, over 200 patients with locally advanced or metastatic solid tumors, including relapsed/refractory ES-SCLC, are being enrolled to determine the safety, tolerability, and preliminary antitumor activity of GSK’227.

The findings from this study will be presented at the World Conference on Lung Cancer on September 7 to 10, 2024. In addition, global phase 1/2 trials of GSK’227 are expected to begin in the second half of 2024 to support a registrational pathway for the agent.

“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, senior vice president, global head of oncology research and development at GSK, in a press release.

Small cell lung cancer: © Констянтин Батыльчук- stock.adobe.com

ARTEMIS-001 is an open-label, multicenter, dose-escalation, and dose-expansion study where investigators are evaluating the safety, tolerability, pharmacokinetics (PKs), and the therapeutic potential of GSK’227 when used alone for the treatment of patients with advanced solid tumors.²

In part 1a of the study, patients with advanced cancer are eligible if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. This dose-escalation portion of the trial will include an initial accelerated titration design followed by a 3+3 design. Part 1b plans to enroll patients into the dose-expansion portion following the identification of the maximum tolerated dose (MTD) in phase 1a. The dose-expansion study will include patients with locally advanced or metastatic non–small cell lung cancer, ES-SCLC, and other types of advanced solid tumors.

Patients will continue to be followed for adverse events (AEs) during the study treatment and for 90 days after the last dose of study drug. Further, patients can continue therapy with assessments for progression if the product is well tolerated and if they have a sustained clinical benefit.

Enrollment is open to patients aged at least 18 years at screening with histologically or cytologically confirmed, locally advanced or metastatic solid tumors for which standard treatment either does not exist or has proven ineffective, unavailable, or intolerable. Patents must have at least 1 extracranial measurable lesion, agree to provide fresh or archival tumor tissue, have an ECOG performance status of 0 or 1, and have a life expectancy of at least 12 weeks.

The primary end point for part 1a is to determine the MTD of the agent, and the primary end point for part 1b is objective response rate (ORR) according to RECIST v1.1. Secondary end points for both parts include incidence and severity of AEs, PKs, ORR, duration of response, disease control rate, progression-free survival, and overall survival.

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 plc. August 20, 2024. Accessed August 20, 2024. https://tinyurl.com/mwhjzhhn

2. ARTEMIS-001: Phase 1 study of the HS-20093 in patients with advanced solid tumors. ClinicalTrials.gov. Updated February 15, 2024. Accessed August 20, 2024. https://clinicaltrials.gov/study/NCT05276609