FDA Grants B7-H3–Targeted ADC Breakthrough Status in Osteosarcoma

• The FDA has granted breakthrough therapy designation (BTD) to GSK5764227 (GSK’227) for the treatment of adult patients with relapsed or refractory osteosarcoma who have progressed after at least 2 prior lines of therapy.
• GSK’227 is a B7-H3-targeted antibody-drug conjugate (ADC).
• This designation is intended to expedite the development and review of therapies that show early promise in addressing serious or life-threatening conditions with limited treatment options.

The FDA has granted BTD to GSK’227, a B7-H3-targeted ADC being evaluated for the treatment of adult patients with relapsed/refractory osteosarcoma who have progressed on at least 2 prior lines of therapy.¹

This FDA decision was supported by data from the phase 2, open-label, randomized, multicenter ARTEMIS-002 study (NCT05830123) evaluating the efficacy and safety of GSK’227 in patients with relapsed/refractory osteosarcoma and other sarcomas. The trial enrolled over 60 patients, including 42 with osteosarcoma.

Preliminary results, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated promising antitumor activity and a manageable safety profile for GSK’227 in this difficult-to-treat patient population.

GSK’227 is a novel ADC that combines a fully human anti-B7-H3 monoclonal antibody with a topoisomerase inhibitor payload. The B7-H3 protein, widely expressed on tumor cells and minimally present in normal tissues, represents an attractive therapeutic target. Preclinical and early clinical data suggest that GSK’227 may offer significant efficacy while minimizing off-target effects.¹

This is the third regulatory designation for GSK’227, following the European Medicines Agency’s decision to grant priority medicines (PRIME) designation and the FDA’s decision to grant BTD for the treatment of patients with relapsed/refractory extensive-stage small-cell lung cancer in August 2024 and December 2024, respectively. Also in August 2024, GSK, the drug developer, initiated a global phase 1 trial (NCT06551142) to further evaluate the safety and efficacy of GSK’227 across multiple indications. This trial is part of a comprehensive development plan aimed at securing regulatory approval for the ADC.

About the ARTEMIS-002 Study

The ARTEMIS-002 study is evaluating the efficacy, safety, pharmacokinetics (PK), and immunogenicity of GSK’227 when used as a monotherapy for the treatment of patients with relapsed/refractory osteosarcoma and other sarcomas.² ARTEMIS-002 is a phase 2, open-label, multicenter trial which consists of 2 parts: phase 2a and 2b.

The first phase of the trial, phase 2a, includes cohort 1, which will consist of patients with advanced osteosarcoma upon disease progression after standard treatment, and cohort 2, which includes those with other unresectable bone and soft tissue sarcomas, if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. Once enrolled, patients will be randomly assigned 1:1 to receive the agent at a dose of 8.0 mg/kg and 12.0 mg/kg in cohort 1 and 12.0 mg/kg in cohort 2.

For phase 2b, patients with advanced osteosarcoma upon disease progression after standard treatment will be enrolled. Patients will receive GSK’227 at the recommended dose from phase 2a.

Investigators will carefully follow all patients for adverse events (AEs) during the study treatment and for 90 days after the last dose of the agent. Patients are allowed to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists.

Additional enrollment criteria for the study include having histologically confirmed relapsed or refractory osteosarcoma or other sarcomas that have progressed upon first-line systemic treatment and 1 or more measurable lesions according to RECIST 1.1. Patients must agree to provide fresh or archival tumor tissue and peripheral blood samples, have an ECOG performance score of 0 or 1, a life expectancy of at least 12 weeks, and be using adequate contraceptive measures throughout the duration of the study.

The primary end point of the study is overall response rate and secondary end points are incidence and severity of AEs, PK, duration of response, disease control rate, progression-free survival (PFS), overall survival, and 4-month PFS rate determined by investigators and independent review committee according to RECIST 1.1.

REFERENCES

1. GSK’s B7-H3-targeted antibody-drug conjugate, GSK’227, receives US FDA breakthrough therapy designation in late-line relapsed or refractory osteosarcoma. News release. GSK plc. January 7, 2025. Accessed January 7, 2025. https://tinyurl.com/bd2u6px7

2. ARTEMIS-002: HS-20093 in patients with relapsed or refractory osteosarcoma and other sarcomas. ClinicalTrials.gov. Updated August 23, 2024. Accessed January 7, 2025. https://www.clinicaltrials.gov/study/NCT05830123?tab=table