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A Type II variation application has been submitted to the European Medicines Agency (EMA) seeking expanded approval of sugemalimab (Cejemly) for the treatment of patients with unresectable stage III non–small cell lung cancer (NSCLC) who have not progressed following concurrent or sequential platinum-based chemoradiotherapy.1
Sugemalimab is a fully human, full-length anti–PD-L1 IgG4 monoclonal antibody that minimizes immunogenicity and toxicity.
The application is supported by data from the phase 3 GEMSTONE-301 trial (NCT03728556), which evaluated sugemalimab as consolidation therapy in this population. Results published in The Lancet Oncology in 2022 demonstrated a 36% reduction in the risk of disease progression or death and a 56% reduction in the risk of death with sugemalimab vs placebo, with consistent benefits observed across patient subgroups and a favorable safety profile.1,2
This Type II variation application follows the prior EMA approval of sugemalimab plus platinum-based chemotherapy in 2024 for the treatment of adult patients with metastatic NSCLC that does not harbor EGFR mutations or ALK, ROS1, or RET genomic alterations.3 If the indication for sugemalimab is expanded to include patients with stage III NSCLC, the agent would become the second PD-L1 inhibitor available in Europe for patients in this population.1
“Following sugemalimab’s approval in Europe for stage IV NSCLC, we are working closely with the EMA to expand [this agent’s] indications in earlier-stage lung cancer and other malignancies,” Jason Yang, MD, PhD, chief executive officer, president of R&D, and executive director at CStone, stated in a news release. “With its demonstrated outstanding efficacy and safety profile, sugemalimab is poised to address critical unmet needs for [patients with] stage III NSCLC.”
GEMSTONE-301 Trial Design and Enrollment Criteria
GEMSTONE-301 was a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of sugemalimab as consolidation therapy in patients with unresectable, stage III NSCLC who had not experienced disease progression following concurrent or sequential platinum-based chemoradiotherapy.4 The trial was conducted across 50 hospitals and academic research centers in China.2
Patients were required to have histologically confirmed, locally advanced, unresectable stage III NSCLC and be at least 18 years of age at the time of informed consent.4 Additional eligibility criteria included completion of platinum-based concurrent or sequential chemoradiotherapy without disease progression, an ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks.
Additionally, patients were required to initiate treatment with sugemalimab within 1 to 42 days following chemoradiotherapy completion and demonstrate adequate organ function based on laboratory assessments. All prior anticancer therapy–related toxicities—excluding alopecia, fatigue, and hearing loss—were required to resolve to grade 1 or baseline. Women of childbearing potential and fertile men were required to use effective contraception throughout the study and for 180 days following the last dose of study drug.
Patients with histologically confirmed mixed small cell lung cancer or evidence of disease progression following chemoradiotherapy were excluded. Additional key exclusion criteria included prior major surgery within 28 days of first study dose, receipt of live vaccines within 28 days of first study dose, or concurrent enrollment in another interventional clinical trial.
Patients with prior exposure to immune checkpoint inhibitors, active autoimmune disease, or ongoing exposure to systemic immunosuppression were also excluded. Other exclusions encompassed active infections including HIV, hepatitis B, or hepatitis C; a known additional malignancy within 5 years; history of inflammatory bowel disease; prior organ transplantation; severe allergic reactions to monoclonal antibodies; uncontrolled substance use; or QTc prolongation.
Patients were randomly assigned in a 2:1 ratio to receive intravenous sugemalimab at 1200 mg or matching placebo every 3 weeks for up to 24 months.2 Randomization was stratified by ECOG performance status (0 vs 1), type of prior chemoradiotherapy (concurrent vs sequential), and total radiotherapy dose received. Treatment allocation was masked for investigators, site personnel, patients, and the sponsor.
The primary end point of the study was progression-free survival, as assessed by blinded independent central review. Safety assessments were conducted in all patients who received at least 1 dose of the assigned treatment.
References
CStone submits application to the European Medicines Agency for new indication of sugemalimab in stage III non-small cell lung cancer. CStone Pharmaceuticals. Published March 24, 2025. Accessed March 24, 2025. https://www.cstonepharma.com/en/html/news/3787.html
Zhou Q, Chen M, Jiang O, et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. The Lancet Oncology. 2022;23(2):209-219. doi:10.1016/s1470-2045(21)00630-6
CStone announces European Commission approval of sugemalimab (Cejemly) as first-line treatment for non-small cell lung cancer. March 24, 2025. https://www.cstonepharma.com/en/html/news/3717.html
A study of CS1001 in subjects with stage III non-small cell lung cancer. ClinicalTrials.gov. Updated June 15, 2023. Accessed March 24, 2025. https://clinicaltrials.gov/study/NCT03728556