First-Line Sugemalimab Plus Chemo Wins European Approval for Metastatic NSCLC

The European Commission has approved sugemalimab (Cejemly) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with metastatic non–small cell lung cancer (NSCLC) that does not harbor sensitizing EGFR mutations, or ALK, ROS1, or RET genomic aberrations.¹

The regulatory decision was supported by data from the phase 3 GEMSTONE-302 trial (NCT03789604), which showed that sugemalimab plus chemotherapy reduced the risk of disease progression or death by 52% compared with placebo plus chemotherapy (stratified HR, 0.48; 95% CI, 0.39-0.60; P < .0001). Data from the final analysis showed that, at a median follow-up of 17.8 months (interquartile range, 15.1-20.9), patients treated with sugemalimab plus chemotherapy (n = 320) experienced a median progression-free survival (PFS) of 9.0 months (95% CI, 7.4-10.8) vs 4.9 months (95% CI, 4.8-5.1) for those treated with placebo plus chemotherapy (n = 159).²

“We are extremely excited by today’s announcement, which represents a major milestone in CStone’s journey towards becoming a leading global company dedicated to eradicating cancer. Sugemalimab has not only become CStone's first independently developed product to receive overseas marketing authorization but it is also the world's first anti–PD-L1 monoclonal antibody to receive regulatory approval in Europe in combination with chemotherapy as first-line treatment for both squamous and nonsquamous NSCLC,” Jason Yang, MD, PhD, chief executive officer, president of R&D, and executive director of the Board at CStone Pharmaceuticals, stated in a news release.1

“This achievement reflects the international regulatory authorities' recognition of our high-quality R&D and manufacturing standards, and it infuses new momentum into our globalization strategy,” he continued. “We are humbled by level of interest in sugemalimab commercial partnership from companies around the world which only signifies the large unmet need in this class for newer and better drugs. We are actively engaging with potential partners in Western Europe, Latin America, the Middle East and Africa, Southeast Asia, and Canada and we expect to announce the completion of these deals soon."

The double-blind GEMSTONE-302 trial, which was conducted at 35 hospitals and research centers in China, enrolled patients between 18 and 75 years of age with histologically or cytologically confirmed stage IV squamous or nonsquamous NSCLC that did not harbor EGFR sensitizing mutations, or ALK, ROS1, or RET fusions. No prior systemic treatment for metastatic disease was allowed. An ECOG performance status of 0 or 1 was required.²

Patients were randomly assigned 2:1 to receive 1200 mg of sugemalimab intravenously once every 3 weeks or matching placebo in chemotherapy. Patients with squamous NSCLC received carboplatin at area under the curve (AUC) 5 mg/mL and paclitaxel at 175 mg/m2; those with nonsquamous disease received carboplatin at AUC 5 mg/mL plus pemetrexed 500 mg/m2 for up to 4 cycles. After the completion of chemotherapy, patients with squamous disease received sugemalimab or matching placebo as maintenance; those with nonsquamous NSCLC received sugemalimab plus pemetrexed or placebo plus pemetrexed as maintenance. Sugemalimab or placebo were given for up to 35 cycles, or until disease progression or unacceptable toxicity.

Investigator-assessed PFS in the intention-to-treat population was the trial’s primary end point.

Data were immature to conduction the final analysis for overall survival (OS). A preliminary analysis of OS showed that the median OS was 22.8 months (95% CI, 19.7–not reached) for the sugemalimab arm vs 17.7 months (95% CI, 12.8-20.8) for the placebo arm (stratified HR, 0.67; 95% CI, 0.50-0.90; P = .0064). The 12- and 24-month OS rates for the sugemalimab arm were 72.4% (95% CI, 67.0%-77.0%) and 47.1% (95% CI, 37.2%-56.4%), respectively. These respective rates were 62.0% (95% CI, 53.6%-69.3%) and 38.1% (95% CI, 27.2%-49.0%).

Regarding safety, the most common grade 3/4 treatment-related adverse effects (TRAEs) included decreased neutrophil count decreased (sugemalimab, 33%; placebo, 33%), decreased white blood cell count (14%; 17%), anemia (13%; 11%), decreased platelet count (10%; 9%), and neutropenia (4%; 4%). Any-grade serious TRAEs were reported in 23% of patients in the sugemalimab arm and 20% of patients in the placebo arm A.

Any treatment-related deaths occurred in 3% of patients in the sugemalimab group, which included causes of pneumonia with respiratory failure (n = 1), myelosuppression with septic shock (n = 1), pneumonia (n = 2), respiratory failure (n = 1), abdominal pain (n = 1), cardiac failure (n = 1), immune-mediated pneumonitis (n = 1) and unspecified cause (n = 2). TRAEs led to death in 1% of patients in the placebo group, which were comprised of once instance each of pneumonia and multiple organ dysfunction syndrome.

References

1. CStone announces European Commission approval of sugemalimab (Cejemly) as first-line treatment for non-small cell lung cancer. News release. CStone Pharmaceuticals. July 26, 2024. Accessed July 26, 2024. https://www.cstonepharma.com/en/html/news/3717.html
2. Zhou C, Wang Z, Sun Y, et al. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol. 2022;23(2):220-233. doi:10.1016/S1470-2045(21)00650-1