The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted approval to sugemalimab (Cejemly) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) who do not harbor sensitizing EGFR mutations or ALK, ROS1, RET alterations. This decision marks the second international marketing authorization for sugemalimab outside of China, following its approval by the European Commission in June 2024 for the same indication. The approval is based on data from the phase 3 GEMSTONE-302 trial, demonstrating significant improvements in progression-free survival (PFS) and overall survival (OS).
GEMSTONE-302 Trial Results
The multicenter, randomized, double-blind phase 3 GEMSTONE-302 trial (NCT03789604) evaluated the efficacy and safety of sugemalimab plus chemotherapy versus placebo plus chemotherapy in patients with metastatic NSCLC. Updated data presented at the 2024 ESMO Congress, with approximately 4 years of follow-up, confirmed the sustained benefits of the sugemalimab regimen.
As of the data cutoff on May 15, 2023, patients in the intention-to-treat (ITT) population who received sugemalimab plus chemotherapy (n = 320) achieved a median OS of 25.2 months (95% CI, 20.1-30.2) compared to 16.9 months (95% CI, 12.8-20.7) for those treated with placebo plus chemotherapy (n = 159; HR, 0.68; 95% CI, 0.54-0.85). The four-year OS rates were 32.1% and 17.3%, respectively. The median PFS in the ITT population was 9.0 months (95% CI, 7.4-10.9) with sugemalimab and 4.9 months (95% CI, 4.8-5.2) with placebo (HR, 0.49; 95% CI, 0.39-0.60; P < .0001).
Notably, the survival benefit with sugemalimab plus chemotherapy was consistent across different histological subtypes and PD-L1 expression levels.
Long-Term Outcomes and Safety
Among patients who received sugemalimab for over 2 years (n = 58) at the data cutoff, the median duration of response was not reached (range, 31.4+-50.2+), and the 4-year OS rate for this patient population was 92.6%. In patients with baseline brain metastases, PFS (HR, 0.31; 95% CI, 0.17-0.58) and OS (HR, 0.44; 95% CI, 0.24-0.81) were also prolonged. The median OS within this subgroup was 26.0 months versus 9.0 months with sugemalimab versus placebo, respectively (HR, 0.72; 95% CI, 0.53-0.98), and the 4-year OS rate with sugemalimab plus chemotherapy was 36.4%.
The regimen demonstrated a manageable toxicity profile, with no new safety signals identified.
CStone's Perspective
"This approval is a significant milestone in our global expansion strategy. Sugemalimab is the first domestic anti–PD-L1 antibody to receive approval outside of China and has already entered the world's second-largest pharmaceutical market, the European Union,” said Jason Yang, MD, PhD, chief executive officer, president of Research and Development, and executive director of the board at CStone. “Now, with the UK approval, sugemalimab continues to expand its presence in the European market. The long-term survival data, recently presented at this year's ESMO Congress, further confirmed sugemalimab's value in the frontline treatment landscape for metastatic NSCLC."
GEMSTONE-302 Trial Design
The GEMSTONE-302 trial enrolled patients aged 18 to 75 years with histologically or cytologically confirmed stage IV squamous or nonsquamous NSCLC without EGFR sensitizing mutations or ALK, ROS1, or RET fusions. Patients were required to have no prior chemotherapy exposure, measurable disease, an ECOG performance status of 0 or 1, and tumor tissue available for PD-L1 expression testing.
Patients were randomized 2:1 to receive 1200 mg of sugemalimab intravenously (IV) once every 3 weeks or placebo plus chemotherapy as induction. Following completion of chemotherapy, patients with squamous disease received sugemalimab or placebo as maintenance for up to 35 cycles; 500 mg/m2 of IV pemetrexed was added to both regimens for patients with nonsquamous NSCLC. Crossover to the investigational arm to receive sugemalimab was permitted in the event of disease progression.
The primary endpoint of the study was investigator-assessed PFS. Key secondary endpoints included OS, PFS assessed by blinded independent central review (BICR), PFS in patients with PD-L1 expression ≥1% as assessed by investigators, objective response rate (ORR), duration of response (DOR), and safety.
Sugemalimab's Existing and Potential Indications
Sugemalimab is also approved in China for several indications, including first-line treatment of metastatic squamous and non-squamous NSCLC in combination with chemotherapy, unresectable stage III NSCLC after chemoradiotherapy, relapsed or refractory extranodal NK/T-cell lymphoma, first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), and first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with a PD-L1 combined positive score of 5 or greater.
CStone is actively pursuing additional partnerships and communicating with the EMA and other agencies for further regulatory applications for sugemalimab in other indications, including stage III NSCLC, first-line gastric cancer, and first-line ESCC.
