Sugemalimab Plus Chemotherapy Earns UK Approval in First-Line Metastatic NSCLC

The United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency has approved sugemalimab (Cejemly) plus 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.¹

In June 2024, sugemalimab plus chemotherapy was approved by the European Commission for the same indication², making this regulatory decision the second international marketing authorization for sugemalimab outside of China.¹

Findings from the multicenter, randomized, double-blind phase 3 GEMSTONE-302 trial (NCT03789604), which have been published in both The Lancet Oncology and Nature Cancer, supported this approval. Updated data presented at the 2024 ESMO Congress demonstrated that after approximately 4 years of follow-up, sugemalimab plus chemotherapy maintained significant progression-free survival (PFS) and overall survival (OS) benefit vs placebo plus chemotherapy.

As of the data cutoff on May 15, 2023, patients in the intention-to-treat (ITT) population treated with the sugemalimab regimen (n = 320) achieved a median OS of 25.2 months (95% CI, 20.1-30.2) vs 16.9 months (95% CI, 12.8-20.7) for those treated with placebo (n = 159; HR, 0.68; 95% CI, 0.54-0.85). 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).³

Notably, survival benefit with sugemalimab plus chemotherapy was consistent across different histological subtypes and PD-L1 expression levels.^3,4

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+). The 4-year OS rate for this patient population was 92.6%. PFS (HR, 0.31; 95% CI, 0.17-0.58) and OS (HR, 0.44; 95% CI, 0.24-0.81) were also prolonged in patients with baseline brain metastases. The median OS within this subgroup was 26.0 months vs 9.0 months with sugemalimab vs placebo, respectively (HR, 0.72; 95% CI, 0.53-0.98). The 4-year OS rate with sugemalimab plus chemotherapy was 36.4%.

Regarding safety, the regimen exhibited a manageable toxicity profile, with no new safety signals identified.³

"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,” Jason Yang, MD, PhD, chief executive officer, president of Research and Development, and executive director of the board at CStone, stated in a news release.1 “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 Overview

GEMSTONE-302 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, orALK, 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.³

Upon enrollment, patients were randomly assigned 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 study’s primary end point was investigator-assessed PFS. Key secondary end points 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), DOR, and safety.

Current and Potential Indications for Sugemalimab

In addition to its European approvals, sugemalimab is approved by China’s National Medical Products Administration for the following 5 indications:¹

• In combination with chemotherapy as first-line treatment of patients with metastatic squamous and non-squamous NSCLC.
• For patients with unresectable stage III NSCLC whose have not experienced disease progression after concurrent or sequential platinum-based chemoradiotherapy.
• For patients with relapsed or refractory extranodal NK/T-cell lymphoma.
• In combination with fluorouracil and platinum-based chemotherapy as a first-line treatment in unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).
• In combination with fluoropyrimidine- and platinum-containing chemotherapy as 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.
• Discussions with regulatory authorities European Medicines Agency are underway to expand marketing authorization for additional indications of sugemalimab.

Yang noted that "We are actively pursuing additional partnerships across Western Europe, Latin America, the Middle East, Southeast Asia, and Canada, and expect to finalize some of these agreements shortly. Meanwhile, we are communicating with the EMA and other agencies for additional regulatory applications for other sugemalimab indications, including stage III NSCLC, first-line gastric cancer, and first-line ESCC, aiming to bring innovative treatment options to more patients globally."

References

1. CStone announces MHRA approval of sugemalimab for first-line treatment of non-small cell lung cancer (NSCLC) in the UK. News Release. CStone. October 31, 2024. Accessed October 31, 2024. https://www.cstonepharma.com/en/html/news/3747.html
2. 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 October 31, 2024. https://www.cstonepharma.com/en/html/news/3717.html
3. Zhou C, Wang Z, Sun Y, et al. Four-year outcomes from GEMSTONE-302 study: First-line sugemalimab plus platinum-based chemotherapy in metastatic non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35(suppl 2): S802-S877. 10.1016/annonc/annonc1602
4. CStone announces long-term survival data for sugemalimab (Cejemly®) in combination with platinum-based chemotherapy as first-line treatment of stage IV NSCLC at ESMO 2024. News Release. CStone. September 14, 2024. Accessed October 31, 2024. https://www.cstonepharma.com/en/html/news/3730.html