Sugemalimab Plus Chemo Receives Approval in China for Esophageal Squamous Cell Carcinoma

The National Medical Products Administration of China has approved sugemalimab paired with fluorouracil and platinum-based chemotherapy for use in the frontline treatment of patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma.

The National Medical Products Administration of China has approved sugemalimab (Cejemly) paired with fluorouracil and platinum-based chemotherapy for use in the frontline treatment of patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).1

The regulatory decision was supported by data from the phase 3 GEMSTONE-304 study (NCT04187352), in which the combination significantly improved progression-free survival (PFS) and overall survival (OS) by blinded independent central review (BICR) assessment vs chemotherapy alone in this population, meeting the prespecified primary end points of the trial.2

The median BICR-assessed PFS achieved with sugemalimab plus chemotherapy was 6.2 months vs 5.4 months with chemotherapy alone, translating to a 33% reduction in the risk of disease progression or death (HR, 0.67; 95% CI, 0.54-0.82; P = .0002). The median OS with the sugemalimab combination was 15.3 months vs 11.5 months with chemotherapy alone, which translates to a 30% reduction in the risk of death (HR, 0.70; 95% CI, 0.55-0.90; P = .0076).

“The GEMSTONE-304 study demonstrated that sugemalimab in combination with chemotherapy significantly improved PFS and OS compared to first-line chemotherapy for ESCC, with a manageable safety profile,” Professor Li Jin, principal investigator of the study and the director of the Department of Oncology at East Hospital, Tongji University, stated in a press release.1 “We believe, with this approval, sugemalimab will provide a new first-line treatment option to patients with advanced ESCC.”

The double-blind, multicenter, placebo-controlled phase 3 study enrolled patients with histologically or cytologically confirmed unresectable locally advanced, relapsed, or metastatic ESCC who were at least 18 years of age but no older than 75 years.3 Patients could not be eligible to undergo radical therapy. They needed to have an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and at least 1 measurable lesion.

Patients with adenocarcinoma, a mix of adenocarcinoma and squamous cell carcinoma, or another type of esophageal cancer, were excluded. Other exclusion criteria included: active central nervous system metastasis, another active primary malignancy in the past 5 years except local curable cancers that have received curative treatment, and a known history of positive human immunodeficiency, among others.

Study participants received placebo or sugemalimab at 1200 mg every 3 weeks plus fluorouracil at 800 mg/m2 daily on days 1 to 4 of each cycle and cisplatin at 80 mg/m2 on the first day of each cycle.

Key secondary end points included investigator-assessed PFS, BICR-assessed objective response rate (ORR), and BICR-assessed duration of response (DOR)—all according to RECIST v1.1 criteria.

Additional data showed that sugemalimab plus chemotherapy elicited an ORR of 60.1% vs 45.2% with chemotherapy alone, translating to a percentage difference of 14.9% (95% CI, 5.9%-23.8% (P = .0011).2 The DOR in the sugemalimab arm was 6.0 months vs 4.5 months in the placebo arm.

Moreover, findings from a subgroup analysis indicated that sugemalimab plus chemotherapy produced clinical benefits spanning all predefined subsets, including PD-L1 expression status.

The sugemalimab combination demonstrated an acceptable toxicity profile and favorable tolerability. No new safety signals were observed.

References

  1. CStone announces NMPA approval of sugemalimab as first-line treatment for esophageal squamous cell carcinoma. News release. CStone Pharmaceuticals. December 8, 2023. Accessed December 20, 2023. https://www.cstonepharma.com/en/html/news/3644.html#:~:text=Sugemalimab%20becomes%20the%20world's%20first,its%20clinical%20significance%20and%20potential.
  2. CStone presents results from phase 3 study of sugemalimab in first-line esophageal squamous cell carcinoma at ESMO GI 2023. News release. CStone Pharmaceuticals. June 30, 2023. Accessed December 20, 2023. https://www.cstonepharma.com/en/html/news/2940.html
  3. A study of CS1001 in subjects with esophageal squamous cell carcinoma. ClinicalTrials.gov. Updated November 24, 2023. Accessed December 20, 2023. https://clinicaltrials.gov/study/NCT04187352