Sugemalimab Plus Chemo Receives Approval in China for 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