Surufatinib Plus Serplulimab and Chemo Shows Activity in First-Line Extrapulmonary NEC

Surufatinib combined with serplulimab and etoposide/cisplatin (EP) demonstrated encouraging antitumor activity as first-line treatment of patients with advanced or metastatic extrapulmonary neuroendocrine carcinoma (NEC), according to updated findings from a phase 1/2 trial (NCT05747729) presented at the 2026 ESMO Congress.¹

Findings showed that as of the May 30, 2026, data cutoff, response-evaluable patients (n = 43) achieved a confirmed objective response rate (ORR) of 69.8%, a disease control rate (DCR) of 95.3%, and a median duration of response of 9.1 months. Median progression-free survival (PFS) was 9.4 months (95% CI, 6.6-13.9) in evaluable patients (n = 46).¹

“[Trial] enrollment is still ongoing, and mature survival data are awaited,” lead study author Zhenyu Yu Lin, MD, of the Cancer Center and Institute of Radiation Oncology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, in Wuhan, China, said in a presentation of the data.“

What is the mechanism of action of the combination?

Surufatinib is an oral multi-kinase inhibitor targeting VEGFR-1, VEGFR-2, VEGFR-3, FGFR-1, and CSF-1R, providing an antiangiogenic and immunomodulatory rationale for combination treatment. Serplulimab is a humanized anti–PD-1 monoclonal antibody. The regimen combines these targeted and immune-directed approaches with the EP chemotherapy backbone.

How is the study being conducted?

Eligible patients needed to be at least 18 years old with previously untreated, histologically confirmed extrapulmonary NEC.^1,2 Measurable disease and an ECOG performance status of 0 or 1 were also required. The protocol also permitted mixed neoplasms containing at least a 30% NEC component, and patients required adequate organ function and an expected survival exceeding 3 months.²

Patients were excluded if they had pulmonary NEC, symptomatic brain metastases, uncontrolled hypertension, active bleeding, significant uncontrolled cardiac disease, or active autoimmune disease requiring systemic treatment.

The study included a 6-patient safety run-in, followed by a 54-patient dose-expansion cohort.¹ During the run-in, patients received surufatinib at a starting dose of 250 mg orally once daily, serplulimab at 300 mg intravenously on day 1 every 3 weeks, and EP. Etoposide was administered at 100 mg/m² intravenously on days 1 through 3, with cisplatin at 25 mg/m² intravenously on days 1 through 3 of each 21-day cycle. Induction treatment continued for up to 6 cycles, followed by maintenance surufatinib plus serplulimab until disease progression, death, or intolerable toxicity.

Dose-limiting toxicities were monitored during the first cycle. The protocol specified reducing surufatinib to 200 mg daily if at least 2 of the first 6 patients experienced dose-limiting toxicities. Dose expansion used the recommended phase 2 dose determined during the run-in. Tumors were assessed every 6 weeks using RECIST 1.1 criteria.

The primary end point was PFS assessed using RECIST 1.1 criteria. Secondary end points included ORR, DCR, DOR, overall survival, and adverse effects (AEs).

Of 56 screened patients, 53 enrolled and received treatment. Seven had not yet reached tumor assessment, leaving 46 assessed for PFS and safety. Three additional patients were not evaluable for response, resulting in a 43-patient response-evaluable population.

At baseline (n = 46), the median was 60 years (range, 32–77); 67.4% were younger than 65 years of age, and 32.6% were at least 65 years of age. Most were men (63.0%), and ECOG performance status was 0 in 21.7% and 1 in 78.3%.

The most common primary tumor sites were intestine (32.6%), stomach (21.7%), and pancreas (17.4%). Esophageal and biliary tract primaries each accounted for 6.5%, uterine primaries for 4.3%, other sites for 6.5%, and an unknown primary for 4.3%. Liver metastases were present in 67.4% of patients. The median Ki-67 index was 70% (range, 30%-90%), with 78.3% having a Ki-67 index of at least 55%. Previous surgery was reported in 23.9%.

What additional efficacy findings were reported?

Among the response-evaluable population, 1 achieved a complete response and 29 experienced partial responses. Stable disease occurred in 11 patients, and 2 had a best response of progressive disease.

Responders experienced a median PFS of 11.5 months (95% CI, 6.6-not reached [NR]) compared with 6.6 months (95% CI, 3.0-NR) among patients without an objective response (P = .002).

At cutoff, 12 of the 43 patients in the treatment-status analysis remained on therapy, and 31 patients had discontinued. Reasons for discontinuation included disease progression (n = 16), AEs (n = 6), loss to follow-up (n = 3), investigator judgment (n = 3), surgery (n = 2), and withdrawal of consent (n = 1).

What safety findings were reported?

The most common treatment-emergent AEs (TEAEs) in the safety population (n = 46) were anemia (58.7%), hypertriglyceridemia (32.6%), nausea (30.4%), decreased neutrophil count (28.3%), decreased leukocyte count (23.9%), and increased blood bilirubin level (21.7%). Decreased platelet count and vomiting each occurred in 19.6% of patients.

Grade 3 or higher TEAEs included anemia and decreased neutrophil count (8.7% each), decreased leukocyte count (6.5%), and increased bilirubin and decreased platelet count (4.3% each). Grade 3 or higher hypertriglyceridemia, proteinuria, increased alanine aminotransferase level, intestinal obstruction, pulmonary infection, immune-mediated hepatitis, immune-mediated dermatitis, gastrointestinal hemorrhage, and heart failure each occurred in 2.2% of patients.

References

1. Lin Z. Latest efficacy and safety analysis of surufatinib combined with EP regimen and serplulimab as first-line treatment for extrapulmonary neuroendocrine carcinoma. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 2394RO. https://www.esmo.org/meeting-calendar/esmo-congress-2026/
2. A single-arm, open-label, clinical trial of surufatinib/serplulimab/platinum/etoposide in neuroendocrine carcinoma. ClinicalTrials.gov. Updated July 14, 2026. Accessed October 23, 2026.
   https://clinicaltrials.gov/study/NCT05747729