Immunotherapy Plus Anlotinib After Surgery for Esophageal Squamous Cell Cancer With Residual Tumor and Positive Lymph Nodes

NCT07830355 | Not Yet Recruiting Phase 2

• 1 other identifier: IS26139
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn whether postoperative immunotherapy combined with anlotinib can help prevent or delay cancer recurrence in adults aged 18 to 75 years with locally advanced esophageal squamous cell carcinoma. Eligible participants must have previously received chemotherapy combined with anti-PD-1 immunotherapy, followed by complete surgical removal of the cancer. Examination of the surgical specimens must show more than 10% viable tumor remaining in the original tumor bed and cancer cells remaining in regional lymph nodes. The main questions this trial aims to answer are:

• What proportion of participants are alive without cancer recurrence or a second primary cancer 12 months after enrollment?
• How long do participants remain free of cancer recurrence, and how long do they survive?
• What treatment-related medical problems occur during treatment with anti-PD-1 immunotherapy plus anlotinib?
• Where does the cancer recur if recurrence occurs? All participants will receive the same study treatment; there is no comparison group. Participants will:
• Receive an anti-PD-1 immunotherapy medicine by intravenous infusion once every 3 weeks, generally using the same anti-PD-1 medicine received before surgery
• Take anlotinib by mouth once daily for 14 days, followed by 7 days without anlotinib, in each 21-day treatment cycle
• Continue treatment for up to 15 cycles unless the cancer returns, unacceptable side effects occur, consent is withdrawn, or another reason for stopping treatment arises
• Undergo regular clinic visits, laboratory tests, physical examinations, and safety assessments during treatment
• Undergo imaging examinations approximately every 3 months to check for cancer recurrence
• Be followed for disease recurrence and survival for up to 5 years after surgery Stored surgical tumor tissue will also be studied to explore whether features of the tumor immune environment are associated with treatment outcomes.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Anlotinib; Non-Major Pathological Response; ypN-Positive Disease; Adjuvant Therapy; Neoadjuvant Chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• 1-Year Disease-Free Survival Rate

  The Kaplan-Meier estimated percentage of participants who are alive without local or regional recurrence, distant metastasis, or a second primary malignancy at 12 months after enrollment. Disease-free survival is measured from the date of enrollment to the first occurrence of disease recurrence, a second primary malignancy, or death from any cause, whichever occurs first.

  At 12 months after enrollment

Secondary Outcomes (4)

• Disease-Free Survival

  From enrollment through 5 years after surgery

• Overall Survival

  From enrollment through 5 years after surgery

• Patterns of Disease Recurrence

  From enrollment through 5 years after surgery

• Percentage of Participants With Treatment-Related Adverse Events

  From the first dose through completion or discontinuation of study treatment, up to 15 cycles (each cycle is 21 days).

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Participants will receive an anti-PD-1 monoclonal antibody by intravenous infusion on Day 1 of each 21-day cycle, generally using the same anti-PD-1 agent administered during neoadjuvant treatment. Anlotinib will be administered orally at a starting dose of 12 mg once daily on Days 1-14 of each 21-day cycle. Study treatment must begin within 10 weeks after surgery and will continue for up to 15 cycles unless disease recurrence, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation occurs. Protocol-specified treatment interruptions and dose reductions of anlotinib to 10 mg or 8 mg are permitted for toxicity. Dose reduction of the anti-PD-1 agent is not permitted.

Drug: Anlotinib; Drug: Anti-PD-1 Monoclonal Antibody

Interventions

Anlotinib DRUG

Anlotinib will be administered orally at a starting dose of 12 mg once daily on Days 1-14 of each 21-day cycle. Treatment will begin concurrently with anti-PD-1 immunotherapy within 10 weeks after surgery and continue for up to 15 cycles unless disease recurrence, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion occurs. Dose interruptions and reductions to 10 mg and 8 mg once daily are permitted according to protocol-defined toxicity management criteria.

Experimental Arm

Anti-PD-1 Monoclonal Antibody DRUG

An anti-PD-1 monoclonal antibody will be administered by intravenous infusion on Day 1 of each 21-day cycle, generally using the same anti-PD-1 agent administered during neoadjuvant treatment. Treatment will begin within 10 weeks after surgery and continue for up to 15 cycles unless disease recurrence, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion occurs. Dose reduction is not permitted; treatment-related toxicity will be managed by treatment interruption or permanent discontinuation according to the protocol.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years, inclusive.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Histologically confirmed locally advanced esophageal squamous cell carcinoma.
• Prior treatment with 2 to 4 cycles of neoadjuvant chemotherapy combined with an anti-PD-1 monoclonal antibody, followed by radical surgery with pathologically confirmed R0 resection.
• An interval of no more than 10 weeks between completion of the last neoadjuvant chemotherapy or immunotherapy treatment and radical surgery.
• Postoperative pathological assessment showing non-major pathological response, defined as more than 10% residual viable tumor cells in the primary tumor bed, and viable tumor metastasis in at least one resected regional lymph node (ypN-positive disease).
• Enrollment within 10 weeks after esophagectomy.
• Ability to swallow and tolerate oral medication, without severe dysphagia, chronic diarrhea, intestinal obstruction, or another condition that may substantially affect oral drug absorption.
• Adequate organ function, based on laboratory tests performed within 7 days before the first dose and without blood transfusion, erythropoietin, granulocyte colony-stimulating factor, or similar supportive treatment within the preceding 14 days, meeting all of the following criteria:
• Absolute neutrophil count ≥1.5 × 10\^9/L.
• Platelet count ≥100 × 10\^9/L.
• Hemoglobin ≥90 g/L.
• Total bilirubin ≤1.5 × the upper limit of normal (ULN).
• Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN.
• Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min.

You may not qualify if:

• Esophageal cancer with a pathological type other than squamous cell carcinoma.
• Distant organ or distant lymph node metastasis identified by preoperative imaging, intraoperative exploration, or postoperative pathological examination, corresponding to M1 disease according to the American Joint Committee on Cancer staging system, Eighth Edition.
• No prior neoadjuvant therapy, or prior neoadjuvant therapy other than chemotherapy combined with immunotherapy, including neoadjuvant chemotherapy alone or neoadjuvant chemoradiotherapy.
• Use of an anti-PD-L1 antibody or another immune checkpoint inhibitor other than an anti-PD-1 antibody during neoadjuvant treatment.
• One or fewer, or more than four, cycles of neoadjuvant chemoimmunotherapy.
• A Grade 4 or higher immune-related adverse event, Grade 3 or higher immune-related pneumonitis, or Grade 2 or higher immune-related myocarditis during prior neoadjuvant treatment, according to the Common Terminology Criteria for Adverse Events, Version 5.0.
• Substantial extranodal extension, fixed or matted regional lymph nodes, or involvement of important surrounding tissues or organs found during surgery that, in the investigator's judgment, prevented complete oncological resection or created a clear risk of residual disease; or postoperative evidence of R1 or R2 resection.
• Major pathological response or pathologically negative regional lymph nodes (ypN0) after neoadjuvant treatment.
• A severe postoperative complication of Grade 3 or higher that has not recovered to Grade 1 or lower or to the preoperative baseline before planned adjuvant treatment or within 10 weeks after surgery; or a postoperative complication that, in the investigator's judgment, has substantially reduced the participant's performance status and is expected to prevent tolerance of adjuvant treatment.
• Poor nutritional status or a Patient-Generated Subjective Global Assessment score ≥9.
• An unhealed wound, ulcer, or fracture.
• Any Grade 2 or higher bleeding event within 4 weeks before the first dose.
• Evidence of a bleeding diathesis; current thrombolytic therapy or therapeutic anticoagulation; or use of an antiplatelet drug, such as clopidogrel, or high-dose aspirin \>325 mg/day within 14 days before the first dose. Low-dose aspirin ≤100 mg/day for cardiovascular prevention is permitted.
• An arterial or venous thromboembolic event within 6 months before the first dose, including cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or pulmonary embolism.
• A concurrent second primary malignancy or a history of another malignancy within the previous 5 years, except completely cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

anlotinib; spartalizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Jun Liu, Dr

CONTACT

+86 18930859538; drjunliuplus@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 21, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share