Time-of-Day of Immunotherapy Infusion in Neoadjuvant Immunochemotherapy for Thoracic ESCC

NCT07452601 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT20260122
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multi-cohort, exploratory clinical study designed to evaluate the efficacy and safety of neoadjuvant adebrelimab combined with chemotherapy in patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC), with a particular focus on the effect of the time-of-day of immunotherapy infusion. Eligible patients with histologically or cytologically confirmed, resectable locally advanced thoracic ESCC will be randomly assigned in a 1:1:1 ratio to three cohorts according to predefined immunotherapy infusion time windows. Cohort A will receive adebrelimab plus chemotherapy with the first cycle initiated at or after 15:00 and subsequent cycles initiated before 15:00; Cohort B will receive all three cycles initiated before 15:00; and Cohort C will receive all three cycles initiated at or after 15:00. Neoadjuvant treatment consists of three cycles of adebrelimab in combination with nab-paclitaxel and cisplatin, followed by surgical resection 4-6 weeks after completion of neoadjuvant therapy. The primary endpoint of the study is pathological complete response (pCR). Secondary endpoints include event-free survival (EFS), major pathological response (MPR) rate, R0 resection rate, overall survival (OS), and disease-free survival (DFS). Tumor response will be assessed according to RECIST version 1.1, and pathological response will be evaluated using the College of American Pathologists (CAP) tumor regression grading system and AJCC 8th edition staging criteria. Safety will be continuously monitored throughout the study, and patients will undergo scheduled follow-up for disease progression or recurrence and survival after completion of study treatment.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

ESCC; Time-of-Day; Neoadjuvant; Adebrelimab

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  Pathological detection after surgery within 1 month

Secondary Outcomes (3)

• Major pathological response rate (MPR)

  Pathological detection after surgery within 1 month

• Event-free survival (EFS)

  from randomization to disease progression that makes surgery impossible, postoperative disease progression, local or distant recurrence, or death from any cause (whichever occurs first，assessed up to 60 months)

• Overall survival（OS）

  from randomization to death from any cause，assessed up to 60 months

Study Arms (3)

First Cycle After 15:00, Subsequent Cycles Before 15:00

EXPERIMENTAL

Patients receive neoadjuvant therapy with adebrelimab plus nab-paclitaxel and cisplatin for three cycles. The first cycle of immunotherapy plus chemotherapy is initiated at or after 15:00; the second and third cycles are initiated before 15:00.

Drug: Adebrelimab plus nab-paclitaxel and cisplatin

All Cycles Before 15:00

EXPERIMENTAL

Patients receive neoadjuvant therapy with adebrelimab plus nab-paclitaxel and cisplatin for three cycles. All three cycles of immunotherapy plus chemotherapy are initiated before 15:00.

Drug: Adebrelimab plus nab-paclitaxel and cisplatin

All Cycles After 15:00

EXPERIMENTAL

Patients receive neoadjuvant therapy with adebrelimab plus nab-paclitaxel and cisplatin for three cycles. All three cycles of immunotherapy plus chemotherapy are initiated at or after 15:00.

Drug: Adebrelimab plus nab-paclitaxel and cisplatin

Interventions

Adebrelimab plus nab-paclitaxel and cisplatin DRUG

Patients receive neoadjuvant therapy with adebrelimab in combination with nab-paclitaxel and cisplatin for three 21-day cycles. Immunochemotherapy is administered intravenously according to the assigned cohort's immunotherapy infusion timing. Surgery is planned 4-6 weeks after completion of neoadjuvant therapy.

All Cycles After 15:00; All Cycles Before 15:00; First Cycle After 15:00, Subsequent Cycles Before 15:00

Eligibility Criteria

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

You may qualify if:

• Patients who have signed a written informed consent form and voluntarily agree to participate in the study.
• Histologically or cytologically confirmed esophageal squamous cell carcinoma.
• Tumor located in the thoracic esophagus, assessed by CT, MRI, EUS, or other imaging modalities, with clinical stage T1b-4aN+M0 or T2-4N0M0 (T2N0 patients must have high-risk features: lymphovascular invasion \[LVI\], tumor ≥3 cm, or poor differentiation) according to AJCC 8th edition.
• Tumors deemed potentially resectable with R0 margins.
• Age between 18 and 75 years, male or female.
• ECOG performance status of 0 or 1.
• No prior anti-tumor treatment for esophageal cancer, including surgery, radiotherapy, or chemotherapy.
• Planned to undergo surgery after completion of neoadjuvant therapy.
• No contraindications to surgery.
• Adequate organ function, including:
• Hematologic parameters(no blood products, growth factors, erythropoiesis-stimulating agents, or platelet-stimulating drugs within 14 days prior to first study drug administration): Absolute neutrophil count ≥1.5 × 10⁹/L;Platelet count ≥100 × 10⁹/L;Hemoglobin ≥90 g/L.
• Biochemical parameters:Total bilirubin ≤1.5 × ULN; ALT ≤2.5 × ULN, AST ≤2.5 × ULN;Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min.
• Coagulation parameters:International normalized ratio (INR) ≤1.5 × ULN; Activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• For women of childbearing potential, a negative serum pregnancy test within 72 hours prior to first study drug administration and agreement to use effective contraception during the study and for at least 3 months after the last dose (e.g., intrauterine device, oral contraceptives, or condoms). Male participants with partners of childbearing potential must be surgically sterilized or agree to use effective contraception during the study and for at least 3 months after the last dose.
• Good compliance and willingness to adhere to study procedures and follow-up. ---

You may not qualify if:

• Tumor with obvious invasion of adjacent critical structures, such as the aorta or trachea.
• Presence of supraclavicular lymph node metastasis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Poor nutritional status with body mass index (BMI) \<18.5 kg/m²; patients whose nutritional status is corrected before randomization through supportive care may be considered eligible at the discretion of the principal investigator.
• Known hypersensitivity to monoclonal antibodies, adebrelimab, nab-paclitaxel, cisplatin, or other platinum-based agents.
• Prior or ongoing treatments as follows:
• Any prior anti-tumor therapy, including chemotherapy, radiotherapy, or other anti-cancer drugs;
• Use of systemic immunosuppressive therapy or corticosteroids for immunosuppression (\>10 mg/day prednisone or equivalent) within 2 weeks prior to first study drug administration. Inhaled or local steroid use and corticosteroid replacement therapy \>10 mg/day prednisone equivalent in patients without active autoimmune disease are permitted;
• Administration of live attenuated vaccines within 4 weeks prior to first study drug administration;
• Major surgery or severe trauma within 4 weeks prior to first study drug administration.
• Active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients on stable hormone replacement therapy may be eligible). Patients with psoriasis or childhood asthma/allergy fully resolved in adulthood and not requiring intervention may be eligible, but those requiring ongoing medical management with bronchodilators are excluded.
• History of immunodeficiency, including positive HIV test, other congenital or acquired immunodeficiency, or history of organ or allogeneic bone marrow transplantation.
• Uncontrolled clinically significant cardiac conditions, including but not limited to:
• NYHA class II or higher heart failure;Unstable angina;Myocardial infarction within 1 year;Clinically significant supraventricular or ventricular arrhythmias inadequately controlled despite intervention.
• Severe infection (CTCAE \> grade 2) within 4 weeks prior to first study drug administration requiring hospitalization, including severe pneumonia, bacteremia, or infectious complications. Patients with active pulmonary inflammation on baseline imaging, infection symptoms within 14 days prior to first study drug administration, or requiring oral/IV antibiotics (excluding prophylactic antibiotics) are excluded.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

Tangdu Hospital Affiliated to the Fourth Military Medical University

Xi'an, Shannxi, 710038, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

130-nm albumin-bound paclitaxel; Cisplatin

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2026
• First Posted: March 5, 2026
• Study Start: February 25, 2026
• Primary Completion (Estimated): February 25, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)