Retlirafusp Alfa Combined With Chemoradiotherapy in Unresectable ESCC

NCT07769866 | Not Yet Recruiting DMC

• 1 other identifier: LY2026-128-A
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of retlirafusp alfa combined with radical chemoradiotherapy in the treatment of locally advanced unresectable esophageal squamous cell carcinoma. Participants will receive two cycles of retlirafusp alfa and chemotherapy for induction therapy before standard concurrent chemoradiotherapy and retlirafusp alfa for maintenance treatment till one year.

Conditions

Esophageal Squamous Cell Cancer

Keywords

Esophageal Squamous Cell Cancer; PD-L1; TGF-β; Retlirafusp Alfa; SHR-1701; concurrent chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• 1 year progression-free survival (PFS) rate

  Progression-free survival (PFS) is defined as the time from the date of first study treatment administration to the first documented disease progression (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)) or death from any cause, whichever occurs first. The 1-year PFS rate is the proportion of participants who are alive and progression-free at 1 year (12 months) after the first dose.

  From the date of first study treatment administration until the date of first documented progression or death from any cause, whichever comes first, assessed up to 1 year (12 months).

Study Arms (1)

Retlirafusp Alfa Combined With Chemoradiotherapy

EXPERIMENTAL

Participants will receive two cycles of retlirafusp alfa and chemotherapy for induction therapy before standard concurrent chemoradiotherapy and retlirafusp alfa for maintenance treatment till one year

Drug: Induction chemo-immunotherapy; Radiation: Concurrent chemoradiotherapy (cCRT); Drug: maintenance immunotherapy

Interventions

Induction chemo-immunotherapy DRUG

Participants will receive two cycles of retlirafusp alfa and chemotherapy for induction therapy: Retlirafusp alfa 1800mg Day1 + Albumin-bound paclitaxel 125mg/m² Day 1 and Day 8 + Cisplatin 25mg/m² Day 1-3 every 3 weeks (Q3w)

Retlirafusp Alfa Combined With Chemoradiotherapy

Concurrent chemoradiotherapy (cCRT) RADIATION

Radiation: 1.8Gy/Fx, total dose (DT) 50.4Gy/28Fx; Chemotherapy: Albumin-bound paclitaxel 60-80mg/m² + Cisplatin 25mg/m² Day 1 every week (Qw)

Retlirafusp Alfa Combined With Chemoradiotherapy

maintenance immunotherapy DRUG

Retlirafusp Alfa 1800 mg on Day 1, Q3W, as maintenance therapy until disease progression or unacceptable toxicity, for up to 1 year; the total number of cycles for Retlirafusp Alfa induction and maintenance therapy should not exceed 15 cycles.

Retlirafusp Alfa Combined With Chemoradiotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntarily sign the written informed consent form and agree to participate in this study;
• Pathologically confirmed esophageal squamous cell carcinoma;
• Staged as T2-4bN0-3M0 or TXNXM1 (with supraclavicular lymph node metastasis), diagnosed as unresectable locally advanced esophageal cancer (according to the American Joint Committee on Cancer (AJCC) 8th edition);
• Aged 18-75 years, male or female;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, surgery, etc.;
• Adequate major organ function, meeting the following laboratory criteria:
• Complete blood count: Neutrophil count ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L; Blood biochemistry: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min; Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
• Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug, and must use effective contraception during the study period and for at least 3 months after the last dose; Male patients with female partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study period and for 3 months after the last dose.

You may not qualify if:

• Prior or concurrent treatment with any of the following:
• Any prior or ongoing radiotherapy, chemotherapy, or other anti-tumor agents for malignancy;
• Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (at a dose \> 10 mg/day of prednisone or equivalent) within 2 weeks prior to the first dose of study drug. Inhaled or topical corticosteroids, and adrenal hormone replacement at doses \> 10 mg/day prednisone or equivalent, are permitted in the absence of active autoimmune disease;
• Receipt of live attenuated vaccines within 4 weeks prior to the first dose of study drug;
• Major surgery or severe trauma within 4 weeks prior to the first dose of study drug;
• Non-esophageal cancer patients;
• Patients without unresectable locally advanced or metastatic esophageal cancer;
• Diagnosis of another malignancy within 5 years prior to the first dose of study drug, with the exception of cured cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer treated with radical surgery, and ductal carcinoma in situ treated with radical surgery;
• Other criteria:
• Poorly controlled cardiac symptoms or diseases, including: a) New York Heart Association (NYHA) class ≥ 2 heart failure; b) Unstable angina; c) Myocardial infarction within 1 year; d) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Patients with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be included; asthma requiring bronchodilators for medical intervention is excluded;
• Pregnant or breastfeeding women;
• History of severe allergic reactions to monoclonal antibodies, platinum agents, paclitaxel, or human serum albumin;
• Human immunodeficiency virus (HIV)-positive patients, or patients with active hepatitis (hepatitis B reference: hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA (HBV DNA) ≥ 2000 IU/mL or ≥ 10⁴ copies/mL; hepatitis C reference: hepatitis C virus (HCV) antibody positive), or active pulmonary tuberculosis;
• Any other condition that, in the investigator's judgment, may necessitate premature termination from the study.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Radiation Oncology Department, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Chemoradiotherapy

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)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Central Study Contacts

Xiumei Ma

CONTACT

86-021-68383624; sallyma1201@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)