Retlirafusp Alfa Plus Chemotherapy as Neoadjuvant Therapy for Thoracic ESCC

NCT07618910 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026043
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, exploratory clinical study designed to evaluate the efficacy and safety of retlirafusp alfa combined with chemotherapy (nab-paclitaxel and cisplatin) as a neoadjuvant therapy for patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC). The primary objective of this study is to assess the pathologic complete response (pCR) rate in the target population. A total of 33 patients with histologically or cytologically confirmed resectable locally advanced thoracic ESCC are planned to be enrolled.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

ESCC; Retlirafusp alfa; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  Pathological detection after surgery within 1 month

Secondary Outcomes (4)

• 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 36 months)

• Overall survival（OS）

  from randomization to death from any cause，assessed up to 36 months

• R0 Resection Rate

  after surgery within 1 month

Study Arms (1)

Retlirafusp Alfa plus Nab-Paclitaxel and Cisplatin

EXPERIMENTAL

Subjects will receive 3 cycles of neoadjuvant therapy. The regimen consists of Retlirafusp alfa combined with nab-paclitaxel and cisplatin. A dosing window of 3 days is allowed during the treatment period. Prior to each administration (within 3 days before dosing), standard safety evaluations, including physical examinations, laboratory tests, and ECOG performance status assessments, must be completed to confirm treatment tolerance. Following the completion of the 3-cycle neoadjuvant therapy, surgical resection will be performed after a rest period of 4 to 6 weeks. Safety, tumor progression/recurrence, and overall survival will be continuously monitored during the follow-up period.

Drug: Retlirafusp alfa; Drug: Nab paclitaxel; Drug: Cisplatin for injection

Interventions

Retlirafusp alfa DRUG

Administered at a fixed dose of 1800 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W), for a total of 3 cycles. Retlirafusp alfa must be infused first in the sequence, with an interval of at least 30 minutes before the subsequent administration of nab-paclitaxel.

Retlirafusp Alfa plus Nab-Paclitaxel and Cisplatin

Nab paclitaxel DRUG

Administered at a dose of 130 mg/m² via intravenous (IV) infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 3 cycles.

Retlirafusp Alfa plus Nab-Paclitaxel and Cisplatin

Cisplatin for injection DRUG

Administered at a dose of 75 mg/m² via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W), for a total of 3 cycles.

Retlirafusp Alfa plus Nab-Paclitaxel and Cisplatin

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 signed and dated written informed consent to participate in this study.
• Histologically or cytologically confirmed esophageal squamous cell carcinoma (ESCC).
• Clinically staged as thoracic ESCC evaluated by CT, MRI, or endoscopic ultrasonography (EUS), with a clinical stage of T1b-4aN+M0 or T2-4N0M0 according to the American Joint Committee on Cancer (AJCC) 8th edition. For T2N0 patients, at least one high-risk factor must be present: lymphovascular invasion (LVI), tumor size \>= 3 cm, or poor differentiation.
• Anticipated to achieve an R0 resection.
• Age between 18 and 75 years (inclusive) at the time of signing the informed consent, of either sex.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, or surgery.
• Planned to undergo definitive surgical resection following the completion of neoadjuvant therapy.
• No contraindications to surgical resection.
• Adequate major organ functions, meeting the following laboratory criteria: 10a) Hematology (no blood components, cell growth factors, leukogenic agents, platelet-stimulating agents, or anemia-correcting therapies allowed within 14 days prior to the first dose of study drug): Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Platelet count \>= 100 x 10\^9/L; Hemoglobin \>= 90 g/L. 10b) Blood Biochemistry: Total bilirubin (TBIL) \<= 1.5 x Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) \<= 2.5 x ULN; Aspartate aminotransferase (AST) \<= 2.5 x ULN; Serum creatinine \<= 1.5 x ULN, or creatinine clearance (CrCl) \>= 50 mL/min. 10c) Coagulation Function: International Normalized Ratio (INR) \<= 1.5 x ULN; Activated Partial Thromboplastin Time (APTT) \<= 1.5 x ULN.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug and agree to use highly effective methods of contraception (e.g., intrauterine device \[IUD\], contraceptives, or condoms) during the trial and for at least 3 months after the last dose. Male subjects whose partners are females of childbearing potential must be surgically sterile or agree to use highly effective contraception during the trial and for at least 3 months after the last dose.
• Good compliance and willingness to cooperate with the scheduled follow-up visits.

You may not qualify if:

• Tumors with clear invasion into adjacent organs of the esophageal lesion (e.g., aorta or trachea).
• Presence of supraclavicular lymph node metastasis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage.
• Poor nutritional status with Body Mass Index (BMI) \< 18.5 kg/m2; however, patients whose nutritional status is corrected after symptomatic nutritional support before enrollment may still be considered after evaluation by the principal investigator.
• Known history of hypersensitivity to the study drugs.
• Prior or current receipt of any of the following treatments: 6a) Any prior anti-tumor radiotherapy, chemotherapy, or other anti-tumor medications. 6b) Use of immunosuppressive medications or systemic corticosteroid therapy for immunosuppressive purposes (dose \> 10 mg/day of prednisone or equivalent dose) within 2 weeks prior to the first dose of study drug. 6c) Receipt of live attenuated vaccines within 4 weeks prior to the first dose of study drug. 6d) Major surgery or severe trauma within 4 weeks prior to the first dose of study drug.
• History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
• Uncontrolled clinical cardiac symptoms or diseases, including but not limited to: (1) New York Heart Association (NYHA) Class II or higher heart failure, (2) unstable angina, (3) myocardial infarction within the past 1 year, (4) clinically significant supraventricular or ventricular arrhythmias that are uncontrolled or poorly controlled despite clinical intervention.
• Severe infection (CTCAE \> Grade 2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia, bacteremia, or infectious complications requiring hospitalization; baseline chest imaging indicating active pulmonary inflammation, signs or symptoms of infection within 14 days prior to the first dose of study drug, or requiring oral or intravenous antibiotic therapy (except for prophylactic antibiotic use).
• Active tuberculosis infection detected by medical history or CT scan, or a history of active tuberculosis infection within 1 year prior to enrollment, or a history of active tuberculosis infection more than 1 year ago without formal standard treatment.
• Screening imaging showing tumor encasement of major blood vessels or significant necrosis/cavitation, where the investigator judges that study participation would pose a high risk of hemorrhage.
• Active hepatitis B (HBV DNA \>= 2000 IU/mL or 10\^4 copies/mL), or hepatitis C (HCV antibody positive and HCV RNA above the lower limit of detection of the assay).
• Diagnosis of other malignant tumors within 5 years prior to the first dose of study drug, unless the malignancy carries a low risk of metastasis or death (5-year survival rate \> 90%), such as adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ.
• Pregnant or lactating females.
• Any other factors that, in the judgment of the investigator, may compel premature termination of study participation, such as other severe medical or psychiatric conditions requiring concomitant therapy, alcohol abuse, drug abuse, familial or social factors, or any other conditions that may compromise subject safety or compliance.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

Tangdu Hospital Affiliated to the Fourth Military Medical University

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Taxes; Cisplatin; Injections

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)

Economics; Health Care Economics and Organizations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Xiaolong Yan, Dr

CONTACT

029-847171569; yanxiaolong@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2026
• First Posted: June 1, 2026
• Study Start: May 30, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

CN (1)