Low-Dose Radiotherapy With Retlirafusp Alfa and Chemotherapy as Neoadjuvant Therapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

NCT07682376 | Active Not Recruiting Phase 2

• 1 other identifier: MA-EC-II-032
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of neoadjuvant low-dose radiotherapy combined with Retlirafusp alfa and chemotherapy in the treatment of resectable locally advanced esophageal squamous cell carcinoma.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal Squamous Cell Carcinoma; Retlirafusp alfa; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  pCR is defined as the absence of residual invasive carcinoma cells in both the resected primary tumor and lymph nodes.

  Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

Secondary Outcomes (9)

• Major Pathological Response (MPR)

  Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

• R0 Resection Rate

  Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; follow-up up to 6 months.

• Objective Response Rate (ORR)

  Assessed via imaging after completion of neoadjuvant therapy; follow-up up to 6 months.

• Disease Control Rate (DCR)

  Assessed via imaging after completion of neoadjuvant therapy; follow-up up to 6 months.

• Event-Free Survival (EFS)

  From enrollment to first event, assessed every 3 months; follow-up up to 36 months.

Study Arms (2)

Low-dose radiotherapy + Retlirafusp alfa + chemotherapy

EXPERIMENTAL

Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin

Drug: Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin

Retlirafusp alfa + chemotherapy

EXPERIMENTAL

Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin

Drug: Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin

Interventions

Low-dose radiotherapy + Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin DRUG

Low-dose radiotherapy: 8 Gy in 4 fractions, 2 Gy per fraction, targeting the primary tumor and metastatic lymph nodes. Retlirafusp alfa: 1800 mg or 30 mg/kg on D1, q3w, for 2 cycles. Nab-paclitaxel: 125 mg/m² on D1 and D8, plus cisplatin 75 mg/m² on D1 or carboplatin AUC=5 on D1, q3w, for 2 cycles.

Low-dose radiotherapy + Retlirafusp alfa + chemotherapy

Retlirafusp alfa + nab-paclitaxel + cisplatin/carboplatin DRUG

Retlirafusp alfa: 1800 mg or 30 mg/kg on D1, q3w, for 2 cycles. Nab-paclitaxel: 125 mg/m² on D1 and D8, plus cisplatin 75 mg/m² on D1 or carboplatin AUC=5 on D1, q3w, for 2 cycles.

Retlirafusp alfa + chemotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntary participation with written informed consent.
• Age 18-75 years, male or female.
• Histologically or cytologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
• Clinical stage T1-4aN1-3M0 or T3-4aN0M0 (AJCC 9th edition): T stage determined by CT combined with MRI or endoscopic ultrasound; nodal involvement confirmed by biopsy, EBUS/EUS, or mediastinoscopy, or imaging showing lymph node short-axis diameter ≥2.0 cm; distant metastasis (M1) excluded by FDG-PET/CT or chest/abdominal/brain CT/MRI; no suspicious metastatic lymph nodes on cervical ultrasound.
• Potentially resectable thoracic esophageal lesion with anticipated R0 resection.
• No prior systemic therapy for esophageal tumor (chemotherapy, targeted therapy, immunotherapy, radiotherapy, etc.).
• ECOG performance status 0-1.
• At least one measurable lesion per Japanese Classification of Esophageal Cancer, 12th edition.
• Agreement to provide archived tumor tissue or undergo biopsy for biomarker analysis.
• Adequate organ function (within 14 days prior to first dose, without blood products or growth factors):
• Hematology: WBC ≥4×10⁹/L, ANC ≥2×10⁹/L, hemoglobin ≥90 g/L, platelets ≥90×10⁹/L.Hepatic: total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert's syndrome), AST and ALT ≤2.5×ULN (≤5×ULN for liver metastases), alkaline phosphatase ≤3×ULN (≤5×ULN for liver/bone metastases), albumin ≥30 g/L. Renal: serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault formula). Coagulation: INR ≤1.5 (without anticoagulation).
• Body weight \>35 kg, with no \>10% weight loss in the past 3 months.
• Life expectancy \>12 months.
• Women of childbearing potential and men must use effective contraception during the study and for 3 months after the last dose; non-lactating; negative serum/urine HCG within 7 days before first dose for women of childbearing potential.

You may not qualify if:

• History of hypersensitivity to any component of Retlirafusp alfa, paclitaxel, carboplatin, or other platinum agents.
• ,Cervical esophageal cancer, esophageal adenocarcinoma, or other pathological types.
• Clinical stage I/IIA, T4b unresectable, or distant metastasis (M1) confirmed by imaging.
• History of other malignancies within 5 years, except cured basal cell carcinoma of the skin, cervical carcinoma in situ, etc.
• Prior or current receipt of any of the following:
• Any radiotherapy, chemotherapy, or other anti-tumor therapy for malignancy.
• Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent) within 2 weeks prior to first study drug administration. Inhaled or topical steroids 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 vaccine within 4 weeks prior to first study drug administration.
• Major surgery or severe trauma within 4 weeks prior to first study drug administration.
• Active or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy). Patients with psoriasis or childhood asthma/allergy that has fully resolved and requires no intervention in adulthood may be considered; however, those requiring bronchodilators for medical intervention are excluded.
• Immunodeficiency, including HIV positivity, other acquired or congenital immune deficiencies, or history of organ or allogeneic bone marrow transplantation.
• Poorly controlled cardiac conditions, including but not limited to: (1) NYHA class ≥II heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias uncontrolled despite intervention.
• Severe infection (CTCAE grade ≥2) within 4 weeks prior to first study drug administration, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; active pulmonary inflammation on baseline chest imaging; signs/symptoms of infection or need for oral/IV antibiotics within 14 days prior to first dose (except prophylactic antibiotics).
• Active pulmonary tuberculosis by history or CT, history of active tuberculosis within 1 year prior to enrollment, or history of active tuberculosis \>1 year ago without adequate treatment.
• Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL), or hepatitis C (HCV antibody positive with HCV RNA above the lower limit of detection).

Sponsors & Collaborators

• Harbin Medical University: lead
• Henan Cancer Hospital: collaborator
• Shanxi Province Cancer Hospital: collaborator
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, China

Harbin, Heilongjiang, 150081, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Radiotherapy; 130-nm albumin-bound paclitaxel; Cisplatin; Carboplatin

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)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: July 2, 2026
• Study Start: June 10, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2029
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)