An Exploratory Clinical Study of Accurate Efficacy Assessment of Neoadjuvant Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma Based on 68Ga-FAPI ([68Ga] Fibroblast Activation Protein Inhibitor)/¹⁸F-FDG (2-Deoxy-2-[¹⁸F]Fluoro-D-glucose) Dual Imaging

NCT07770672 | Not Yet Recruiting Phase 2

• 1 other identifier: B2026-431R
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate whether two positron emission tomography/computed tomography (PET/CT) scans performed before treatment-68Ga-FAPI and 18F-FDG-can help predict how well patients with resectable, locally advanced thoracic esophageal squamous cell carcinoma respond to immunotherapy plus chemotherapy given before surgery. The study hypothesis is that information from the two scans can identify patients who are unlikely to have a pathologic complete response (pCR), meaning no remaining cancer in the removed esophagus or lymph nodes, and that retlirafusp alfa may improve pathologic response compared with adebrelimab when each is combined with chemotherapy in these patients. This study has two stages and plans to enroll 92 adults aged 18 to 75 years with previously untreated, stage II to IVA, resectable thoracic esophageal squamous cell carcinoma. All participants will undergo both PET/CT scans before treatment.

Conditions

Esophageal Cancer; ESCC

Keywords

PET-CT; ESCC; Neoadjuvant therapy; Adebrelimab (SHR-1316); Retlirafusp alfa (SHR-1701)

Outcome Measures

Primary Outcomes (1)

• pCR

  Complete Pathological response, no residual viable tumor cells in the primary tumor or lymph nodes.

  One week after surgery

Secondary Outcomes (5)

• MPR

  One week after surgery

• R0 resection rate

  One week after surgery

• EFS

  3 years after treatment initiation

• OS

  3 years after treatment initiation

• safty

  Within 90 days after treatment completion

Study Arms (2)

Retlirafusp Alfa Plus Chemotherapy

EXPERIMENTAL

Drug: Retlirafusp Alfa Plus Chemotherapy

Adebrelimab Plus Chemotherapy

ACTIVE COMPARATOR

Drug: Adebrelimab Plus Chemotherapy

Interventions

Retlirafusp Alfa Plus Chemotherapy DRUG

participants predicted by the 68Ga-FAPI/18F-FDG dual-imaging model to be unlikely to achieve a pathologic complete response will be randomly assigned to receive retlirafusp alfa in combination with nab-paclitaxel and cisplatin of each 3-week cycle for 2 cycles. Participants without a contraindication to surgery will undergo esophagectomy 4 to 6 weeks after the last treatment dose.

Retlirafusp Alfa Plus Chemotherapy

Adebrelimab Plus Chemotherapy DRUG

participants predicted by the 68Ga-FAPI/18F-FDG dual-imaging model to be unlikely to achieve a pathologic complete response will be randomly assigned to receive Adebrelimab in combination with nab-paclitaxel and cisplatin of each 3-week cycle for 2 cycles. Participants without a contraindication to surgery will undergo esophagectomy 4 to 6 weeks after the last treatment dose.

Adebrelimab Plus 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:

• Participants must meet all of the following criteria to be eligible for enrollment:
• Voluntarily agree to participate in the study and provide written informed consent.
• Histologically or cytologically confirmed esophageal squamous cell carcinoma.
• Thoracic esophageal cancer assessed by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), or other appropriate imaging, with clinical stage II to IVA disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.
• Considered by a surgeon to be suitable for an R0 resection and planned to undergo surgery after completing neoadjuvant treatment.
• Undergo both 18F-FDG and 68Ga-FAPI PET/CT imaging at baseline. For Stage 2, the participant's 18F-FDG and 68Ga-FAPI PET/CT parameters must meet the criteria of the prediction model for lack of pathologic complete response (non-pCR).
• Aged 18 to 75 years, inclusive, with no restriction based on sex.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• No previous antitumor treatment for esophageal cancer, including radiotherapy, chemotherapy, surgery, or other antitumor treatment.
• No contraindication to surgery.
• Adequate major organ function, as defined by all of the following:
• Hematologic function. No blood components, hematopoietic growth factors, leukocyte-elevating agents, platelet-elevating agents, or medications used to correct anemia are permitted within 14 days before the first administration of study treatment:
• Absolute neutrophil count ≥1.5 × 10\^9/L;
• Platelet count ≥100 × 10\^9/L;
• Hemoglobin ≥90 g/L.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• Obvious invasion by the tumor or involved lymph nodes into organs adjacent to the esophageal lesion, including the pleura, pericardium, azygos vein, diaphragm, peritoneum, major arteries, vertebral body, or trachea.
• Supraclavicular lymph node metastasis.
• Diagnosis of another malignant tumor within 5 years before the first administration of study treatment, except for a malignancy with a low risk of metastasis or death and an expected 5-year survival rate greater than 90%. Participants with adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, or a similar malignancy may be considered eligible.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Poor nutritional status, defined as a body mass index (BMI) of less than 18.5 kg/m2. A participant whose nutritional status is corrected through appropriate nutritional support before the initiation of treatment may still be considered eligible following assessment by the principal investigator.
• History of an allergic reaction to a monoclonal antibody.
• Receipt of any tumor-directed radiotherapy, chemotherapy, or other antitumor medication.
• Use of immunosuppressive medication or systemic corticosteroid treatment for an immunosuppressive purpose within 2 weeks before the first administration of study treatment at a dose greater than 10 mg/day of prednisone or an equivalent dose. In the absence of an active autoimmune disease, inhaled or topical corticosteroids and adrenal corticosteroid replacement at a dose greater than 10 mg/day of prednisone or an equivalent dose are permitted.
• Receipt of a live attenuated vaccine within 4 weeks before the first administration of study treatment.
• Major surgery or severe trauma within 4 weeks before the first administration of study treatment.
• Any active autoimmune disease or history of an autoimmune disease, including but not limited to interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism. Participants with hypothyroidism may be considered eligible after hormone replacement therapy. Participants with psoriasis or childhood asthma or allergy that has completely resolved and requires no intervention during adulthood may be considered eligible; however, participants requiring medical intervention with a bronchodilator are not eligible.
• History of immunodeficiency, including a positive human immunodeficiency virus (HIV) test, another acquired or congenital immunodeficiency disorder, a history of organ transplantation, or a history of allogeneic bone marrow transplantation.
• Poorly controlled cardiac symptoms or disease, including but not limited to:
• New York Heart Association (NYHA) class II or higher heart failure;

Sponsors & Collaborators

• Tan Lijie: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, China

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Han Tang

CONTACT

021-64041990; tang.han@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: August 14, 2026
• First Posted: August 18, 2026
• Study Start: August 20, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: August 18, 2026

Record last verified: 2026-08

Locations

CN (1)