ESCC, Esophageal Cancer
Conditions
Keywords
PET-CT, ESCC, Neoadjuvant therapy, Adebrelimab (SHR-1316), Retlirafusp alfa (SHR-1701)
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.
Interventions
DRUGRetlirafusp Alfa Plus Chemotherapy
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.
DRUGAdebrelimab Plus Chemotherapy
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.
Sponsors
Tan Lijie
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be eligible for enrollment: 1. Voluntarily agree to participate in the study and provide written informed consent. 2. Histologically or cytologically confirmed esophageal squamous cell carcinoma. 3. 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. 4. Considered by a surgeon to be suitable for an R0 resection and planned to undergo surgery after completing neoadjuvant treatment. 5. 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). 6. Aged 18 to 75 years, inclusive, with no restriction based on sex. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 8. No previous antitumor treatment for esophageal cancer, including radiotherapy, chemotherapy, surgery, or other antitumor treatment. 9. No contraindication to surgery. 10. Adequate major organ function, as defined by all of the following: 1. 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. 2. Biochemical function: * Total bilirubin ≤1.5 × the upper limit of normal (ULN); * Alanine aminotransferase (ALT) ≤2.5 × ULN and aspartate aminotransferase (AST) ≤2.5 × ULN; * Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min, calculated using the Cockcroft-Gault formula. 3. Coagulation function: * International normalized ratio (INR) ≤1.5 × ULN; * Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. 4. Pulmonary function: * Forced expiratory volume in 1 second (FEV1) ≥1.2 L; * FEV1 percentage of predicted value (FEV1%) ≥50%; * Diffusing capacity of the lung for carbon monoxide (DLCO) ≥50%. 11. A female participant of childbearing potential must have a negative serum pregnancy test within 72 hours before the first administration of study treatment, must not be breastfeeding, and must agree to use a highly effective method of contraception with an annual failure rate of less than 1%, such as an intrauterine device, oral contraceptive, or condom, throughout the study and until 2 months after the last dose of adebrelimab or 6 months after the last dose of chemotherapy, whichever is longer. A male participant with a female partner of childbearing potential must be surgically sterile or agree to use an effective method of contraception throughout the study and until 2 months after the last dose of adebrelimab or 3 months after the last dose of chemotherapy, whichever is longer. Sperm donation is not permitted during the study. 12. Able and willing to comply with the study procedures and follow-up requirements.
Exclusion criteria
Participants meeting any of the following criteria will be excluded: 1. 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. 2. Supraclavicular lymph node metastasis. 3. 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. 4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 5. 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. 6. History of an allergic reaction to a monoclonal antibody. 7. Receipt of any tumor-directed radiotherapy, chemotherapy, or other antitumor medication. 8. 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. 9. Receipt of a live attenuated vaccine within 4 weeks before the first administration of study treatment. 10. Major surgery or severe trauma within 4 weeks before the first administration of study treatment. 11. 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. 12. 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. 13. Poorly controlled cardiac symptoms or disease, including but not limited to: * New York Heart Association (NYHA) class II or higher heart failure; * Unstable angina; * Myocardial infarction within the previous year; * Clinically significant supraventricular or ventricular arrhythmia that has not received appropriate clinical intervention or remains poorly controlled after clinical intervention. 14. A serious infection of greater than Grade 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) within 4 weeks before the first administration of study treatment, including severe pneumonia requiring hospitalization, bacteremia, or other serious infectious complications; evidence of active pulmonary inflammation on baseline chest imaging; signs or symptoms of infection within 14 days before the first administration of study treatment; or a requirement for oral or intravenous antibiotic treatment within that period. Prophylactic antibiotic use is permitted. 15. Active tuberculosis identified through medical history or CT examination; a history of active tuberculosis within 1 year before enrollment; or a history of active tuberculosis more than 1 year before enrollment without having received appropriate standard treatment. 16. Active hepatitis B, defined as hepatitis B virus DNA ≥2,000 IU/mL or ≥10\^4 copies/mL; or hepatitis C, defined as a positive hepatitis C virus antibody test together with hepatitis C virus RNA above the lower limit of detection of the assay. 17. Pregnant or breastfeeding female participants. 18. Any other factor that, in the investigator's judgment, may result in forced premature discontinuation from the study, including another serious illness requiring concomitant treatment, including a psychiatric disorder; alcohol abuse; drug abuse; or family or social circumstances that may affect the participant's safety or compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | One week after surgery | Complete Pathological response, no residual viable tumor cells in the primary tumor or lymph nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MPR | One week after surgery | Major Pathological Response, the residual tumor cells in the primary tumor were less than 10%. |
| R0 resection rate | One week after surgery | Both ends and circumferential margins were negative |
| EFS | 3 years after treatment initiation | Event-free survival (EFS) was assessed by the investigator per RECIST 1.1 and was defined as the time from randomization to the occurrence of a study-defined event. |
| OS | 3 years after treatment initiation | Overall survival (OS) was defined as the time from randomization to death from any cause. |
| safty | Within 90 days after treatment completion | incidence of adverse events and surgical complications during treatment |
Countries
China
Contacts
CONTACTHan Tang
Outcome results
None listed