Induction immunochemotherapy followed by chemoradiotherapy for advanced esophageal squamous cell carcinoma

Induction Immunochemotherapy Followed by Concurrent Chemoradiotherapy for Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: a Stratified Exploratory Phase 2 Trial.

This plan will try two cycles of induction immunochemotherapy and then give chemoradiotherapy—adding the immunotherapy drug adebrelimab during radiation for patients who respond—to treat people with unresectable locally advanced esophageal squamous cell carcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06452602 on ClinicalTrials.gov

What this trial studies

Up to 60 patients with unresectable locally advanced esophageal squamous cell carcinoma will be enrolled at Tianjin Cancer Hospital. All participants receive two cycles of induction immunochemotherapy, after which they are split into responder (CR/PR) and nonresponder (SD/PD) groups based on tumor response. Responders receive the same immunochemotherapy plus concurrent radiotherapy (50.4 Gy in 28 fractions) with adebrelimab continued and maintenance immunotherapy for up to one year; nonresponders receive a different concurrent chemoradiotherapy regimen without immunotherapy during radiation. Tumor tissue (fresh or archived FFPE) is collected for biomarker analysis such as PD-L1 testing to inform exploratory analyses.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with histologically confirmed, inoperable locally advanced esophageal squamous cell carcinoma (stages cT1–4bN0–3M0 or supraclavicular nodal M1) who are treatment‑naïve and have ECOG 0–1.

Not a fit: Patients who have received prior systemic anti‑tumor therapy, have poor performance status, or have disease that clearly progresses despite induction immunochemotherapy are unlikely to benefit from the immunotherapy strategy tested here.

Why it matters

Potential benefit: If successful, this approach could personalize care by giving combined immunochemotherapy and radiation to patients most likely to benefit while avoiding ineffective immunotherapy in resistant cases.

How similar studies have performed: Prior trials have shown benefit from adding PD‑1/PD‑L1 inhibitors to chemotherapy or chemoradiation in some esophageal cancer settings, but using induction immunochemotherapy to stratify patients before concurrent chemoradiotherapy is a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

1. Volunteered to participate, cooperated with follow-up visits;
2. Aged 18 years or older, both male and female;
3. Histologically confirmed cT1N2-3M0 or cT2-4bN0-3M0 or cT1-4bN0-3M1( supraclavicular lymph node metastasis) locally advanced ESCC (8th AJCC );
4. Clinically staged as II-IVb inoperable locally advanced ESCC(including non-resectable, or with contraindications to or refusal of surgery);
5. ECOG performance status 0 or 1;
6. Presence of measurable and/or non-measurable lesions as defined by RECIST 1.1;
7. Haven't received any previous systemic anti-tumor therapy (including but not limited to systemic chemotherapy, radiotherapy, molecularly targeted drug therapy, immunotherapy, biologic therapy, topical therapy and other investigational therapeutic agents);
8. Provide fresh or archived tumour tissue samples within 6 months (fresh samples preferred) for biomarker analysis (e.g.PD-L1). Sample types are formalin-fixed, paraffin-embedded \[FFPE\] tumour tissue blocks or at least 5 unstained, 3-5 μm thick FFPE tumour tissue sections;
9. Expected survival ≥ 3 months;
10. Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin count ≥9.0 g/dl or ≥5.6 mmol/l;
11. Adequate renal function, defined as creatinine ≤1.5× ULN or measured or calculated creatinine clearance ≥60 mL/min for those with creatinine levels \>1.5× ULN (Calculated from the Cockcroft-Gault formula);
12. Adequate hepatic function, defined as total bilirubin ≤1.5× ULN and ALT/AST/AKP levels ≤2.5× ULN and albumin ≥2.8 g/dl;
13. Adequate coagulation function, defined as INR ≤1.5× ULN and APTT≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as INR is within the therapeutic range;
14. Women of childbearing potential with a negative urine pregnancy test within 3 days before the first administration of the investigational drugs.
15. Documented informed consent.

Exclusion Criteria:

1. Surgery for esophageal cancer;
2. Esophageal fistulae due to infiltration of the primary tumour;
3. Risk of gastrointestinal bleeding, oesophageal fistula or oesophageal perforation
4. Poor nutritional status, weight loss of ≥10% in the previous 2 months, with no significant improvement after nutritional intervention;
5. Major surgery or severe trauma within 4 weeks prior to first use of study drug;
6. Uncontrollable pleural effusion, pericardial effusion, or ascites that requires repeated drainage;
7. Received or receiving any of the following treatments in the past:

   1. Anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy or targeted therapy;
   2. Participation in a study of an investigational agent or device within 4 weeks before the first dose of study treatment;
   3. Systemic treatment with corticosteroids (\>10 mg prednisone equivalent dose per day) or other immunosuppressive agents is required for 2 weeks before the first dose of study treatment(except for the use of corticosteroids for local inflammation of the oesophagus and for the prevention of allergy and nausea and vomiting). Other special circumstances need to be communicated to the sponsor.Inhaled or topical steroids and adrenocorticotropic hormone replacement at doses \>10mg/day prednisone efficacy dose are permitted if the patient does not have active autoimmune disease;
   4. Received an anti-tumour vaccine or received a live vaccine within 4 weeks before the first dose of study treatment;
8. Any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism);Except for patients with vitiligo or those who had asthma or allergies in childhood but did not need any intervention as adults; patients with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type I diabetes mellitus treated with stable doses of insulin may be included;
9. Diagnosis of immunodeficiency, including positive HIV test,other acquired/congenital immunodeficiency diseases, organ transplantation and allogeneic bone marrow transplantation;
10. Diagnosis of uncontrolled cardiac clinical symptoms or disease such as a.NYHA II or above heart failure b.unstable angina c.myocardial infarction within 1 year d.clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
11. Severe infections (CTCAE \> Grade 2), such as severe pneumonia requiring hospitalisation, bacteraemia, infectious co-morbidities, etc., within 4 weeks before the first use of study treatment; Baseline chest imaging suggestive of active lung inflammation, signs and symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks before the first use of study treatment, except for prophylactic antibiotic use;
12. History of interstitial lung disease or non-infectious pneumonia, or pulmonary insufficiency ≥ grade 3 as confirmed by pulmonary function tests;
13. Active tuberculosis infection detected by history or CT examination, or history of active tuberculosis infection within 1 year before enrollment or more than 1 year previously without regular treatment;
14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the lower limit of detection);
15. Presence of abnormal sodium, potassium, and calcium laboratory test values greater than Grade 1 within 2 weeks prior to randomisation that do not improve with treatment;
16. Known hypersensitivity to large protein preparations, or to any of the components of nab-paclitaxel or carboplatin or to any of the components used within their preparations;
17. Pregnant or lactating patients.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Cancer Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Wencheng zhang, M.D. — Tianjin Cancer Hospital
• Study coordinator: Wencheng zhang, M.D.

Conditions Esophageal Cancer; Induction Immunochemotherapy; Adebrelimab; Esophageal Squamous Cell Carcinoma