Toripalimab plus capecitabine after chemoradiotherapy for esophageal squamous cell carcinoma

Toripalimab Combined With Capecitabine as Maintenance Therapy After Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: a Multicenter, Randomized Controlled, Phase III Trial (EC-CRT-008)

This trial will test whether giving toripalimab together with low‑dose capecitabine after definitive chemoradiotherapy helps people with locally advanced esophageal squamous cell carcinoma live longer and have fewer recurrences.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 242 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, toripalimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07177794 on ClinicalTrials.gov

What this trial studies

This is a randomized, controlled, multicenter phase III trial testing consolidation therapy with toripalimab plus metronomic capecitabine after completion of definitive concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. Eligible patients have completed CRT without disease progression and are enrolled within 1–42 days after radiotherapy; most have inoperable disease or declined surgery. The trial builds on a prior phase II finding that adding toripalimab to CRT improved complete response rates and explores whether adding metronomic capecitabine can modulate the tumor immune microenvironment to synergize with PD‑1 blockade. The primary goal is to reduce recurrence and prolong survival compared with standard post‑CRT management.

Who should consider this trial

Good fit: Ideal candidates are adults (18–75) with histologically confirmed esophageal squamous cell carcinoma who completed definitive concurrent chemoradiotherapy without progression (stage I–IVA inoperable/declined surgery or stage IVB with only supraclavicular nodes), have ECOG ≤2, adequate organ function, and can enroll within 1–42 days after CRT.

Not a fit: Patients who progressed during or immediately after CRT, have non‑squamous histology, distant metastatic disease beyond supraclavicular nodes, poor performance status, or major organ dysfunction are unlikely to benefit from this consolidation approach.

Why it matters

Potential benefit: If successful, this approach could reduce recurrence and extend survival for patients after definitive chemoradiotherapy for locally advanced ESCC.

How similar studies have performed: A prior phase II at the same group showed that adding toripalimab to definitive CRT increased complete response rates, and there is preclinical and early‑clinical rationale that metronomic capecitabine can synergize with PD‑1 inhibitors, but this exact consolidation regimen is being tested in a phase III setting.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed squamous cell carcinoma of the esophagus;
2. Locally advanced esophageal cancer classified as stage I-IVA (inoperable or patient declined surgery) or stage IVB thoracic esophageal cancer with supraclavicular lymph node metastasis only (AJCC 8th edition) prior to treatment;
3. Completion of definitive concurrent chemoradiotherapy without disease progression; radiotherapy dose of 50-50.4 Gy using conventional fractionation and IMRT technique; concurrent platinum- or taxane-based doublet chemotherapy during radiotherapy; ≤4 cycles of induction chemotherapy allowed prior to radiotherapy; PD-1/PD-L1 antibody therapy permitted during induction chemotherapy and radiotherapy; no adjuvant therapy received;
4. Enrollment window: within 1-42 days after completion of chemoradiotherapy;
5. Age 18-75 years;
6. Estimated life expectancy \>6 months;
7. Eastern Cooperative Oncology Group performance status ≤ 2;
8. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥3.5×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥75×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min;
9. Ability to understand the trial details and has provided written informed consent.

Exclusion Criteria:

1. Patients who have received antitumor therapy (including adjuvant chemotherapy, surgery, immunotherapy, targeted therapy, etc.) after completion of chemoradiotherapy;
2. Stage IVb patients with metastasis to solid organs (e.g., liver, bone, lung, brain, adrenal gland, peritoneum, etc.) at initial diagnosis;
3. Known or suspected allergy to the investigational drug(s) or any agent related to the trial regimen;
4. Presence of esophageal fistula and/or esophageal hemorrhage prior to enrollment;
5. Disease progression after chemoradiotherapy;
6. ≥Grade 2 radiation pneumonitis prior to enrollment;
7. History of ≥ Grade 3 immune-related adverse events prior to enrollment;
8. Prior treatment with targeted drugs;
9. History of other malignant tumors besides esophageal cancer, except for non-melanoma skin cancer, carcinoma in situ of the cervix, papillary thyroid carcinoma, or cured early-stage prostate cancer;
10. Patients with severe cardiac, pulmonary, hepatic, or renal dysfunction, hematopoietic system diseases, cachexia, or other conditions that make them unfit for chemotherapy;
11. Female patients who are pregnant or breastfeeding;
12. Inability to provide informed consent due to psychological, familial, social, or other factors;
13. Presence of CTC grade ≥2 peripheral neuropathy;
14. Patients with a history of diabetes for more than 10 years and poorly controlled blood glucose levels;
15. History of autoimmune disease or autoimmune disorders (e.g., colitis, systemic lupus erythematosus, rheumatoid arthritis, uveitis, hypophysitis, hyperthyroidism; not limited to these diseases or syndromes), immunodeficiency history, including HIV positivity, or other acquired/congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation;
16. History of interstitial lung disease or non-infectious pneumonia;
17. 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);
18. Any unstable condition that may jeopardize patient safety or compliance.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Mian Xi, MD — Sun Yat-Sen University Cancer Center
• Study coordinator: Mian Xi, MD

Conditions Esophageal Cancer; Chemoradiotherapy; Esophageal squamous cell carcinoma; definitive chemoradiotherapy; maintenance therapy; Toripalimab