Starting chemo plus PD-1 immunotherapy before radiation versus giving chemo during radiation for unresectable locally advanced esophageal squamous cell carcinoma

Efficacy and Safety of Induction Chemo-Immunotherapy Followed by Radiotherapy vs Concurrent Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized, Two-Arm, Phase II Study

PHASE2 · Second Affiliated Hospital of Zunyi Medical University · NCT07559045

This trial sees if giving three cycles of chemotherapy with a PD-1 immunotherapy before radiation, followed by maintenance immunotherapy, works better than giving chemotherapy at the same time as radiation followed by the same maintenance for people with unresectable locally advanced esophageal squamous cell carcinoma.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment92 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorSecond Affiliated Hospital of Zunyi Medical University (other)
Drugs / interventionschemotherapy, immunotherapy
Locations1 site (Zunyi, Guizhou)
Trial IDNCT07559045 on ClinicalTrials.gov

What this trial studies

This is a randomized phase II trial that will assign eligible patients with unresectable stage III-IVA esophageal squamous cell carcinoma 1:1 to two treatment strategies. The experimental arm receives three cycles of induction chemo-immunotherapy (chemotherapy plus a PD-1 antibody), then definitive thoracic radiotherapy and up to one year of PD-1 antibody maintenance; the control arm receives concurrent chemo-radiotherapy followed by the same maintenance. The co-primary endpoints are complete response rate at 3 months after radiotherapy and 1-year progression-free survival, with secondary endpoints including overall survival, objective response rate, recurrence-free measures, quality of life, and safety. The trial aims to determine whether sequencing immunotherapy before radiotherapy can improve local control and longer-term outcomes compared with the current concurrent approach.

Who should consider this trial

Good fit: Adults with histologically confirmed unresectable stage III-IVA esophageal squamous cell carcinoma, ECOG 0-1, adequate organ function, measurable disease per RECIST 1.1, and who can provide informed consent are eligible.

Not a fit: Patients with resectable tumors, prior chest radiotherapy or prior systemic therapy for ESCC, poor performance status, major uncontrolled comorbidities, or known hypersensitivity to the study drugs are unlikely to benefit or are ineligible.

Why it matters

Potential benefit: If successful, this approach could increase complete response rates and 1-year progression-free survival, potentially reducing recurrence and improving survival for these patients.

How similar studies have performed: Prior studies adding PD-1 inhibitors to concurrent chemoradiotherapy have shown promising activity, but optimal sequencing of immunotherapy with radiotherapy remains unproven.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Histologically or cytologically confirmed unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Adequate organ function (bone marrow, liver, renal, cardiac) within 2 weeks prior to randomization
* Measurable or evaluable disease per RECIST 1.1
* Willing to provide written informed consent

Exclusion Criteria:

* Previous radiotherapy to the chest or previous systemic chemotherapy for ESCC
* History of other malignancies within the last 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
* Severe comorbidities (uncontrolled hypertension, NYHA class III-IV heart failure, active infection, etc.)
* Known hypersensitivity to any study drugs (paclitaxel, cisplatin/carboplatin, PD-1 antibody)
* Pregnant or lactating women
* Participation in another clinical trial within 30 days prior to randomization

Where this trial is running

Zunyi, Guizhou

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Esophageal Squamous Cell Carcinoma, Chemo-Immunotherapy, Induction Therapy, Concurrent Chemoradiotherapy, PD-1 Inhibitor

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.