Neoadjuvant chemoimmunotherapy followed by endoscopic removal for esophageal squamous cell carcinoma

Safety and Feasibility of Neoadjuvant Immunotherapy Combined With Chemotherapy Sequenced With Endoscopic Resection for Esophageal Cancer (Endosurgery-02)

This trial tests whether giving chemotherapy plus the PD‑1 drug tislelizumab before surgery can shrink esophageal squamous cell cancers enough to allow removal with an organ‑preserving endoscopic procedure in adults with potentially resectable tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, tislelizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07317609 on ClinicalTrials.gov

What this trial studies

This single‑center, prospective, single‑arm phase 1 study gives adults with potentially resectable esophageal squamous cell carcinoma at least two 3‑week cycles of tislelizumab (200 mg on Day 1) combined with carboplatin (AUC 3–5 on Day 1) and nab‑paclitaxel (≤260 mg/m2 on Day 1), with routine safety monitoring. About 3–4 weeks after completing treatment, patients undergo clinical reassessment with endoscopy, endoscopic ultrasound, and CT or PET/CT to measure tumor response by RECIST 1.1 and to evaluate nodal or distant spread. If a clinical complete response is seen without obvious nodal disease, patients may undergo endoscopic resection to preserve the esophagus; otherwise they proceed to standard surgery or chemoradiation per clinical judgment. Key eligibility includes biopsy‑proven ESCC staged T1b–3 N0 M0 with tumor ≤5 cm and occupying less than two‑thirds of the luminal circumference, age 18–80, ECOG 0–1, and no prior antitumor therapy.

Who should consider this trial

Good fit: Ideal candidates are treatment‑naïve adults (18–80) with biopsy‑confirmed ESCC staged T1b–3 N0 M0, tumor ≤5 cm and occupying less than two‑thirds of the lumen, and ECOG performance status 0–1.

Not a fit: Patients with node‑positive or metastatic disease, tumors larger than 5 cm or occupying two‑thirds or more of the lumen, prior antitumor therapy, or poor performance status are unlikely to benefit from this organ‑preserving approach.

Why it matters

Potential benefit: If successful, the approach could allow some patients to avoid esophagectomy and preserve their esophagus with endoscopic removal after tumor shrinkage.

How similar studies have performed: Neoadjuvant chemoimmunotherapy for esophageal cancer has produced promising response rates in recent trials, but using it specifically to enable planned organ‑preserving endoscopic resection is a novel approach with limited prior data.

Eligibility criteria

Cohort A - Potentially resectable ESCC:

Inclusion Criteria：

1. Age range: 18-80 years old;
2. Patients diagnosed with esophageal squamous cell carcinoma (ESCC) through histopathological examination of biopsy tissues from the primary tumor;
3. Patients with potentially resectable esophageal cancer confirmed by imaging and endoscopic examinations (T1b-3, N0, M0, with a tumor size not exceeding 5 cm and occupying less than 2/3 of the luminal circumference); Patients who have not received any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
4. Patients with a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
5. Patients with a preoperative American Society of Anesthesiologists (ASA) physical status classification of I-III;
6. Female patients of reproductive age should have a negative pregnancy test and be willing to use effective contraceptive methods during the study period;
7. Patients who have signed the informed consent form.

Exclusion Criteria:

1. Patients with potential tracheoesophageal fistula or aortoesophageal fistula;
2. Patients with severe malnutrition or requiring tube feeding;
3. Patients with other malignancies that have not been cured within the past 2 years (except for cured basal cell carcinoma of the skin and cured carcinoma in situ of the cervix);
4. Patients with active autoimmune diseases or a history of autoimmune diseases or symptoms that require systemic corticosteroid treatment or anti-autoimmune drug therapy;
5. Immunocompromised patients, or patients who are still receiving systemic steroids (prednisone \> 10 mg/day or equivalent) or other forms of immunosuppressive therapy within 7 days before the first dose of neoadjuvant therapy in this study;
6. Patients with active infections requiring systemic treatment within 7 days before the first neoadjuvant therapy in this study;
7. Patients with a history of allogeneic organ or stem cell transplantation;
8. Patients with allergies to drugs or related components involved in this study;
9. Patients who are currently participating in any other clinical study.

Cohort B - Surgery-contraindicated ESCC:

Inclusion Criteria:

1. Individuals aged above 18 years;
2. Patients diagnosed with esophageal squamous cell carcinoma through histopathological examination of biopsy tissues from the primary tumor;
3. Patients with esophageal cancer deemed as surgically contraindicated (including those with cervical esophageal cancer, surgical contraindications, those who refuse surgery, or those considered high-risk for esophagectomy, defined as having at least one of the following characteristics: (1) age over 75 years, (2) Charlson comorbidity index \>= 2, (3) presence of moderate lung dysfunction, (4) malnutrition (with a body mass index below 18 kg/m\^2)), with a clinical staging of cT1b-3N0M0, a tumor size not exceeding 5 cm, and occupying less than 2/3 of the luminal circumference;
4. Patients who have not undergone any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
5. Female patients of reproductive age should have a negative pregnancy test and be willing to adopt effective contraceptive measures during the study period;
6. Patients who have signed the informed consent form.

Exclusion Criteria:

1. Patients with allergies to the drugs or related components involved in this study;
2. Patients who are currently participating in any other clinical study.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Zhongshan Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Li-Yun Ma, MD

Conditions Esophageal Squamous Cell Carcinoma; neoadjuvant, chemoimmunotherapy, tislelizumab, carboplatin, nab-paclitaxel, endoscopic submucosal dissection/ESD