Cadonilimab with paclitaxel micelles and cisplatin before surgery for locally advanced esophageal squamous cancer

A Clinical Study on the Efficacy and Safety of Paclitaxel Polymeric Micelles for Injection and Cisplatin Combined With Cadonilimab as a Neoadjuvant Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-Arm, Single-Center, Prospective Clinical Trial (POINTS Trial)

This trial will test whether giving cadonilimab together with paclitaxel polymeric micelles and cisplatin before surgery helps people with locally advanced esophageal squamous cell carcinoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Cadonilimab
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06356688 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, interventional neoadjuvant trial at the First Affiliated Hospital of Nanjing Medical University testing the combination of cadonilimab (a PD-1/CTLA-4 bispecific antibody) with paclitaxel polymeric micelles and cisplatin. Eligible patients receive 2–4 cycles of the combined therapy before planned surgical resection. Key outcomes include pathologic complete response (pCR) rates, objective response rate (ORR), major pathologic response (MPR), R0 resection rate, 2-year overall and progression-free survival, and safety. The trial enrolls adults with resectable or potentially resectable locally advanced thoracic esophageal squamous cell carcinoma and adequate organ function.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 years old with pathologically confirmed thoracic esophageal squamous cell carcinoma that is locally advanced but resectable or potentially resectable (cT2-4aN+ or cT3-4aN0, M0, stage II–IVA), ECOG 0–1, no prior anti‑tumor therapy, and adequate organ and cardiac function.

Not a fit: Patients with distant metastases, prior chemotherapy/radiation/immunotherapy, poor organ or cardiac function, unresectable disease, or ECOG performance status >1 are unlikely to benefit from this neoadjuvant approach.

Why it matters

Potential benefit: If successful, this approach could increase complete tumor disappearance before surgery and improve the chances of a curative operation and longer survival.

How similar studies have performed: Neoadjuvant combinations of immune checkpoint inhibitors with chemotherapy have shown promising pCR rates in esophageal squamous cell carcinoma, but cadonilimab as a PD‑1/CTLA‑4 bispecific agent remains less tested in large randomized neoadjuvant trials.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years, ≤75 years, gender is not limited;
2. Squamous esophageal cancer of thoracic segment confirmed by pathology;
3. Locally advanced patients with no distant metastasis by imaging, resectable or potentially resectable after discussion among oncology, esophageal surgery, and imaging, and clinical stage cT2-4aN+ or cT3-4aN0, M0, stage II, III, or IVA (AJCC 8th edition cTNM staging);
4. ECOG PS score of 0-1;
5. No previous antitumor treatment such as radiotherapy, chemotherapy and immunotherapy;
6. Expected survival \> 6 months;
7. Adequate baseline organ function: (i) WBC ≥3×10\^9/L, ANC ≥1.5×10\^9/L, PLT ≥100×10\^9/L, Hb ≥9g/dL; (ii) Liver function: TBIL ≤2ULN, AST ≤2.5ULN, ALT ≤2.5ULN; (iii) Renal function: cCr\>40 ml/min, Cr≤1.5 ULN; (iv) Cardiac function: no cardiac disease or coronary artery disease. Cardiac function: no heart disease or coronary heart disease, patients with cardiac function grade 1-2;
8. Hypertensive patients applying antihypertensive drugs to control blood pressure within the normal range;
9. Diabetic patients with fasting blood glucose controlled at ≤8mmol/L by hypoglycemic drug treatment;
10. No other serious diseases (such as autoimmune diseases, immunodeficiency, organ transplantation, or other diseases that require continuous hormone therapy) that conflict with this protocol;
11. No history of other malignant tumors;
12. The patient agrees to participate in this clinical study and signs the Informed Consent Form.

Exclusion Criteria:

1. Patients who have previously received anti-tumor therapy (including chemotherapy, radiotherapy, surgery or immunotherapy, etc.);
2. Combination of other incurable malignant tumors (except cured non-malignant skin tumors, cervical cancer in situ, and prostate cancer);
3. Patient has or anticipates a significant risk of esophageal perforation, fistula, and hemorrhage;
4. Active autoimmune or immunodeficiency disease, use of immunosuppressants prior to enrollment, and use of immunosuppressant dosage ≥10 mg/day of oral prednisone for more than 2 weeks;
5. Clinically significant cardiovascular disease including, but not limited to, severe acute myocardial infarction, unstable or severe angina pectoris, coronary artery bypass grafting surgery, congestive heart failure, ventricular arrhythmia requiring medical intervention, left ventricular ejection fraction \<50%, or other anticipated inability to tolerate chemoradiotherapy in the 6 months prior to enrollment;
6. Severe allergies;
7. Pregnant or lactating women;
8. Severe mental disorders;
9. Presence of CTC grade ≥3 peripheral nerve disease;
10. Abnormal coagulation function (PT \> 16s, APTT \> 53s, TT \> 21s, Fib \< 1.5g/L), bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
11. Presence of severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, severe impairment of lung function, or active tuberculosis within 1 year;
12. Presence of active hepatitis B or C;
13. Any other condition that the investigator evaluates to be ineligible for enrollment.

Where this trial is running

Nanjing, Jiangsu

• the First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Jing Sun

Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma, Neoadjuvant Therapy, cadonilimab, neoadjuvant therapy, esophageal squamous cell carcinoma, Paclitaxel Polymeric Micelles for Injection