Neoadjuvant Therapy With Iparomlimab and Tuvonralimab, Lenvatinib and Chemotherapy in Resectable ESCC

NCT07490002 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CHEC2025-497
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, exploratory clinical study.

Conditions

Esophageal Squamous Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response, pCR

  Periprocedural

Secondary Outcomes (3)

• objective response rate (ORR)

  Up to 2 years

• Major Pathologic Response（MPR）

  Periprocedural

• Progression-Free Survival (PFS)

  Up to 2 years

Study Arms (1)

Iparomlimab and Tuvonralimab + Lenvatinib + Cisplatin/Carboplatin + Nab-paclitaxel

EXPERIMENTAL

Iparomlimab and Tuvonralimab: 5 mg/kg, Day 1; Lenvatinib: 8 mg, orally, once daily (QD), Day 1-14; Note: Lenvatinib will be discontinued starting from Cycle 3. Cisplatin: 75 mg/m², or Carboplatin: AUC 5, intravenously (IV), Day 1; Nab-paclitaxel: 125 mg/m², Day 1 and Day 8; The cycle repeats every 3 weeks.

Drug: Iparomlimab and Tuvonralimab+Lenvatinib + Cisplatin/Carboplatin + Nab-paclitaxel

Interventions

Iparomlimab and Tuvonralimab+Lenvatinib + Cisplatin/Carboplatin + Nab-paclitaxel DRUG

Iparomlimab and Tuvonralimab: 5 mg/kg, Day 1; Lenvatinib: 8 mg, orally, once daily (QD), Day 1-14; Note: Lenvatinib will be discontinued starting from Cycle 3. Cisplatin: 75 mg/m², or Carboplatin: AUC 5, intravenously (IV), Day 1; Nab-paclitaxel: 125 mg/m², Day 1 and Day 8; The cycle repeats every 3 weeks.

Iparomlimab and Tuvonralimab + Lenvatinib + Cisplatin/Carboplatin + Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: no restriction; Age: 18-75 years.
• Histologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma.
• Clinical stage II-IVa (T2-4aN+M0) according to the AJCC 8th edition, and assessed as resectable by a multidisciplinary team (MDT).
• Complete imaging work-up shows no evidence of distant metastasis:
• Neck ultrasound and contrast-enhanced chest/abdominal CT.
• Ultrasound-guided lymph node biopsy or PET/CT if clinical suspicion or neck ultrasound suggests cervical lymph node metastasis.
• Abdominal non-contrast and contrast-enhanced MRI or PET/CT to confirm diagnosis if CT suggests liver metastasis.
• Bone scan if necessary in case of systemic bone pain symptoms.
• Endoscopic ultrasound for accurate staging.
• No prior antitumor therapy received (including radiotherapy, chemotherapy, targeted therapy, immunotherapy, or traditional Chinese medicine).
• ECOG Performance Status score: 0-1.
• Adequate organ function, meeting the following laboratory criteria (no blood transfusion, granulocyte colony-stimulating factor \[G-CSF\], or corrective medication within 14 days prior to treatment):
• ）Hemoglobin (Hb) ≥90 g/L. 2）Absolute neutrophil count (ANC) ≥1.5×10⁹/L. 3）Platelet count (PLT) ≥100×10⁹/L. 4）Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN). 5）Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. 6）Serum creatinine clearance (CrCl) ≥50 mL/min (calculated by Cockcroft-Gault formula). 7）Coagulation: International normalized ratio (INR) ≤1.5 × ULN, activated partial thromboplastin time (APTT) ≤1.5 × ULN. 8）Proteinuria \< 2+ (if ≥ 2+, a 24-hour urine protein quantification must be performed; patients are eligible if the result is ≤1 g). 9）Left ventricular ejection fraction (LVEF) ≥50%.
• No surgical contraindications.
• The subject agrees to use effective contraception from the signing of the informed consent form until 180 days after the last dose. Female subjects of childbearing potential must not be pregnant or breastfeeding.

You may not qualify if:

• Known history of hypersensitivity to macromolecular protein preparations. Contraindications or allergies to any component of epaplimut-pembrolizumab.
• Other anti-tumor therapies (chemotherapy, radiotherapy, surgery, immunotherapy, biological therapy, chemoembolization, anti-tumor traditional Chinese herbal medicine).
• Radiographic diagnosis indicating distant metastasis of the tumor.
• History of allogeneic tissue/solid organ transplantation.
• Within 2 weeks prior to the first dose, presence of a condition requiring systemic corticosteroid (\>10 mg daily prednisone or equivalent) or other immunosuppressive medication (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-α inhibitors, etc.). Topical, nasal spray, and inhaled corticosteroids are permitted. Prophylactic use of systemic corticosteroids for contrast agent allergy is allowed.
• Active or potentially recurrent autoimmune diseases, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy; hypothyroidism due to autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; type I diabetes requiring only stable-dose insulin replacement therapy.
• Other active malignancies within the past 5 years, except for cured localized cancers (e.g., basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast) and breast cancer without recurrence for more than 3 years after radical surgery.
• History of interstitial lung disease and/or pneumonitis or pulmonary hypertension.
• Poorly controlled ascites, pericardial effusion, or pleural effusion requiring repeated drainage.
• Poorly controlled hypertension (systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg) and diabetes despite standard treatment, or uncontrolled or symptomatic arrhythmia.
• Thromboembolic events within 6 months prior to the start of study treatment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction) or pulmonary embolism.
• Myocardial infarction within the past 12 months, severe/unstable angina, or symptomatic congestive heart failure (NYHA class III or IV).
• Participation in other clinical trials within 60 days prior to or during the treatment period.
• Known active infection with HIV, HBV, or HCV.
• Major surgery (excluding needle biopsy) within 4 weeks prior to the first dose without full recovery.

Sponsors & Collaborators

• Changhai Hospital: lead

MeSH Terms

Interventions

Cisplatin; Carboplatin; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

Xianbao Zhan

CONTACT

862131162338; zhanxianbao@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: March 24, 2026
• Study Start: April 6, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2030
• Last Updated: March 24, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share