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

March 19, 2026 updated by: Changhai Hospital

A Phase II Clinical Study of Neoadjuvant Therapy With Epacadostat, Lenvatinib, and Chemotherapy in Surgically Resectable Esophageal Cancer

This is a single-arm, exploratory clinical study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a single-arm, single-center, prospective clinical trial. A total of 33 subjects are planned to be enrolled. The study consists of a screening period, a treatment period, and a post-treatment follow-up period. After providing signed informed consent and meeting eligibility criteria, subjects will receive neoadjuvant therapy with epacadostat, tovorafenib, lenvatinib, cisplatin/carboplatin, and nab-paclitaxel. Treatment will be administered in 3-week cycles, with a total of 3 preoperative cycles (lenvatinib will be discontinued in the third cycle).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    1. Neck ultrasound and contrast-enhanced chest/abdominal CT.
    2. Ultrasound-guided lymph node biopsy or PET/CT if clinical suspicion or neck ultrasound suggests cervical lymph node metastasis.
    3. Abdominal non-contrast and contrast-enhanced MRI or PET/CT to confirm diagnosis if CT suggests liver metastasis.
    4. Bone scan if necessary in case of systemic bone pain symptoms.
    5. 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):

    1）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.
  • Subjects must voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

  • 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.
  • Any other condition deemed by the investigator as inappropriate for inclusion in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Iparomlimab and Tuvonralimab + Lenvatinib + Cisplatin/Carboplatin + Nab-paclitaxel

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

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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Pathological Complete Response, pCR
Time Frame: Periprocedural
Periprocedural

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to 2 years
Up to 2 years
Major Pathologic Response（MPR）
Time Frame: Periprocedural
In the tumor bed of the surgical resection specimen, necrotic or regressive tumor tissue ≥90 %.
Periprocedural
objective response rate (ORR)
Time Frame: Up to 2 years
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Changhai Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 6, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 24, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHEC2025-497

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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