A Prospective, Multicenter, Phase Ib/II Trial of Ivonescimab (AK112) Combined With Albumin-Paclitaxel and Cisplatin as Neoadjuvant Therapy for ESCC

NCT07385001 | Recruiting Phase 1

• 1 other identifier: K202506-23
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

A Prospective, Multicenter, Phase Ib/II Trial of Ivonescimab (AK112) Combined with Albumin-Paclitaxel and Cisplatin as Neoadjuvant Therapy for Resectable, Locally Advanced Esophageal Squamous Cell Carcinoma

Conditions

Esophageal Squamous Cell Carcinoma; Ivonescimab; Neoadjuvant

Keywords

Neoadjuvant; Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (5)

• DLT

  Dose-limiting toxicity

  1 year

• Incidence and Severity of Adverse Events

  1 year

• MTD

  Maximum tolerated dose

  1 year

• RP2D

  Recommended Phase II Dose

  1 year

• Major Pathologic Response(MPR)

  Defined as a residual viable tumor percentage (RVT%) ≤ 10%

  up to 2 years

Secondary Outcomes (4)

• Objective response rate (ORR) by RECIST v1.1

  Up to 2 years

• Event-Free Survival (EFS)

  Up to 2 years

• Total survival time (OS)

  Up to 2 years

• Adverse Events (AE), Serious Adverse Events (SAE), and Immune-Related Adverse Events (irAE): Incidence and Severity

  From the time of informed consent signed through 90 days after the last dose of study drug

Study Arms (3)

Phase 1b-Cohort 1

EXPERIMENTAL

Subjects will receive AK112 via intravenously (IV) Q3W

Drug: AK112

Phase 1b-Cohort 2

EXPERIMENTAL

Subjects will receive AK112 via intravenously (IV) Q3W

Drug: AK112

Phase 2a

EXPERIMENTAL

Subjects will receive AK112 via intravenously (IV) Q3W+Albumin-paclitaxel 130 mg/m²,via intravenously (IV); carboplatin with an area under the curve (AUC) of 5 mg/ml/min, via intravenously (IV) Q3W, for a total of 3 cycles

Drug: AK112 + Neoadjuvant chemotherapy

Interventions

AK112 DRUG

Cohort 1- AK112 10 mg/kg, every 3 weeks (Q3W), administered intravenously on day 1. Treatment will begin with the first patient. If the first patient does not experience any treatment-related safety issues, at least 24 hours will pass before the next 2 or 3 patients are treated.The dosing regimen and interval will remain unchanged for all patients

Phase 1b-Cohort 1

AK112 + Neoadjuvant chemotherapy DRUG

Neoadjuvant chemotherapy: Albumin-paclitaxel 130 mg/m², intravenous infusion on days 1 and 8, every 3 weeks (Q3W), total of 3 cycles Carboplatin with an area under the curve (AUC) of 5 mg/ml/min, intravenous infusion on day 1, every 3 weeks (Q3W), total of 3 cycles AK112: Based on the data collected during the dose-escalation phase 1b

Phase 2a

Eligibility Criteria

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

You may qualify if:

• Informed Consent: Written informed consent must be obtained before any study-related procedures are initiated.
• Age and Gender: Participants must be between 18 and 75 years of age, inclusive of both 18 and 75 years, and may be either male or female.
• Diagnosis and Stage: Participants must be histologically confirmed to have resectable, locally advanced esophageal squamous cell carcinoma (ESCC) with the following criteria:-T1 N1-N3 M0 or T2-T4a N0-N3 M0 (with T2 ≥ 2 cm or poorly differentiated).
• Lymph Node Status: No suspicious lymph nodes in the neck region (excluding lymph nodes in the upper thoracic esophageal area) as per neck ultrasound or enhanced CT scan; no evidence of systemic metastasis on imaging.
• R0 Resectability: The participant is expected to achieve R0 resection.
• Measurable Lesion: At least one measurable tumor lesion must be present.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected Survival: The participant is expected to have a survival duration of at least 3 months.
• Thyroid Function: Normal thyroid function is defined as a thyroid-stimulating hormone (TSH) level within the normal range. Participants with baseline TSH levels outside the normal range may still be eligible if total T3 (or free T3) and free T4 levels are within the normal range.
• Organ Function: Laboratory results must meet the following criteria:
• Hematology (no blood transfusion or blood component or granulocyte colony-stimulating factor treatment within 14 days): Neutrophil count (NEU) ≥ 1.5 × 10⁹/L (1,500/mm³); Platelet count (PLT) ≥ 100 × 10⁹/L (100,000/mm³); Hemoglobin ≥ 90 g/L.
• Liver: Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN); or for participants with TBil \< 1.5 × ULN, direct bilirubin must be within the normal range; Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Renal: Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).
• Coagulation: International Normalized Ratio (INR) ≤ 1.5; Prothrombin time (PT) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50%.

You may not qualify if:

• History of Other Malignancies: Participants who have had any other malignancy within 5 years prior to enrollment are excluded, except for those with localized or in situ malignancies such as basal or squamous cell carcinoma, superficial bladder cancer, cervical or breast intraepithelial neoplasia, or other conditions that are considered curable with local therapy.
• Prior Treatment with PD-1/PD-L1 Inhibitors or Other Immune-Modulating Drugs: Participants who have previously received treatment with PD-1/PD-L1 inhibitors or other drugs targeting T-cell receptors (e.g., CTLA-4, OX-40) or anti-angiogenic agents (e.g., bevacizumab, endostar) are excluded.
• Systemic Non-Specific Immune Modulation: Participants who have received systemic non-specific immune-modulating therapy (e.g., interleukins, interferons, thymopentin) within 2 weeks prior to the first dose of study drug, or who have used traditional Chinese medicine or herbal preparations with anti-tumor indications within 2 weeks prior to the first dose, are excluded.
• Active Autoimmune Disease Requiring Systemic Treatment: Participants with active autoimmune diseases requiring systemic treatment (e.g., using disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressants) are excluded. Substitutive treatments (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered as systemic treatment.
• Brainstem, Meningeal, or Spinal Metastasis or Compression: Participants with brainstem, meningeal, or spinal metastasis, or with evidence of compression, are excluded.
• Significant Pleural, Pericardial, or Peritoneal Effusion: Participants with clinically significant pleural, pericardial, or peritoneal effusions requiring diuretic therapy and/or repeated drainage are excluded.
• Gastrointestinal Obstruction or Complications Within 6 Months of First Dose: Participants with a history of clinically significant gastrointestinal obstruction, perforation, intra-abdominal abscess, or fistula formation within 6 months prior to the first dose of study drug are excluded.
• Active Inflammatory Gastrointestinal Diseases: Participants with active inflammatory gastrointestinal diseases (e.g., Crohn's disease, ulcerative colitis, radiation enteritis, hemorrhagic enteritis, chronic diarrhea) are excluded.
• Tumor Encircling Major Vessels or Severe Necrosis/Hemorrhage: Participants with imaging findings showing tumor encircling major vessels, significant necrosis, or cavitation, and whose researchers determine that entry into the study would pose a bleeding risk, are excluded.
• Interstitial Lung Disease ≥ Grade 2: Participants with interstitial lung disease ≥ Grade 2 are excluded.
• Severe Cardiovascular Disease:
• Uncontrolled hypertension or pulmonary hypertension; Unstable angina pectoris, myocardial infarction within 6 months prior to the first dose of study drug, coronary artery bypass grafting, or stent implantation; Chronic heart failure with NYHA functional class ≥ 2; Left ventricular ejection fraction (LVEF) \< 50%;
• Severe arrhythmias requiring drug treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia), such as QTcF \> 450 msec in males or \> 470 msec in females, complete left bundle branch block, or third-degree heart block; Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 4 weeks prior to the first dose of study drug.
• Severe Infection Within 4 Weeks Prior to First Dose: Participants with a history of severe infection (e.g., sepsis, bacteremia, or severe pneumonia) within 4 weeks prior to the first dose of study drug, or who have received systemic antimicrobial therapy for an active infection (excluding antiviral treatment for hepatitis B or C) within 2 weeks prior to the first dose, are excluded.
• Active Tuberculosis or Syphilis: Participants with known active tuberculosis (TB) or syphilis are excluded. Suspected TB cases must be ruled out with clinical evaluation.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

Tangdu Hospitial

Xi'an, Shannxi, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

Xiaolong Yan

CONTACT

+86 15991269383; yanxiaolong@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: February 3, 2026
• Study Start: January 28, 2026
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): January 28, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

CN (1)