Candonilimab (AK104) Plus Preoperative Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

A Phase II Study of Candonilimab (AK104) Combined With Preoperative Chemotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

This is a prospective, single-arm, open-label，multi-center, phase II study, aiming to evaluate the efficacy and safety of AK104 combined with preoperative chemotherapy in patients with locally advanced ESCC.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: AK104, nab-paclitaxel, carboplatin

Detailed Description

Eligible patients first receive AK104 (10mg/kg, iv, Q2W) for one cycle in the induction period, and then patients receive AK104 (10mg/kg, iv, Q3W) combined with nab-paclitaxel (130mg/m2 ivgtt d1，d8, Q3W) and carboplatin ((AUC=5) d1，Q3W) for 2 cycles. After neoadjuvant therapy of 3 cycles, patient will undergo preoperative evaluation. For patients who can be performed for R0 surgery, surgery wil be performed in 4 to 6 weeks. Patients who do not achieve Pathological complete response (pCR) will receive AK104 (10mg/kg, iv, Q3W) as adjuvant therapy until disease progression or intolerable toxicity for up to 12 months. Patients who achieve pCR after surgery will be enrolled in observational follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Feng Wang; Phone Number: 13938244776; Email: fengw010@163.com

Study Locations

• China
  • Henan
    • Anyang, Henan, China, 450052
      • Anyang Cancer Hospital
      • Contact: Anlin Hao
    • Zhengzhou, Henan, China, 450052
      • Feng Wang
      • Contact: Feng Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily signing a written informed consent form;
2. Males or females aged ≥ 18 to ≤ 70 years;
3. ECOG score 0-1;
4. Pathologically diagnosed thoracic esophageal squamous cell carcinoma;
5. No distant metastasis after imaging examination, and esophageal cancer can be resected or potentially resectable with stage cT1b-cT2N+M0 or cT3-cT4a anyN M0 or cT2N0M0 high-risk (lymphovascular invasion or tumor ≥3 cm or hypo-differentiation) (AJCC 8th edition cTNM stage);
6. Not received prior antitumor therapy (surgery, radiotherapy, chemotherapy, immunotherapy, etc. for esophageal cancer);
7. Life expectancy is greater than 6 months;
8. At least one measurable tumor lesion per RECIST v1.1;
9. Major organ functions are adequate;

Exclusion Criteria:

1. Patient has received previous antitumor therapy (chemotherapy, radiation, surgery or immunotherapy);
2. Cervical or thoracic esophageal cancer is < 5 cm from the cricopharyngeal muscle;
3. Patients are or are expected to be at significant risk of esophageal perforation, fistula, and major bleeding;
4. Imaging during the screening period showed that the tumor surrounded or invaded important blood vessels or organs (such as the heart and pericardium, trachea, aorta, superior vena cava, etc.) or there was obvious necrosis or cavity, and the investigator determined that entering the study would cause bleeding risk; participants at risk of developing oesophageal or oesophageal fistula;
5. Patients with a history of other malignant diseases in the last 5 years，unless complete resolution or no additional treatment is required (exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer or prostate, cervix, or breast carcinoma in situ)；
6. Pregnant or nursing women；
7. Patients with known or suspected active autoimmune disease;
8. Patients with a history of myocarditis, cardiomyopathy, malignant arrhythmias;
9. Other patients are not eligible for enrollment assessed by investigators;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 plus nab-paclitaxel and carboplatin; In the induction period, AK104 (10mg/kg, iv, Q2W) is given for one cycle; and then AK104 (10mg/kg, iv, Q3W) is combined with nab-paclitaxel (130mg/m2 ivgtt d1，d8, Q3W) and carboplatin ((AUC=5) d1，Q3W) for 2 cycles; After R0 surgery, AK104 (10mg/kg, iv, Q3W) is given as adjuvant therapy for up to 12 months for those who do not achieve pCR.	Drug: AK104, nab-paclitaxel, carboplatin; AK104 plus nab-paclitaxel and carboplatin as neoadjuvant therapy，and AK104 as adjuvant therapy for those who do not achieve pCR; Other Names: Candonilimab，Preoperative Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	Pathological complete response	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR	Major pathologic response	up to 2 years
R0 resection rate	R0 resection rate	up to 2 years
Downstaging rate	Downstaging rate	up to 2 years
DFS	Disease-free survival	up to 2 years
OS	Overall survival	up to 2 years
AE	Adverse event	up to 2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Feng Wang, The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: surgery; preoperative chemotherapy; AK104
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: L2023-K003-002

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