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

Phase 2

Not yet recruiting

• Conditions: Esophageal Squamous Cell Carcinoma
• Interventions: Drug: AK104, nab-paclitaxel, carboplatin

• Registration Number: NCT05896787
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

Brief Summary

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.

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 Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-06-01
• Study First Submitted QC: 2023-06-01
• Last Update Submitted: 2023-06-01
• Study First Posted: 2023-06-09
• Last Update Posted: 2023-06-09
• Study Start: 2023-08-01
• Primary Completion: 2024-08-01
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AK104 plus nab-paclitaxel and carboplatin	AK104, nab-paclitaxel, 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.

Primary Outcome Measures

Name	Time	Method
pCR	up to 2 years	Pathological complete response

Secondary Outcome Measures

Name	Time	Method
MPR	up to 2 years	Major pathologic response
OS	up to 2 years	Overall survival
R0 resection rate	up to 2 years	R0 resection rate
DFS	up to 2 years	Disease-free survival
Downstaging rate	up to 2 years	Downstaging rate
AE	up to 2 years	Adverse event

Trial Locations

Locations (2)

Anyang Cancer Hospital; 🇨🇳 Anyang, Henan, China

Feng Wang; 🇨🇳 Zhengzhou, Henan, China