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

Sponsor

The First Affiliated Hospital of Zhengzhou University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05896787

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

22.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Drug: AK104, nab-paclitaxel, carboplatin	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

pCR [up to 2 years]
Pathological complete response

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntarily signing a written informed consent form;
Males or females aged ≥ 18 to ≤ 70 years;
ECOG score 0-1;
Pathologically diagnosed thoracic esophageal squamous cell carcinoma;
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);
Not received prior antitumor therapy (surgery, radiotherapy, chemotherapy, immunotherapy, etc. for esophageal cancer);
Life expectancy is greater than 6 months;
At least one measurable tumor lesion per RECIST v1.1;
Major organ functions are adequate;

Exclusion Criteria:

Patient has received previous antitumor therapy (chemotherapy, radiation, surgery or immunotherapy);
Cervical or thoracic esophageal cancer is < 5 cm from the cricopharyngeal muscle;
Patients are or are expected to be at significant risk of esophageal perforation, fistula, and major bleeding;
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;
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)；
Pregnant or nursing women；
Patients with known or suspected active autoimmune disease;
Patients with a history of myocarditis, cardiomyopathy, malignant arrhythmias;
Other patients are not eligible for enrollment assessed by investigators;