Clinical trial NCT05896787: Candonilimab (AK104) Plus Preoperative Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Official title: A Phase II Study of Candonilimab (AK104) Combined With Preoperative Chemotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: AK104
preoperative chemotherapy
surgery
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: pCR
timeFrame: up to 2 years
Secondary outcomes:
measure: MPR
timeFrame: up to 2 years
measure: R0 resection rate
timeFrame: up to 2 years
measure: Downstaging rate
timeFrame: up to 2 years
measure: DFS
timeFrame: up to 2 years
measure: OS
timeFrame: up to 2 years
measure: AE
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Anyang
country: China
facility: Anyang Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Feng Wang
state: Henan
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Feng Wang
role: PRINCIPAL_INVESTIGATOR
References: