AK112 Combination Therapy as First Line Treatment for Metastatic Digestive System Neuroendocrine Cancer

Official title

A Prospective, Parallel, Double-cohort, Multicenter Phase II Clinical Study of Ivonescimab (AK112) Combined With IP Chemotherapy ± TACE for First-line Treatment of Metastatic Digestive System Neuroendocrine Cancer

Overview

This study is a single prospective, parallel, double-cohort, multicenter phase II clinical trial, aiming to evaluate the efficacy and safety of ivonescimab (AK112) combined with IP chemotherapy ± TACE in the first-line treatment of metastatic digestive system neuroendocrine cancer.

Interventions

• Drug AK112
  Combination treatment period (4-6 cycles): AK112: 20mg/kg, intravenous infusion, administered on day 1, repeated every 3 weeks Maintenance treatment period: AK112: 20mg/kg, intravenous infusion, administered on day 1, repeated every 3 weeks
• Drug Irinotecan
  Combination treatment period (4-6 cycles): Irinotecan: 65 mg/m2, intravenous infusion, administered on days 1 and 8, repeated every 3 weeks
• Drug Cisplatin
  Combination treatment period (4-6 cycles): Cisplatin: 30 mg/m2, intravenous infusion, administered on days 1 and 8, repeated every 3 weeks
• Procedure TACE
  Combination treatment period: TACE with epirubicin, 30-40 mg, every 3 weeks or every 6 weeks. The total treatment cycle is determined as needed.

Primary outcome measures

• progression-free survival (PFS) [Time frame: Up to 2 years]

Secondary outcome measures (5)

• objective response rate (ORR) [Time frame: Up to 2 years]
• disease control rate (DCR) [Time frame: Up to 2 years]
• duration of response (DOR) [Time frame: Up to 2 years]
• overall survival (OS) [Time frame: Up to 2 years]
• The number of subjects experiencing adverse events (AEs) [Time frame: From the time of treatment start through 90 days following termination of treatment with investigational product]

Eligibility criteria

Inclusion criteria

• Age: 18 - 75 years old;
• Metastatic digestive system neuroendocrine carcinoma (NEC) confirmed by tissue or cytological examination;
• For cohort 2 only: Liver metastasis, suitable for TACE;
• No previous systemic treatment; For patients who received adjuvant therapy, disease recurrence and metastasis more than 6 months after the last treatment can be regarded as first-line treatment;
• Clear measurable lesions meeting the requirements of RECIST (1.1); If the lesion that received previous local treatment (radiation, ablation, vascular intervention, etc.) is the only lesion, there must be clear imaging evidence of disease progression for this lesion;
• ECOG score of 0 or 1;
• Expected survival ≥ 12 weeks;
• Basic normal functions of major organs and bone marrow;
• Male or female patients with reproductive capacity voluntarily use effective contraceptive methods during the study period and within 6 months after the last study medication, such as double barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered to have reproductive capacity, unless the female patient has naturally menopause, artificial menopause or sterilization (such as hysterectomy, bilateral ovary removal or radiotherapy of the ovaries, etc.).
• Have fully understood this study, voluntarily participated, and signed the informed consent form.

Exclusion criteria

• Within the past 5 years, have been diagnosed with other malignant tumors (excluding carcinoma in situ, basal cell carcinoma, etc.);
• Known to be allergic to any component of any study drug; have a history of severe hypersensitivity reaction to other monoclonal antibodies;
• Within 4 weeks before enrollment, have received approved or investigational systemic anti-tumor treatment, including: photodynamic therapy, chemotherapy, radical radiotherapy, ablation, local radiotherapy (allowing for palliative radiotherapy for bone metastases at least 2 weeks before the study drug treatment), biological immunotherapy, targeted therapy, etc.;
• Within 4 weeks before enrollment, have participated in other domestic clinical trials of drugs that have not been approved or are not yet on the market and have received corresponding trial drug treatment;
• Within 4 weeks before enrollment, have received any surgery or invasive treatment or operation (except for intravenous catheterization, puncture drainage, etc.);
• The patient currently has active ulcers in the stomach and duodenum, ulcerative colitis and other digestive tract diseases or active bleeding from the unresected tumor, or conditions that the investigator deems may cause gastrointestinal bleeding or perforation;
• Within 3 months before enrollment, have obvious evidence or history of bleeding (more than 30 mL of bleeding within 3 months, hematemesis, black stool, bloody stool), hemoptysis (more than 5 mL of fresh blood within 4 weeks), or have had a thromboembolic event within 12 months (including stroke events and/or transient ischemic attacks);
• Have significant clinical cardiovascular diseases, including but not limited to acute myocardial infarction within 6 months before enrollment, severe/unstable angina pectoris or coronary artery bypass surgery; New York Heart Association (NYHA) class > 2 for congestive heart failure; Drug treatment for ventricular arrhythmias; Electrocardiogram (ECG) showing QTc interval ≥ 480 milliseconds;
• Unstable brain parenchymal metastases, spinal cord metastases or compression, cancerous meningitis or meningitis metastasis;
• Have third space fluid that cannot be controlled by drainage methods (such as large amounts of ascites, pleural effusion, pericardial effusion, etc.), and the subjects need to control the third space fluid through drainage within 14 days before administration;
• Active or uncontrolled severe infection (≥ CTCAE grade 2 infection);
• Known human immunodeficiency virus (HIV) infection; Known significant liver disease history, including viral hepatitis \[must exclude active HBV infection if the HBV DNA is positive (> 1×10\^4 copies/mL or > 2000 IU/ml); known hepatitis C infection (HCV) and HCV RNA positive (> 1×10\^3 copies/mL), or other hepatitis, liver cirrhosis\];
• Known mental illness, drug abuse, alcoholism or drug addiction history.
• Pregnant or lactating women.
• Have any disease, treatment, laboratory test abnormalities in the past or currently, which may confuse the research results, affect the full participation of the subjects in the research, or the participation in the research may not be in the best interests of the subjects.
• Local or systemic diseases not caused by malignant tumors, or secondary diseases or symptoms of tumors, which may lead to higher medical risks and/or uncertainty in survival period evaluation, such as tumor leukemia reaction (white blood cell count > 20×109/L), cachexia manifestations (such as weight loss of more than 10% within 3 months before screening), etc.
• Patients judged by the investigator to be unsuitable to participate in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 8 centers

• Baotou Cancer Hospital — Baotou
• The First People's Hospital of Horqin District, Tongliao City — Tongliao
• Shanxi Bethune Hospital — Taiyuan
• Tianjin First Central Hospital — Tianjin
• Tianjin Medical University Cancer Institute and Hospital — Tianjin
• Tianjin Medical University General Hospital — Tianjin
• Tianjin People's Hospital — Tianjin
• Tianjin Third Central Hospital — Tianjin

Identifiers

NCT: NCT07712094 · AK112-IIT-C-N-0010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗