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

NCT07712094 | Not Yet Recruiting Phase 2

• 1 other identifier: AK112-IIT-C-N-0010
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Neuroendocrine Cancer

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  PFS is defined as the time from date of treatment start to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1

  Up to 2 years

Secondary Outcomes (5)

• objective response rate (ORR)

  Up to 2 years

• disease control rate (DCR)

  Up to 2 years

• duration of response (DOR)

  Up to 2 years

• overall survival (OS)

  Up to 2 years

• The number of subjects experiencing adverse events (AEs)

  From the time of treatment start through 90 days following termination of treatment with investigational product

Study Arms (2)

NEC

EXPERIMENTAL

Drug: AK112; Drug: Irinotecan; Drug: Cisplatin

NEC with liver metastases

EXPERIMENTAL

Drug: AK112; Drug: Irinotecan; Drug: Cisplatin; Procedure: TACE

Interventions

Irinotecan DRUG

Combination treatment period (4-6 cycles): Irinotecan: 65 mg/m2, intravenous infusion, administered on days 1 and 8, repeated every 3 weeks

NEC; NEC with liver metastases

AK112 DRUG

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

NEC; NEC with liver metastases

Cisplatin DRUG

Combination treatment period (4-6 cycles): Cisplatin: 30 mg/m2, intravenous infusion, administered on days 1 and 8, repeated every 3 weeks

NEC; NEC with liver metastases

TACE PROCEDURE

Combination treatment period: TACE with epirubicin, 30-40 mg, every 3 weeks or every 6 weeks. The total treatment cycle is determined as needed.

NEC with liver metastases

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (8)

Baotou Cancer Hospital

Baotou, Inner Mongolia, China

Location

The First People's Hospital of Horqin District, Tongliao City

Tongliao, Inner Mongolia, China

Location

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Location

Tianjin First Central Hospital

Tianjin, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, China

Location

Tianjin Medical University General Hospital

Tianjin, China

Location

Tianjin People's Hospital

Tianjin, China

Location

Tianjin Third Central Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

Irinotecan; Cisplatin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Rui Liu, Dr.

CONTACT

86+022-23340123; liurui9003@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study was a parallel double cohort design. Cohort 1 included patients with metastatic digestive system neuroendocrine cancer who had not received systemic treatment. They received AK112 combined with IP chemotherapy, followed by maintenance with AK112 monotherapy. Cohort 2 included patients with liver metastatic digestive system neuroendocrine cancer who had not received systemic treatment. They received AK112 combined with IP chemotherapy, along with TACE, and then maintained with AK112 monotherapy. The treatment continued until the subjects experienced disease progression, intolerable toxicity, the decision of the investigator, the subject withdrawing informed consent, death, or other reasons stipulated in the protocol.

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 17, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): February 27, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: July 17, 2026

Record last verified: 2026-07

Locations

CN (8)