A Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin in Biliary Tract Malignancies

A Single-arm Prospective Clinical Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin for the Neoadjuvant Treatment of Biliary Tract Malignancies

Evaluating the efficacy and safety of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of patients with biliary tract malignancies.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Malignancies
• Intervention / Treatment: Drug: Adebrelimab; Drug: Apatinib; Drug: Gemcitabine; Drug: Cisplatin

Detailed Description

Existing immune-combination chemotherapy has shown excellent data in advanced biliary malignancies, so what is the efficacy and safety of this regimen in neoadjuvant therapy? Moreover, the current combination model of immunization combined with anti-angiogenic drugs has become another new direction in the field of solid tumor treatment. Therefore, our group designed a single-arm, prospective clinical study of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of biliary malignancies, aiming at evaluating the efficacy and safety of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of biliary malignancies in patients with a view to bringing longer-term benefits to patients with resectable biliary malignancies.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhibo Zhang; Phone Number: 13960986516; Email: zbzhang_1234@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • The First Affiliated Hospital of Fujian Medical University
      • Contact: Zhang Zhibo, PhD; Phone Number: 008618559853003; Email: wql0211@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age: 18 years old ≤ 75 years old, both male and female.
• 2. Patients with gallbladder cancer or cholangiocarcinoma (intrahepatic or extrahepatic) diagnosed by histologic or cytologic examination.
• 3. high-quality cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) with a diagnosis of surgically resectable high-risk biliary malignancy limited to the liver, bile ducts, and/or regional lymph nodes. (Must meet at least one of the following criteria)
• (1) T-grade ≥ Ib (Ib-IV);
• (2) Single lesion > 5 cm;
• (3) Multifocal tumors or satellite lesions confined to the same hepatic lobe as the primary lesion but still technically resectable;
• (4) Presence of major vascular invasion but still technically resectable;
• (5) Suspected or involved regional lymph nodes (N1);
• (6) No distant extrahepatic disease (M0).
• 4. Patients who have not received previous systemic therapy and who, in the judgment of the physician, have no contraindications to surgery, and the patient agrees to undergo radical surgical treatment.
• 5. At least one measurable lesion (according to the RECIST 1.1 criteria requires that the measurable lesion be ≥10 mm in long diameter on spiral CT scan or ≥15 mm in short diameter in malignant lymph nodes).
• 6. ECOG PS score of 0-1.
• 7. Expected survival ≥ 12 weeks.
• 8. Normal function of major organs and fulfillment of the following criteria:
• (1) Criteria for routine blood tests need to be met: (no blood transfusion within 14 days)
• a. Hemoglobin (HB) ≥ 90g/L;
• b. White blood cell count (WBC) ≥3×109/L;
• c. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
• d. Platelet (PLT) ≥80×109/L.
• (2) Biochemical tests need to meet the following criteria:
• a. Bilirubin (BIL) <1.5 times the upper limit of normal (ULN);
• b. Glutamine aminotransferase (ALT) and glutamine aminotransferase AST <5 ULN;
• c. serum creatinine (Cr) ≤ 1.5 ULN.
• 9. Women of childbearing potential must have a negative pregnancy test (serum) or urine HCG test within 7 days prior to enrollment and be willing to use an appropriate method of contraception for the duration of the trial and for 8 weeks after the last administration of the test drug; in the case of males, they should be surgically sterilized or agree to use an appropriate method of contraception for the duration of the trial and for 8 weeks after the last administration of the test drug.
• 10. Subjects voluntarily enroll in the study, have good compliance, and cooperate with follow-up visits.

Exclusion Criteria:

• 1. Pregnant or lactating women.
• 2. Patients with autoimmune diseases, organ/hematopoietic stem cell transplantation or other malignant tumors (except cured basal cell carcinoma of the skin and cervical carcinoma in situ).
• 3. Patients with impaired consciousness or inability to cooperate with treatment, or patients with combined mental illness.
• 4. Patients who have participated in other clinical trials in the last three months.
• 5. Patients who have received other PD-1, PD-L1, CTLA-4 inhibitors in the past.
• 6. Patients who have undergone major surgery or chemotherapy or other systemic or localized treatments (including but not limited to radiation therapy, ablation therapy, etc.) for the target lesion prior to enrollment.
• 7. Use of interferon or systemic hormone therapy for immunosuppression within 14 days prior to enrollment (dose >10mg/day prednisone or other equipotent hormone).
• 8. Prior hypersensitivity to PD-1, PD-L1, CTLA-4 monoclonal antibody, any component of a chemotherapeutic agent, or other drugs of the same type used in the trial.
• 9. Bleeding from ruptured esophageal (fundus) varices within 1 month prior to treatment.
• 10. Uncorrectable coagulation dysfunction and serious blood abnormalities with severe bleeding tendency. Platelet count <50×109/L and severe coagulation abnormality cannot withstand surgery (anticoagulation therapy and/or anticoagulant application should be discontinued for more than 1 week before radiation therapy).
• 11. Intractable large amount of ascites and pleural fluid, malaise.
• 12. Severe liver, kidney, heart, lung, brain and other major organ failure.
• 13. Suffer from high blood pressure which cannot be reduced to normal range by antihypertensive drugs (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• 14. Previous severe cardiovascular disease, including but not limited to the following: myocardial ischemia or myocardial infarction of grade II or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men and ≥470 ms for women); cardiac insufficiency of grades Ⅲ to Ⅳ according to the NYHA standard or cardiac ultrasound suggesting that the left ventricular ejection fraction (LVEF) is <50%.
• 15. Patients with positive urine protein (urine protein test of 2+ or more, or 24-hour urine protein quantification >1.0g).
• 16. Inability to swallow tablets, malabsorption syndrome, or any condition that interferes with gastrointestinal absorption.
• 17. Patients with other serious concomitant conditions that, in the judgment of the investigator, jeopardize patient safety or interfere with the patient's ability to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin	Drug: Adebrelimab; Adebrelimab: 1200mg or 20mg/kg, iv, D1, Q3W; Other Names: SHR-1316; Drug: Apatinib; Apatinib: 250 mg, po, QD, Q3W; Drug: Gemcitabine; Gemcitabine: 1000 mg/m2, iv, 30min, D1, D8, Q3W; Drug: Cisplatin; Cisplatin: 25 mg/m2, iv, 30min, D1, D8, Q3W; Injection sequence: adebelizumab → gemcitabine → cisplatin (sequential interval of at least 30 min), 3 cycles of neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse free survival（RFS）	Means the time from the date of the curative surgery to the date of relapse or death.	3 years
AE	Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	Rate of residual tumor cells not detected by pathology in excised tissue samples.	Within one week after surgery
Major pathological response rate (MPR)	The percentage of active tumor cells in excised tissue samples is less than 10% of the rate.	Within one week after surgery
surgery rate	Proportion of patients with final surgical resection among enrolled surgically resectable patients.	Within one week after surgery
Radical (R0) resection rate	No residual cancer cells on the margins	Within one week after surgery
Objective response rate (ORR)	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR) or partial remission (PR) as rated according to RECIST 1.1 criteria. If efficacy of CR or PR is achieved, subjects must be confirmed not less than 4 weeks ± 7 days after the initial evaluation.	Within 2 weeks prior to surgery
Disease control rate (DCR)	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR), partial remission (PR), and stable disease (SD) as rated according to RECIST 1.1 criteria.	Within 2 weeks prior to surgery
Overall survival (OS)	Defined as the time between the date of first dose and the death of the subject due to all causes. Subjects who were alive at the last follow-up visit had OS counted as data censored at the time of the last follow-up visit. The OS of subjects who were lost to follow-up was counted as data censored at the time of last confirmed survival prior to the lost follow-up. OS for data censoring was defined as the time from first dose to censoring.	5 years

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University
• Investigators: Principal Investigator: Yufeng Chen, Zhangzhou Hospital of Fujian Medical University; Principal Investigator: Maolin Yan, Fujian Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2023
• Primary Completion (Estimated): February 23, 2029
• Study Completion (Estimated): February 23, 2029

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 27, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant treatment; apatinib; gemcitabine and cisplatin; adebrelimab; biliary tract malignancies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib; Gemcitabine
• Other Study ID Numbers: 23-OBU-FJ-BTC-II-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No