Adebrelimab and a TKI in Combination With GEMOX in First-line Treatment of Advanced Biliary Tract Cancers (BTC)

NCT06320301 | Recruiting Phase 2

• 1 other identifier: SYSKY-2024-027-01
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with advanced biliary tract malignant tumors who had not received systematic treatment before and could not be cured were selected as the subjects of the study. The primary endpoint of the study was investigator-assessed 6-month progression-free survival (6-month PFS%) based on the RECIST v1.1 criteria, and 43 subjects were planned to be enrolled. Patients eligible for enrollment will receive Adebrelimab and a tyrosine kinase inhibitor (TKI) in combination with gemcitabine and oxaliplatin (GEMOX).

Conditions

Biliary Tract Cancer; Gemox Chemotherapy

Keywords

Biliary tract cancer; GEMOX; PD-L1; Adebrelimab; TKI

Outcome Measures

Primary Outcomes (1)

• the effectiveness of first-line treatment with Adebrelimab and a tyrosine kinase inhibitor (TKI) in combination with gemcitabine and oxaliplatin (GEMOX) in patients with advanced BTC

  To evaluate the effectiveness of first-line treatment with Adebrelimab and a tyrosine kinase inhibitor (TKI) in combination with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer by assessing 6-month progression-free survival (6-month PFS%)

  From enrollment to 6 months

Secondary Outcomes (6)

• To assess the progression-free survival (PFS)

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• To evaluate the time to progression (TTP)

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• To evaluate the disease control rate (DCR),

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• To evaluate the objective response rate (ORR)

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• To evaluate the duration of response (DoR)

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

Other Outcomes (6)

• To explore the correlation between biomarkers and the efficacy of the combination regimen.

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• The PFS based on an immunomodified RECIST (imRECIST）

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

• The TTP based on an immunomodified RECIST (imRECIST）

  From the date of enrollment until the date of the first documented progression or death from any cause, assessed up to 16 months after the enrollment of the last patient.

Study Arms (1)

Adebrelimab + GEMOX + TKI

EXPERIMENTAL

Adebrelimab, 20 mg/kg, 30-minute intravenous infusion, once every 3 weeks (Q3W) TKI: Lenvatinib: 12 mg (3 capsules 4 mg) or 8 mg (2 capsules 4 mg) QD Apatinib: 250 mg orally, QD, 5 days on 2 days off or QOD Sorafenib: 0.4g (2 × 0.2g) twice or once daily Anlotinib: 12 mg orally before breakfast, QD. The drug was taken continuously for 2 weeks and stopped for 1 week. GEMOX: Gemcitabine 800mg/m2 and oxaliplatin 85mg/m2, IV, D2, D15, D29, until 6 cycles of treatment

Drug: Adebrelimab + GEMOX + TKI

Interventions

Adebrelimab + GEMOX + TKI DRUG

Adebrelimab 20 mg/kg, once every 3 weeks (Q3W), maintained for 1 year. The interval between two doses should not be less than 12 days. Tyrosine kinase inhibitor (TKI) Lenvatinib: 12 mg (3 capsules 4 mg) or 8 mg (2 capsules 4 mg) once daily (QD) at fixed times daily, on an empty stomach or with food; Apatinib: 250mg orally, QD, 5 days of medication, 2 days off (5 on 2 off) or once every other day (QOD), half an hour after meals; Sorafenib: 0.4g (2 × 0.2g) twice or once daily on an empty stomach or with a low-fat or medium-fat diet Anlotinib: 12 mg orally before breakfast, QD. The drug was taken continuously for 2 weeks and stopped for 1 week. GEMOX: gemcitabine 800mg/m2 and oxaliplatin 85mg/m2, intravenous infusion, D2, D15, D29, until 6 cycles of treatment were completed, or the patients who did not reach 6 cycles had intolerable adverse reactions, then the combination chemotherapy was terminated.

Also known as: Adebrelimab+ tyrosine kinase inhibitor (TKI) + gemcitabine - oxaliplatin (GEMOX)

Adebrelimab + GEMOX + TKI

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \) The patient voluntarily participated in the study and signed the informed consent;
• \) ≥ 18 years old (calculated on the day of signing the informed consent), male or female;
• \) Patients with advanced biliary tract malignant tumors confirmed by histopathology or cytology;
• \) Subjects must be able to provide fresh or archived tumor tissue (formalin-fixed, paraffin-embedded \[FFPE\] blocks or at least 5 unstained FFPE slides) and their pathology reports. If less than 5 unstained slides are available from the subject or tumor tissue is not available (e.g., because of exhaustion of previous diagnostic tests), enrollment may be allowed on a case-by-case basis after discussion;
• \) The subject is not suitable for surgery, or has progressed after surgery and/or local treatment;
• \) Patients with progression after local therapy, where local therapy (including but not limited to surgery, radiotherapy, arterial embolization, arterial infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) has been completed at least 4 weeks prior to the baseline imaging scan, Toxicity (except alopecia) caused by topical treatment must be restored to the National Cancer Institute-Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) rating ≤ 1;
• \) No previous systemic therapy for BTC
• \) At least one measurable lesion (according to the requirements of RECIST v1.1, the long diameter of the measurable lesion on spiral CT scan is ≥ 10 mm or the short diameter of the enlarged lymph node is ≥ 15 mm; the lesion that has received local treatment in the past can be used as the target lesion after the progress is confirmed according to the criteria of RECIST v1.1)
• \) The physical condition score of the Eastern Cooperative Oncology Group (ECOG) was 0 \~ 2 (see Attachment 1 for the ECOG score standard);
• \) Expected survival ≥ 12 weeks;
• \) The functions of main organs are basically normal, and there are serious abnormalities of blood, heart, lung, liver, kidney, bone marrow and other functions and immunodeficiency diseases, which meet the requirements of the protocol: A) Blood routine examination: (except for hemoglobin, no blood transfusion within 14 days before screening, no use of granulocyte colony-stimulating factor \[G-CSF\], and no use of corrective therapy within 7 days) I. Hemoglobin ≥ 90 G/L; II. Neutrophil count ≥ 1.5 × 109/L; III. Platelet count ≥ 50 × 109/L; B) Biochemical examination: (no albumin transfusion within 14 days) I. Serum albumin ≥ 29 G/L; II. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN); III. Total bilirubin (TBIL) ≤ 1.5 times ULN;
• IV. Creatinine Cr ≤ 1.5 X ULN or Cr clearance \> 50 mL/min (Cockcroft-Gault formula below):
• Male: Cr clearance = ( (140-age) × body weight)/ (72 × blood Cr) Female: Cr clearance = ( (140-age) × body weight)/ (72 × blood Cr) × 0.85 Weight unit: kg; Blood Cr unit: mg/mL; V. Urine protein \< 2 + (if urine protein ≥ 2 +, 24-hour (H) urine protein can be quantified, and 24-hour urine protein \< 1.0 G can be included in the group); C) Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (can be screened for the use of stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin and INR is within the expected therapeutic range of anticoagulant); D) Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be examined, and if T3 and T4 levels are normal, they can be included; Color Doppler echocardiography: left ventricular ejection fraction (LVEF) was greater than or equal to 60%.
• \) Fertile women: must agree to abstain from sex (abstain from heterosexual intercourse) or use a reliable, effective method of contraception for at least 120 days from the signing of the informed consent until the final administration of the study drug. Serum HCG test must be negative within 7 days before the start of study treatment; And must be non-lactating. A woman is considered fertile if she has menstruated, has not yet reached postmenopausal status (no continuous periods for ≥12 months, no cause other than menopause is found), and has not undergone sterilization (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
• \) For male patients whose partner is a woman of reproductive age, they must agree to abstain from sex for at least 120 days from the signing of the informed consent until the final administration of the study drug, or to use a reliable and effective method of contraception. Male subjects also had to agree not to donate sperm during the same time period. Male subjects with a pregnant partner are required to use condoms and do not need to use other methods of contraception.

You may not qualify if:

• \) Active malignancies other than BTC within 5 years or at the same time. Cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc., could be included in the group.
• \) Patients who are preparing for or have previously received organ or allogeneic bone marrow transplantation;
• \) Other investigational drug treatment received within 28 days prior to the start of study treatment;
• \) Moderate and severe ascites with clinical symptoms, i.e. requiring therapeutic puncture, drainage or Child-Pugh score \> 2 (except for those with only a small amount of ascites on imaging but without clinical symptoms); uncontrolled or moderate or more pleural effusion and pericardial effusion;
• \) If there is a history of gastrointestinal bleeding or a definite tendency of gastrointestinal bleeding within 6 months before the start of study treatment, such as bleeding risk or severe esophageal and gastric varices, local active gastrointestinal ulcer lesions, and persistent positive fecal occult blood, they should not be included in the group (if the fecal occult blood is positive at baseline, it can be reexamined, and if it is still positive after reexamination, Gastroduodenal endoscopy (EGD) is required, and esophagogastric varices with EGD suggesting a risk of bleeding are not eligible);
• \) Abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6 months prior to the start of study treatment;
• \) Known presence of inherited or acquired bleeding (e.g., coagulopathy) or thrombophilia, e.g., in patients with hemophilia; current or recent (within 10 days prior to the start of study treatment) use of full-dose oral or injectable anticoagulants or thrombolytics for therapeutic purposes (low-dose aspirin, low-molecular-weight heparin, prophylactic use permitted);
• \) current or recent use (within 10 days prior to study treatment) of aspirin (\> 325 mg/day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilostazol;
• \) Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the start of study treatment;
• \) Clinical symptoms or diseases of the heart that are not well controlled, such as:
• LVEF (left ventricular ejection fraction) \< 50% according to New York Heart Association (NYHA) standard II or above cardiac dysfunction or cardiac color Doppler ultrasound examination;
• unstable angina pectoris;
• Myocardial infarction within 1 year prior to the start of study treatment;
• Supraventricular or ventricular arrhythmias of clinical significance require treatment or intervention;
• QTc \> 450ms (male); QTc \> 470ms (female) (QTc interval is calculated by Fridericia formula; if QTc is abnormal, it can be detected three times at an interval of 2 minutes, and the average value is taken);

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Suzhou Suncadia Biopharmaceuticals Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guanzhou, Guangdong, 512000, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

gemcitabine-oxaliplatin regimen

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Central Study Contacts

Wenbin Li, archiater

CONTACT

86-13602773101; gzsurgeon@163.com

Junkai Ren

CONTACT

86-18664506517; rjk119234@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: March 20, 2024
• Study Start: April 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)