A Clinical Study of PD-L1 Antibody ZKAB001 Combined With Capecitabine in Resected Biliary Tract Cancer

NCT04608786 | Unknown Phase 1

• 1 other identifier: NTL-LEES-2019-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib, open-label,single-arm, clinical study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor ) combined with capecitabine as adjuvant chemotherapy for patients with biliary tract cancers after radical resection.After completing 8 courses of combined treatment ,ZKAB001 was continued to be administered separately once 3 weeks for a total of 16 cycles or 1 year.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  Adverse events of level 3 or above related to the study drug occurring within 21 days after the first dose as assessed by CTCAE v5.0.

  21 days after first dose

• Recommended phase II dose (RP2D)

  DLT occurs in no more than 1/6 subjects, this dose is defined as RP2D.

  21 days after first dose

Secondary Outcomes (6)

• AUC(0-t)

  16 periods or 1 year

• Cmax

  16 periods or 1 year

• Tmax

  16 periods or 1 year

• Disease-free Survival

  up to 24 months

• Overall survival (OS)

  up to 24 months

Study Arms (1)

Combined the therapy using Capecitabine and PD-L1

EXPERIMENTAL

PD-L1 antibody ZKAB001 D1 5mg/kg every three weeks,up to 16 cycles or 1 year of treatment or the patient has tumor recurrence or metastasis Capecitabine 1000mg / m2/time, 2 times/d for 2 weeks, followed by 1 week of stopping ,three weeks is a course of treatment with a total of 8 courses, or the patient has tumor recurrence or metastasis

Drug: ZKAB001 5mg/kg; Drug: Capecitabine

Interventions

ZKAB001 5mg/kg DRUG

ZKAB001 D1 IV 5mg/kg every three weeks,up to 16 cycles or 1 year

Also known as: PD-L1 monoclonal antibody

Combined the therapy using Capecitabine and PD-L1

Capecitabine DRUG

Capecitabine po 1000mg / m2/time, 2 times/d for 2 weeks, followed by 1 week of stopping ,three weeks is a course of treatment with a total of 8 courses

Combined the therapy using Capecitabine and PD-L1

Eligibility Criteria

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

You may qualify if:

• both men and women, age ≥ 18 years old；
• A histopathological or cytological diagnosis of gallbladder cancer and extrahepatic cholangiocarcinoma after radical resection
• Postoperative pathological stage is T2-4 or N1 R0/R1 resection；
• No more than 12 weeks from radical resection；
• Eastern Cooperative Oncology Group(ECOG) performance status score 0-1;
• Estimated life expectancy \>6 months;
• Biliary drainage is in good condition, no current infection ;
• Have not received radiotherapy, chemotherapy, or immunotherapy for the primary tumor;
• The function of important organs meets the following requirements:
• (1) Blood routine test: absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥100g/L; (2) Biochemical tests : ALT, AST ≤ 2.5×ULN; ALB≥ 35g/L;total bilirubin ≤3×ULN; serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥50 mL/min(Crockcroft-Gault formula); 10.Subjects voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with the follow-up.

You may not qualify if:

• Local recurrence or distant metastasis (including ascites or malignant pleural effusion);
• Severe cardiovascular disease, such as New York Heart Association (New York Heart Association, NYHA standard) heart failure above grade 2, unstable angina, unstable arrhythmia, or color photos of the heart suggest LVEF (left ventricular ejection fraction) )\<50%;
• Known allergy or hypersensitivity to monoclonal antibodies or fluorouracil drugs or their analogues;
• Subjects with known, active or suspicious autoimmune diseases, who are in a stable state and do not require systemic immunosuppressive therapy can be included in the group;
• Subjects were treated with immunosuppressants or systemic or absorbable topical corticosteroids within 2 weeks before the first study to achieve immunosuppressive purposes (\>10mg/day prednisone or equivalent dose) ;
• Suffered from other active malignancies within 5 years before the first administration of the study drug. Cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc. can be included in the group;
• Any active infection that requires systemic anti-infective treatment occurs within 14 days before the first medication;
• Have active tuberculosis in the past 1 year, regardless of treatment;
• Live attenuated vaccines have been used within 28 days before screening;
• Subjects who have previously received allogeneic bone marrow transplantation or solid organ transplantation;
• Have received any other experimental drug treatment within 28 days before signing the ICF;
• People who have difficulty swallowing or have known drug absorption disorders;
• Women who are pregnant or breastfeeding;
• Subjects of childbearing age who refuse to use effective contraceptive measures;

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Renji Hospital Affiliated to School of Medicine, Shanghai Jiaotong University

Shanghai, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: October 29, 2020
• Study Start: February 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: January 11, 2022

Record last verified: 2022-01

Locations

CN (1)