A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Locally Advanced and Metastatic Urothelial Carcinoma

NCT03676946 | Unknown Phase 1

• 1 other identifier: NTL-LEES-2017-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1+2, open-label, dose-escalation, and multidose 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 on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with locally advanced and metastatic urothelial carcinoma.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.

  28 days after first dose

Secondary Outcomes (12)

• Maximal tolerable dose(MTD)

  28 days after first dose

• The overall response rate(ORR)

  through study completion, an average of 2 year

• AUC(0-t)

  24 periods or 1 year

• AUC(INF)

  24 periods or 1 year

• Cmax

  24 periods or 1 year

Study Arms (3)

ZKAB001 5mg/kg

EXPERIMENTAL

Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.

Drug: ZKAB001 5mg/kg

ZKAB001 10mg/kg

EXPERIMENTAL

Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.

Drug: ZKAB001 10mg/kg

ZKAB001 15mg/kg

EXPERIMENTAL

Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.

Drug: ZKAB001 15mg/kg

Interventions

ZKAB001 5mg/kg DRUG

5mg/kg/times bi-week IV administration of ZKAB001

Also known as: PD-L1 monoclonal antibody

ZKAB001 5mg/kg

ZKAB001 10mg/kg DRUG

10mg/kg/times bi-week IV administration of ZKAB001

Also known as: PD-L1 monoclonal antibody

ZKAB001 10mg/kg

ZKAB001 15mg/kg DRUG

15mg/kg/times bi-week IV administration of ZKAB001

Also known as: PD-L1 monoclonal antibody

ZKAB001 15mg/kg

Eligibility Criteria

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

You may qualify if:

• The subject voluntarily gives written informed consent to participate in the study.
• Female and male patients aged between 18 and 75 (inclusive).
• Subjects must have a histologically and/or cytologically confirmed diagnosis of urothelial carcinoma and the recurrence or metastasis is confirmed again after recurrence, and must have failed or are intolerable to standard therapies or for whom no standard therapies exist.
• Must have measurable disease with at least 1 unidimensional measurable lesion (recorded as the maximum diameter) based on RECIST 1.1.
• Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, with estimated life expectancy of at least 3 months.
• Adequate blood routine, hepatic and renal function:
• )neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L ; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN (upper limit of normal ); 6)ALT and AST≤1.5 x ULN, such as liver metastasis, ALT (alanine transaminase) and AST≤5 x ULN; 7)serum Cr≤1.25 x ULN or endogenous creatinine clearance≥50 ml/min (according Cockcroft Gault formula).
• Female patients of reproductive age should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin (HCG) examination must be negative within 7 days before the study was enrolled.

You may not qualify if:

• Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, and still need medical intervention in adult; Patients need bronchodilators for medical intervention of asthma.
• Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses \>10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
• Have received any form of organ transplantation, including allogeneic stem cell transplantation.
• Known allergy to macromolecular protein inhibitors or any of the components of ZKAB001.
• Suffering from other malignant tumors other than this diseases in 5 years except skin basal cell and squamous cell carcinoma or cervical carcinoma in situ.
• Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose \>10mg/day prednisone or equivalent) less than 2 weeks.
• Patients with clinical symptoms or heart diseases that cannot be well controlled, such as heart failure above New York Heart Association (NYHA) 2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, left ventricular ejection fraction \< 50% at rest as shown in the ultrasound cardiogram.
• Active infection, or unexplained fever\> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
• Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
• The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
• Patients may need to receive other systemic cancer treatment during study period.
• Prior therapy with an anti-PD 1, anti-PD L1, or anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) antibody (or any other agents that target immunoregulatory receptor).
• Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus (HPV) vaccine) within 28 days before screening.
• History of mental drug abuse, alcohol abuse or drug abuse.
• Pregnant or lactating women.

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Beijing Tumor Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Jun Guo, MD

  Beijing Tumor Hospital

  STUDY DIRECTOR

Central Study Contacts

Jun Guo, MD

CONTACT

010-88121122; guoj307@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 19, 2018
• Study Start: October 10, 2018
• Primary Completion: February 14, 2020
• Study Completion: June 23, 2023
• Last Updated: September 26, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)