A Clinical Study of PD-L1 Antibody ZKAB001（Drug Code） in Recurrent or Metastatic Cervical Cancer

NCT03676959 | Unknown Phase 1

• 1 other identifier: NTL-LEES-2017-02
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics(PK) 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 recurrent or metastatic cervical cancer.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (3)

• RP2D

  Recommended phase II dose.

  28 days after first dose

• Objective response rate

  The proportion of subjects who achieved the best objective response rate (PR or CR).

  2 years

• Tolerance

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

Secondary Outcomes (8)

• Effect of ZKAB001 on T cell function and cytokine expression

  through study completion, an average of 2 years

• The number of subjects presenting detectable anti drug antibodies (ADAs)

  through study completion, an average of 2 years

• Receptor occupancy

  through study completion, an average of 2 years

• PD-L1 expression

  through study completion, an average of 2 years

• progression free survival（PFS）

  through study completion, an average of 2 years

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 10 mg/kg

EXPERIMENTAL

Three or six patients will be treated with the dose of 10 mg/kg/time of ZKAB001 IV bi-weekly. DLT will be observed within 28 days after administration.

Drug: ZKAB001 10mg/kg

ZKAB001 15 mg/kg

EXPERIMENTAL

Three or six patients will be treated with the dose of 15 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 10 mg/kg

ZKAB001 15mg/kg DRUG

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

Also known as: PD-L1 monoclonal antibody

ZKAB001 15 mg/kg

Eligibility Criteria

• Age: 18 Years+
• 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 subjects aged≥18 years.
• Recurrent or metastatic cervical cancer was diagnosed by histopathology or cytology and received first-line platinum-containing regimens that failed or could not be tolerated. The definition of first-line failure: progress during adjuvant therapy or within 6 months after the end of treatment, and the first progress after palliative treatment.
• Based on RECIST1.1, imaging evaluation confirmed that there was at least one measurable disease.
• 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:
• \) Absolute neutrophil count（ANC）≥109/L 2) Platelets ≥100x109/L 3) Hemoglobin ≥9g/dL 4) Serum albumin ≥2.8g/dL 5) Bilirubin ≤1.5x Upper limit of normal（ULN） 6) ALT and AST ≤1.5xULN, if If liver metastases are present, alanine transaminase（ALT） and aspartate transaminase（AST） should be ≤5xULN 7) Creatinine clearance rate ≥50ml/min (Cockcroft-Gault equation) 7.Female reproductive subjects 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 subject is enrolled.

You may not qualify if:

• There are known active or suspected autoimmune diseases. Those who are in a stable state and do not need systemic immunosuppressive therapy can be included.
• 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 for skin basal cell and squamous cell carcinoma.
• 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 diseases of the heart 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, have left ventricular ejection fraction \< 50% at rest in the ultrasound cardiogram.
• Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks.
• Within 14 days before the first use of the drug, any active infection requiring systematic anti-infective treatment.
• Human immunodeficiency virus (HIV) positive, untreated active hepatitis (hepatitis B surface antigen positive and peripheral blood HBV-DNA titer ≥ 500IU/ml or positive copy number detected by the research center; hepatitis C virus antibody positive)
• There is a history of active pulmonary tuberculosis within 1 year before entering the group.
• 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.
• Received blood transfusion and hematopoietic stimulating factors, such as colony stimulating factor, erythropoietin, thrombopoietin, etc., within 14 days before screening.
• 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).

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100000, China

RECRUITING

Related Publications (1)

• An J, Tang J, Li BX, Xiong H, Qiu H, Luo L, Wang L, Wang D, Zhou Q, Xu Q, Song H, Zhang Y, Zhang H, Li Y, Yu X, Zhang J, Ng R, Zhao W, Wong M, Dai X, Li G, Wu L. Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study. Clin Cancer Res. 2022 Dec 1;28(23):5098-5106. doi: 10.1158/1078-0432.CCR-22-1280.

  PMID: 36136294 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• lingying Wu, M.D

  Tumor Hospital of the Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

lingying Wu, M.D

CONTACT

13910865483; wulingying@csco.org.cn

hong Fang, master

CONTACT

010-87788714

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 12, 2018
• First Posted: September 19, 2018
• Study Start: August 16, 2018
• Primary Completion: May 15, 2022
• Study Completion: October 15, 2022
• Last Updated: May 13, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)