A Clinical Study of PD-L1 Antibody ZKAB001(Drug Code) in Limited Stage of High-grade Osteosarcoma

NCT03676985 | Unknown Phase 1

• 1 other identifier: NTL-LEES-2017-03
• 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 limited stage of high-grade osteosarcoma of maintenance therapy after adjuvant chemotherapy.

Conditions

Osteosarcoma

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

• EFS(event-free survival)

  through study completion, an average of 3 years

• 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 5 mg/kg/time

EXPERIMENTAL

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

Drug: ZKAB001 5mg/kg

ZKAB001 10 mg/kg/time

EXPERIMENTAL

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

Drug: ZKAB001 10mg/kg

ZKAB001 15 mg/kg/time

EXPERIMENTAL

Three or six patients will treated with the dose of 15 mg/kg/time of ZKAB001 IV bi-weekly. DLT was 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 5 mg/kg/time

ZKAB001 10mg/kg DRUG

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

Also known as: PD-L1 monoclonal antibody

ZKAB001 10 mg/kg/time

ZKAB001 15mg/kg DRUG

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

Also known as: PD-L1 monoclonal antibody

ZKAB001 15 mg/kg/time

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The patient voluntarily gives written informed consent to participate in the study.
• Patients aged between 18 and 55 (inclusive).
• To diagnosed with limited stage of high-grade osteosarcoma (AJCC stage I-III) by histologically, the patients must have received neoadjuvant chemotherapy and adjuvant chemotherapy and primary tumor radical surgery (R0). The end of adjuvant chemotherapy should less than 12 weeks. Chemotherapy regimens must contain doxorubicin (ADM)/epirubicin (EPI)/pirarubicin (THP)/doxorubicin liposome (PLD) and cisplatin (DDP), the minimum cumulative doses are ADM 360 mg/m2, EPI 450mg/m2, THP 300mg/m2, PLD 240 mg/m2 and DDP 480 mg/m2.
• 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)Alanine transaminase （ALT）and AST≤1.5 x ULN, serum Cr≤1.25 x ULN; 7) endogenous creatinine clearance≥50 ml/min (according Gault Cockcroft formula).
• 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:

• Local recurrence or metastasis.
• 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, adult still need medical intervention; 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 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.
• Previous radiotherapy, chemotherapy, surgery or molecular targeted therapy, less than 3 weeks after treatment and before study drug; Patients whose adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
• 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.
• To receive other anti-tumor treatment during the study.
• To treated with other PD-1 and/or PD-1, or CTLA-4（Cytotoxic T Lymphocyte Antigen-4）antibodies, or other drugs for immunomodulatory receptor preparations previously.
• Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus（HPV）vaccine) within 28 days before screening.

Sponsors & Collaborators

• Lee's Pharmaceutical Limited: lead

Study Sites (1)

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, 200233, China

RECRUITING

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Osteosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• yang Yao, master

  600 yishan road, Shanghai

  STUDY DIRECTOR

Central Study Contacts

yang Yao, master

CONTACT

18930177737; yangyao_6@hotmail.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

Locations

CN (1)