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

  • STATUS
    Recruiting
  • End date
    Jun 23, 2023
  • participants needed
    15
  • sponsor
    Lee's Pharmaceutical Limited
Updated on 14 February 2022
platelet count
renal function
monoclonal antibodies
doxorubicin
kidney function tests
neutrophil count
cancer chemotherapy
immunomodulators

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.

Description

The study will consist of 4 periods: Screening (up to 28 days), Lead-in period (Day -28), Treatment (up to 24 cycles or 1 year, whichever occurs first), and Follow-up (up to 2 years). There will be a lead-in period on Day -28 for each dose escalation cohort in which the single-dose pharmacokinetics(PK) of ZKAB001 will be characterized prior to initiation of continuous dosing in the first cycle of treatment. The lead-in period duration, PK time-points, doses and/or regimens used in subsequent cohorts may be modified based on the exposure (AUC) observed during the lead-in period (although the number of PK samples will not be increased). Treatment of continuous dosing is up to 24 cycles or 1 year, until as per investigator's opinion, subjects experience disease progression (evaluated by RECIST 1.1), no clinical benefit, or intolerable toxicity. If investigators suspect subjects experience pseudoprogression or has evidence to prove "mixed response", subjects can continue to accept treatment as investigator decided.

Details
Condition Osteosarcoma
Treatment ZKAB001 5mg/kg, ZKAB001 10mg/kg, ZKAB001 15mg/kg
Clinical Study IdentifierNCT03676985
SponsorLee's Pharmaceutical Limited
Last Modified on14 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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 GroupECOGperformance 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 acuity1.5 x 109 / L; 2)platelet count80 x
L; 3)hemoglobin90 g/L; 4)serum albumin28 g/L; 5)bilirubin1.5 x ULNupper
limit of normal; 6)Alanine transaminase ALTand AST1.5 x ULN, serum Cr1.25 x
ULN; 7) endogenous creatinine clearance50 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 gonadotropinHCG examination must be negative within 7
days before the subject is enrolled

Exclusion Criteria

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 AssociationNYHA 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-4Cytotoxic T Lymphocyte Antigen-4antibodies, or other drugs for immunomodulatory receptor preparations previously
Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirusHPVvaccine) within 28 days before screening
History of mental drug abuse, alcohol abuse or drug abuse
Pregnant or lactating women
Any mental condition that prevents the understanding or provision of the informed consent
It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the patients , family or social factors that may affect the study data and sample collection
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