Phase I Clinical Study of Safety，Tolerability， Pharmacokinetics and Pharmacodynamics of Recombinant Humanized Cytotoxic T Lymphocyte Antigen 4 Single Domain Antibody Fc Fusion Protein Injection in Subjects With Advanced Solid Tumors

Changchun Intellicrown Pharmaceutical Co. LTD1 site in 1 country39 target enrollmentJanuary 9, 2020

ConditionsAdvanced Solid Tumors

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Solid Tumors
Sponsor: Changchun Intellicrown Pharmaceutical Co. LTD
Enrollment: 39
Locations: 1
Primary Endpoint: KN044 of adverse event
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multicenter, dose-escalation phase I study to assess the safety, tolerability and preliminary efficacy of KN044 in participants with all advanced solid tumors who are not able to have current standard anti-tumor therapies. The purpose of this study is to determine the maximum tolerated dose (MTD) , to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN044 as a single agent in adult participants with advanced solid tumors.

Detailed Description

This study will involve patients and follow the standard "3 + 3"design. KN044 will be antimedical intravenously over 30 minutes with planned doses of 0.03, 0.1, 0.3, 1, 3, 6,10 mg/kg Once every 3 weeks for first 4 doses, then every 3, or 6, or 12 weeks for up to 1 year if no intolerable toxicities occur and per agreement with investigator antimedical monitor based on emerging data.

Registry

clinicaltrials.gov

Start Date

January 9, 2020

End Date

August 1, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Changchun Intellicrown Pharmaceutical Co. LTD

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects can understand informed consent, voluntarily participate and sign informed consent.
•Tumor subject type Clinical diagnosis of advanced malignant tumors. Patients diagnosed by pathology and/or cytology; malignant melanoma, patients with advanced renal cell carcinoma, colorectal cancer, lung cancer, breast cancer, prostate cancer, etc. are preferred; the inclusion of melanoma is pathological and / or cytologically undiagnosed unresectable patients with stage 3b/3c or stage 4 (M1a / M1b) melanoma, in which patients with stage IV M1b have to meet the following requirements: no more than 5; the longest path of a single lesion must not exceed 20 mm; the sum of the longest diameters of the cumulative lesions must not exceed 50 mm.
•Subjects with locally advanced (non-resectable) and / or metastatic solid tumor that has progressed after standard therapies or no standard therapy exists.
•Previous anti-tumor therapy (including endocrine chemoradiotherapy/radiotherapy, targeted therapy) ended more than 4 weeks and has been restored to baseline or ≤ grade 1 from previous adverse events following \[Common Criteria for Assessment of Adverse Events (CTCAE) version 5.0\] (except for patients with hair loss).
•18-75 years of age, male or female; 10)Eastern Cooperative Oncology Group score 0 or 2; Life expectancy ≥ 3 months.
•Previous major surgery ≥1 month ago.
•Must have adequate organ function, prior to start of KN044, including the following:
•white blood cell count ≥ 3.0 × 109 / L;
•absolute neutrophil count (ANC) ≥ 1.5 ×109/L;
•platelet count ≥ 100 × 109/L;

Exclusion Criteria

•At the discretion of the investigator, there are both serious medical conditions that may harm the safety of the subject or affect the subject's completion of the study, including but not limited to: severe heart disease, cerebrovascular disease, uncontrolled diabetes, Insulin dependent diabetes, serious infection;Thyroid disease
•Accepted any other anti-tumor drug therapies, or other immunological anti-tumor treatments, including but not limited to PD-1/L1 inhibitors before the first KN044 dosing.
•Pregnant or nursing females
•Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure New York Heart Association III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, ECG QT interval（fridericia)\> 450msec, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)；Hypertension (defined as sustained systolic blood pressure\> 150 mm Hg and / or post-diastolic blood pressure with antihypertensive drugs\> 100 mm Hg;
•suffering from mental disorders, infectious diseases, and skin diseases that are difficult to control;
•Known active hepatitis B or C or known infection with HIV .
•History of life-threatening hypersensitivity, or known to be allergic to protein drugs or recombinant proteins or any ingredients in KN044 drug formulation
•Known severe bleeding factors that can affect venous blood sampling;
•Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (per investigator assessment).
•Subjects with active autoimmune disease or a documented medical history of autoimmune disease or symptoms that require systemic use of steroid and/or immunosuppressant. Exceptions are subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy.

Outcomes

Primary Outcomes

KN044 of adverse event

Time Frame: through study completion, an average of 210 days

the adverse events are recorded according to the actual occurrence

Dose-limiting toxicity for The maximum tolerated dose

Time Frame: up to 6 weeks

Dose-limiting toxicity observation period 6 weeks after the first dose

KN044 of abnormalities of physical findings and laboratory tests,

Time Frame: through study completion, an average of 210 days

The data of the clinical research center is collected and analyzed according to the time point of the test flow chart

Secondary Outcomes

PK parameters: Cmax(an average of 126 days)
PK parameters: Area under curve (AUC)(an average of 126 days)
PK parameters: t1/2(an average of 126 days)
PK parameters: Clearance rate (CL)(an average of 126 days)
PK parameters: dose proportionality(an average of 126 days)
Anti-tumor activity as measured by ResponseEvaluationCriteriainSolidTumors Version1.1(RESISTv1.1)(During the treatment period , the tumor was evaluated every 6 weeks, then every 9 weeks.)
PK parameters: Vss(an average of 126 days)
Incidence of the positive anti-drug antibodies and titers of anti-drug antibodies(an average of 147 days)