Phase I Study of KN044 in Locally Advanced/Metastatic Solid Tumors

NCT04126590 | Unknown Phase 1 FDA Drug

• 1 other identifier: KN0440101a
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Keywords

Adverse Event; Anti-Drug Antibodies; Complete Response

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity for The maximum tolerated dose

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

  up to 6 weeks

• KN044 of adverse event

  the adverse events are recorded according to the actual occurrence

  through study completion, an average of 210 days

• KN044 of abnormalities of physical findings and laboratory tests,

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

  through study completion, an average of 210 days

Secondary Outcomes (8)

• PK parameters: Area under curve (AUC)

  an average of 126 days

• PK parameters: Cmax

  an average of 126 days

• PK parameters: Clearance rate (CL)

  an average of 126 days

• PK parameters: t1/2

  an average of 126 days

• PK parameters: Vss

  an average of 126 days

Study Arms (7)

KN044 0.03 mg/kg dose group

EXPERIMENTAL

KN044 0.03 mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 0.1 mg/kg dose group

EXPERIMENTAL

KN044 0.1 mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 0.3mg/kg dose group

EXPERIMENTAL

KN044 0.3mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 1 mg/kg dose group

EXPERIMENTAL

KN044 1 mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 3 mg/kg dose group

EXPERIMENTAL

KN044 3 mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 6mg/kg dose group

EXPERIMENTAL

KN044 6mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

KN044 10mg/kg dose group

EXPERIMENTAL

KN044 10mg/kg dose group,once every 3 weeks，a total of four cycles

Biological: KN044

Interventions

KN044 BIOLOGICAL

The modified phase I "3 + 3" study design was used in dose escalation from low dose to high dose to determine the MTD.Sequential assignment of Patient cohorts to one of five dose levels of KN044: 0.03mg/kg,0.3 mg/kg,1 mg/kg,3 mg/kg,6 mg/kg,10 mg/kg.

KN044 0.03 mg/kg dose group; KN044 0.1 mg/kg dose group; KN044 0.3mg/kg dose group; KN044 1 mg/kg dose group; KN044 10mg/kg dose group; KN044 3 mg/kg dose group; KN044 6mg/kg dose group

Eligibility Criteria

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

You may qualify if:

• Subjects can understand informed consent, voluntarily participate and sign informed consent.
• 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).
• 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;
• hemoglobin ≥ 9 g/dL
• serum albumin ≥ 2.5 g / dL;
• Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5× ULN (≤5 × ULN if with liver involvement)
• Renal: Serum creatinine ≤ 1.5×ULN or 24-hour Estimated clearance≥50 mL / min (Cockcroft and Gault formula);
• Coagulation tests International standardization ratio (INR) ≤ 1.5, prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
• Normal left ventricular ejection fraction (LVEF) ≥50% measured by multigated radionuclide angiography or Echocardiography.

You may not qualify if:

• 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.
• Use of more than 15 mg of prednisone or equivalent dose of steroids per day within 3 months of administration.
• Electrocardiogram QT interval (fridericia) \> 450 msec and severe arrhythmia requiring medication (except for atrial fibrillation or paroxysmal supraventricular tachycardia);
• Uncontrolled primary central nervous system tumors or central nervous system metastasis; based on screening brain magnetic resonance imaging (MRI), patients who have one of the following may not be excluded:
• No evidence of brain metastases or has to be clinically stable for at least 4 weeks
• Untreated brain metastases not needing immediate local therapy

Sponsors & Collaborators

• Changchun Intellicrown Pharmaceutical Co. LTD: lead

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100000, China

RECRUITING

MeSH Terms

Conditions

Pathologic Complete Response

Condition Hierarchy (Ancestors)

Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• chunmei Bai

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Rui Chen

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shiqi Bai

CONTACT

18943642700; baishiqi@intelli-crown.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: October 10, 2019
• First Posted: October 15, 2019
• Study Start: January 9, 2020
• Primary Completion: June 1, 2024
• Study Completion: August 1, 2024
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)