Safety and Efficacy of the Fully Humanized Anti - VEGF Monoclonal Antibody LYN00101

March 10, 2020 updated by: Lynkcell Inc.

Phase I Study of the Safety, Tolerability,Pharmacokinetics and Pharmacodynamics of the Fully Humanized Anti - VEGF Monoclonal Antibody LYN00101 With Blocking of Autocrine Loops VEGFR1/2/3

The purpose of this study is evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of of fully human anti - VEGF monoclonal antibody LY00101 and explore the potential prognostic and predictive biomarkers.

This study will not take into account the results of molecular-genetic tests of patients enrolled in the study

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Tumors can be inactive for years, until transformation of cells into an angiogenic phenotype occurs. This phenomenon is known as angiogenic switch. It is based on balance between inhibitors and activators of angiogenesis.

Multiple genetic changes and processes leading to malignancies, such as activation of oncogenes, can trigger angiogenic switch.

Simple diffusion of nutrients and oxygen normally occurs within not more than 1-2 mm of tumor tissue. For further growth, blood supply and development of the vasculature are necessary.

Angiogenesis level in a tumor and it's metastasis activity has correlation with density of microvessels in a primary tumor and significantly affects disease prognosis.

Angiogenesis in a body is regulated through Vascular endothelial growth factor (VEGF) and its receptors.

There is a unique binding pattern of corresponding receptors typical for all members of the VEGF family:

  • VEGF-A binds with VEGFR1 and VEGFR2
  • VEGF-B and PlGF bind and activate receptor VEGFR1 only
  • VEGF-C and VEGF-D communicate with receptor VEGFR3 (Flt4), triggering lymphangiogenesis, and demonstrate activity correlated with VEGFR2.

According to studies, VEGFR1 binds to the ligand with the highest affinity, binding VEGF and inhibiting VEGF-mediated signaling.

The VEGF-VEGFR2 binder induces autophosphorylation (and partial dimerization) of the catalytic domain of the PI3K / v-akt signaling pathway receptor (Phosphoinositide 3-kinase / murine thymoma viral oncogene homolog - Akt or serine / threonine protein kinase B, PKB), as well as Raf and MAP2K, which further phosphorylate MAPK (Erk).

Monoclonal antibody LYN00101 is not only a potent inhibitor of VEGF, also blocks autocrine growth factor loops by inhibiting VEGF and VEGFR 1/2/3 receptors and effectively blocking neoangiogenesis.

The purpose of this study is evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of of fully human anti - VEGF monoclonal antibody LY00101 and explore the potential prognostic and predictive biomarkers.

This study will not take into account the results of molecular-genetic tests of patients enrolled in the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients with histopathologically-documented, measurable or non measurable {evaluable}, advanced solid tumors refractory
  • a life expectancy of >3 months
  • ECOG performance status score of ≤ 2 at study entry
  • able to provide written informed consent.
  • use of effective contraceptive measures if procreative potential exists.
  • an absolute neutrophil count ≥1500/mm3
  • a hemoglobin level ≥ 9gm/dL
  • a platelet count ≥100,000/mm3
  • a total bilirubin level ≤1.5 x the ULN
  • aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤2.5 x the ULN or ≤5 x the ULN if known liver metastases
  • adequate renal function, as defined by a serum creatinine level ≤1.5 x the ULN.

Exclusion Criteria:

  • patients with any active infection (nail bed induced fungal infections were excluded), chronic infections, and tuberculosis history.
  • the females were pregnant, or lactating or showed positive urine pregnancy reaction during screening.
  • patients with severe heart disease, heart failure, asthma, chronic obstructive pulmonary disease or neuropsychiatric diseases.
  • uncontrolled diabetes or poor compliance with hypoglycemics;
  • the presence of chronically unhealed wound or ulcers
  • other chronic diseases, which, in the opinion of the investigator, could compromise safety of the patient or the integrity of study.
  • newly-diagnosed or symptomatic brain metastases (patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids for brain edema). Anticonvulsants are allowed.
  • peritoneal carcinomatosis
  • pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast-feeding (for female patients only).
  • a known history or clinical evidence of a deep vein or arterial thrombosis, or pulmonary embolism
  • less than six weeks from last infusion of any anti-VEGF monoclonal antibody therapy
  • known history of human immunodeficiency virus infection (HIV).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LYN00101
Intravenous Infusion at the rate of 8 mg/kg of the patient's weight every 14 days.
Biological: LYN00101

Concentrate for intravenous infusions (10 mg / ml) with Molecular Weight 150 - 151 kDa.

Each cycle of treatment consists of 24 weeks. Patients who enroll into this study will receive an infusion of assigned dose of LYN00101 biweekly. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 10mg/kg, starting from 8 mg/kg.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve after single dose use
Time Frame: up to 14 days
Area under the concentration-time curve from 0 to ∞ with extrapolation of the final phase of the drug distribution
up to 14 days
Peak plasma concentration after single dose use
Time Frame: up to 14 days
Peak plasma concentration (Cmax) of T1h
up to 14 days
Area under the plasma concentration after single - dose use
Time Frame: up to 14 days
Area under the plasma concentration versus time curve( AUC(0-t)) of T1Hh
up to 14 days
Elimination rate constant after single - dose use
Time Frame: up to 14 days
Elimination rate constant of T1h
up to 14 days
Time to peak after single dose use
Time Frame: up to 14 days
Time to peak(Tmax) of T1h
up to 14 days
Half time after single dose use
Time Frame: up to 14 days
Half time (t1/2) of T1h
up to 14 days
volume of distribution after single - dose use
Time Frame: up to 14 days
Apparent VD - volume of distribution of T1h
up to 14 days
Total body clearance after single-dose use
Time Frame: up to 14 days
Total body clearance (CLs)of T1h
up to 14 days
Mean residence time after single-dose use
Time Frame: up to 14 days
MRT - Mean residence time of T1h
up to 14 days
Time to peak after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Time to peak(Tmax) of T1h
up to 24 weeks
Elimination rate constant after Each Subsequent Introductions (multiple dose)
Time Frame: up to 24 weeks
Elimination rate constant of T1h
up to 24 weeks
Area under the plasma concentration versus time curve after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Area under the plasma concentration versus time curve( AUC(0-t)) of T1Hh
up to 24 weeks
Cmax of T1h after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Peak plasma concentration (Cmax) of T1h
up to 24 weeks
AUC(0-∞) of T1h after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Area under the plasma concentration versus time curve(AUC(0-∞))of T1h
up to 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average plasma concentration after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Average plasma concentration in steady state/Css_avg/ of T1h
up to 24 weeks
Vss of T1h after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Apparent volume of distribution in steady state /Vss/ of T1h
up to 24 weeks
CT or MRI or PET/CT Control
Time Frame: after 8 weeks
Tumor Necrosis and Dynamic of the Treatment ( by CT or MRI or PET/CT)
after 8 weeks
Area under the plasma concentration after each subsequent introduction (multiple dose)
Time Frame: up to 24 weeks
Area under the plasma concentration versus time curve in steady state (AUCss) of T1h
up to 24 weeks
Blood C-reactive protein level after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
C-reactive protein/CARP/
up to 24 weeks
Blood Test / morphology after Each Subsequent Introduction (multiple dose)
Time Frame: every week (up to 24 weeks)
Blood Test / morphology
every week (up to 24 weeks)
TNF-α level after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Tumor Necrosis Factor -alpha (TNF-α)
up to 24 weeks
PGA after Each Subsequent Introduction (multiple dose)
Time Frame: every week up to 24 weeks
Physician's Global Assessment /PGA/
every week up to 24 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
CLs after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Total body clearance CLs (T1h)
up to 24 weeks
Apparent VD - volume of distribution of T1h after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Apparent VD - volume of distribution of T1h
up to 24 weeks
Half time (t1/2) of T1h after Each Subsequent Introduction (multiple dose)
Time Frame: up to 24 weeks
Half time (t1/2) of T1h
up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lynkcell Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 3, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 11, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LY233-234V

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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