Ovarian CancerPhase 1NCT03644459
Safety and Efficacy of the Fully Humanized Anti - VEGF Monoclonal Antibody LYN00101
A Phase 1 study testing LYN00101 in people with Ovarian Cancer and Cervical Cancer, run by Lynkcell Inc..
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ovarian Cancer, Cervical Cancer, Colorectal Cancer
- What is being tested?
- LYN00101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 3 Apr 2019to Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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).
About this study
Official title: 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
Read the 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.
- Conditions
- Ovarian Cancer, Cervical Cancer, Colorectal Cancer, Stomach Cancer
- Being tested
- LYN00101
- Keywords
- Tolerability, Safety, Humanized Anti-VEGF Monoclonal Antibody, autocrine loops, LYN00101
- Medical subject headings
- Ovarian Neoplasms, Uterine Cervical Neoplasms, Colorectal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LYN00101Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| LYN00101 | Experimental | Intravenous Infusion at the rate of 8 mg/kg of the patient's weight every 14 days. Receives: Biological: LYN00101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve after single dose use
Area under the concentration-time curve from 0 to ∞ with extrapolation of the final phase of the drug distribution
Measured: up to 14 days
Peak plasma concentration after single dose use
Peak plasma concentration (Cmax) of T1h
Measured: up to 14 days
Area under the plasma concentration after single - dose use
Area under the plasma concentration versus time curve( AUC(0-t)) of T1Hh
Measured: up to 14 days
Elimination rate constant after single - dose use
Elimination rate constant of T1h
Measured: up to 14 days
Time to peak after single dose use
Time to peak(Tmax) of T1h
Measured: up to 14 days
Half time after single dose use
Half time (t1/2) of T1h
Measured: up to 14 days
volume of distribution after single - dose use
Apparent VD - volume of distribution of T1h
Measured: up to 14 days
Total body clearance after single-dose use
Total body clearance (CLs)of T1h
Measured: up to 14 days
Mean residence time after single-dose use
MRT - Mean residence time of T1h
Measured: up to 14 days
Time to peak after Each Subsequent Introduction (multiple dose)
Time to peak(Tmax) of T1h
Measured: up to 24 weeks
Elimination rate constant after Each Subsequent Introductions (multiple dose)
Elimination rate constant of T1h
Measured: up to 24 weeks
Area under the plasma concentration versus time curve after Each Subsequent Introduction (multiple dose)
Area under the plasma concentration versus time curve( AUC(0-t)) of T1Hh
Measured: up to 24 weeks
Cmax of T1h after Each Subsequent Introduction (multiple dose)
Peak plasma concentration (Cmax) of T1h
Measured: up to 24 weeks
AUC(0-∞) of T1h after Each Subsequent Introduction (multiple dose)
Area under the plasma concentration versus time curve(AUC(0-∞))of T1h
Measured: up to 24 weeks
Secondary outcomes (8)
Average plasma concentration after Each Subsequent Introduction (multiple dose)
Average plasma concentration in steady state/Css_avg/ of T1h
Measured: up to 24 weeks
Vss of T1h after Each Subsequent Introduction (multiple dose)
Apparent volume of distribution in steady state /Vss/ of T1h
Measured: up to 24 weeks
CT or MRI or PET/CT Control
Tumor Necrosis and Dynamic of the Treatment ( by CT or MRI or PET/CT)
Measured: after 8 weeks
Area under the plasma concentration after each subsequent introduction (multiple dose)
Area under the plasma concentration versus time curve in steady state (AUCss) of T1h
Measured: up to 24 weeks
Blood C-reactive protein level after Each Subsequent Introduction (multiple dose)
C-reactive protein/CARP/
Measured: up to 24 weeks
Blood Test / morphology after Each Subsequent Introduction (multiple dose)
Blood Test / morphology
Measured: every week (up to 24 weeks)
TNF-α level after Each Subsequent Introduction (multiple dose)
Tumor Necrosis Factor -alpha (TNF-α)
Measured: up to 24 weeks
PGA after Each Subsequent Introduction (multiple dose)
Physician's Global Assessment /PGA/
Measured: every week up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2018
- Study start3 Apr 2019
- Primary completionJun 2020 (estimated)
- Study completionAug 2020 (estimated)
Why it stopped: Unable to recruit individuals for the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lynkcell Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03644459
- Sponsor's protocol ID
- LY233-234V
- Status last verified
- Mar 2020
- First submitted
- 3 Aug 2018
- Last updated
- 11 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03644459
- Acronym / sponsor ID
- LY233-234V
- Conditions
- Ovarian Cancer, Cervical Cancer, Colorectal Cancer, Stomach Cancer
- Keywords
- Tolerability, Safety, Humanized Anti-VEGF Monoclonal Antibody, autocrine loops, LYN00101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to recruit individuals for the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Lynkcell Inc.University, hospital or other
- Study start
- 3 Apr 2019 (actual)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 23 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LYN00101 | Experimental | Biological: LYN00101Intravenous Infusion at the rate of 8 mg/kg of the patient's weight every 14 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LYN00101Concentrate 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. | Biological | LYN00101 |
Primary outcome
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
Peak plasma concentration after single dose use
Time frame: up to 14 days
Peak plasma concentration (Cmax) of T1h
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
Elimination rate constant after single - dose use
Time frame: up to 14 days
Elimination rate constant of T1h
Time to peak after single dose use
Time frame: up to 14 days
Time to peak(Tmax) of T1h
Half time after single dose use
Time frame: up to 14 days
Half time (t1/2) of T1h
volume of distribution after single - dose use
Time frame: up to 14 days
Apparent VD - volume of distribution of T1h
Total body clearance after single-dose use
Time frame: up to 14 days
Total body clearance (CLs)of T1h
Mean residence time after single-dose use
Time frame: up to 14 days
MRT - Mean residence time of T1h
Time to peak after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
Time to peak(Tmax) of T1h
Elimination rate constant after Each Subsequent Introductions (multiple dose)
Time frame: up to 24 weeks
Elimination rate constant of T1h
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
Cmax of T1h after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
Peak plasma concentration (Cmax) of T1h
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
8 secondary outcomes
Average plasma concentration after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
Vss of T1h after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
CT or MRI or PET/CT Control
Time frame: after 8 weeks
Area under the plasma concentration after each subsequent introduction (multiple dose)
Time frame: up to 24 weeks
Blood C-reactive protein level after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
Blood Test / morphology after Each Subsequent Introduction (multiple dose)
Time frame: every week (up to 24 weeks)
TNF-α level after Each Subsequent Introduction (multiple dose)
Time frame: up to 24 weeks
PGA after Each Subsequent Introduction (multiple dose)
Time frame: every week up to 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LYN00101 in people with Ovarian Cancer and Cervical Cancer, run by Lynkcell Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration-time curve after single dose use (time frame: up to 14 days). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2020.