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

NCT03644459 | Withdrawn Phase 1

• 1 other identifier: LY233-234V
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Keywords

Tolerability; Safety; Humanized Anti-VEGF Monoclonal Antibody; autocrine loops; LYN00101

Outcome Measures

Primary Outcomes (14)

• 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

  up to 14 days

• Peak plasma concentration after single dose use

  Peak plasma concentration (Cmax) of T1h

  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

  up to 14 days

• Elimination rate constant after single - dose use

  Elimination rate constant of T1h

  up to 14 days

• Time to peak after single dose use

  Time to peak(Tmax) of T1h

  up to 14 days

• Half time after single dose use

  Half time (t1/2) of T1h

  up to 14 days

• volume of distribution after single - dose use

  Apparent VD - volume of distribution of T1h

  up to 14 days

• Total body clearance after single-dose use

  Total body clearance (CLs)of T1h

  up to 14 days

• Mean residence time after single-dose use

  MRT - Mean residence time of T1h

  up to 14 days

• Time to peak after Each Subsequent Introduction (multiple dose)

  Time to peak(Tmax) of T1h

  up to 24 weeks

• Elimination rate constant after Each Subsequent Introductions (multiple dose)

  Elimination rate constant of T1h

  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

  up to 24 weeks

• Cmax of T1h after Each Subsequent Introduction (multiple dose)

  Peak plasma concentration (Cmax) of T1h

  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

  up to 24 weeks

Secondary Outcomes (8)

• Average plasma concentration after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

• Vss of T1h after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

• CT or MRI or PET/CT Control

  after 8 weeks

• Area under the plasma concentration after each subsequent introduction (multiple dose)

  up to 24 weeks

• Blood C-reactive protein level after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

Other Outcomes (3)

• CLs after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

• Apparent VD - volume of distribution of T1h after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

• Half time (t1/2) of T1h after Each Subsequent Introduction (multiple dose)

  up to 24 weeks

Study Arms (1)

LYN00101

EXPERIMENTAL

Intravenous Infusion at the rate of 8 mg/kg of the patient's weight every 14 days.

Biological: LYN00101

Interventions

LYN00101 BIOLOGICAL

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.

LYN00101

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Lynkcell Inc.: lead

MeSH Terms

Conditions

Ovarian Neoplasms; Uterine Cervical Neoplasms; Colorectal Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 23, 2018
• Study Start: April 3, 2019
• Primary Completion: June 1, 2020
• Study Completion: August 1, 2020
• Last Updated: March 11, 2020

Record last verified: 2020-03