A Study of Anti-VEGF Monoclonal Antibody hPV19 in Patients With Solid Tumors

A Phase Ib Study of hPV19, a Novel Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF),in Combination With Chemotherapy in Patients With Advanced Solid Tumors Refractory to Standard Therapy.

hPV19 is a monoclonal antibody (mAb) directed against vascular endothelial growth factor (VEGF). hPV19 binds to human VEGF with unique binding site on VEGF different from that of Bevacizumab(Avastin) and inhibits the binding of VEGF to it's receptors, VEGF-R1 and VEGF-R2. By preventing VEGF binding to its receptors, growth of tumor blood vessels are inhibited and tumor growth prevented or slowed. In this study we are investigating the tolerability, safety, pharmacokinetics and anti-tumor activity of hPV19 in combination with chemotherapy in patients with solid tumors. hPV19 will give to patients by intravenous(i.v.) infusion with a single and multiple doses.

Study Overview

• Status: Unknown
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: hPV19 mAb; Biological: hPV19 mAb; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Paclitaxel; Drug: Carboplatin; Drug: Carboplatin; Drug: Gemcitabine; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed malignity
• Measurable disease
• Performance status 2 or less(ECOG)
• Life expectancy ≥3 months

Exclusion Criteria:

• hepatitis C virus (HCV), or HIV antibody positive
• Previously received anti-VEGF mAb or fusion-protein drugs within 28 days nearly
• Evidence of serious infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1; hPV19 mAb plus FOLFOX(5-Fluorouracil,Oxaliplatin,Leucovorin)	Biological: hPV19 mAb; Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks; Other Names: anti-VEGF mAb; Biological: hPV19 mAb; Intravenous (IV) infusions, 6 milligrams per kilogram (mg/kg) every 3 weeks; Other Names: anti-VEGF mAb; Drug: 5-Fluorouracil; 400 mg/m2 bolus followed by a 2400 mg/m2 continuous infusion, every 2 weeks; Drug: Oxaliplatin; IV Infusion, 85 milligrams per square meter (mg/m2) every 2 weeks; Drug: Leucovorin; IV infusion, 400 mg/m2 every 2 weeks
Experimental: group 2; hPV19 mAb plus paclitaxel/carboplatin	Biological: hPV19 mAb; Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks; Other Names: anti-VEGF mAb; Biological: hPV19 mAb; Intravenous (IV) infusions, 6 milligrams per kilogram (mg/kg) every 3 weeks; Other Names: anti-VEGF mAb; Drug: Paclitaxel; IV infusion, 175 mg/m2 every 3 weeks; Drug: Carboplatin; IV infusion, AUC=6 every 3 weeks; Drug: Carboplatin; IV infusion, AUC=4 every 3 weeks
Experimental: group 3; hPV19 mAb plus gemcitabine/carboplatin	Biological: hPV19 mAb; Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks; Other Names: anti-VEGF mAb; Biological: hPV19 mAb; Intravenous (IV) infusions, 6 milligrams per kilogram (mg/kg) every 3 weeks; Other Names: anti-VEGF mAb; Drug: Carboplatin; IV infusion, AUC=6 every 3 weeks; Drug: Carboplatin; IV infusion, AUC=4 every 3 weeks; Drug: Gemcitabine; IV infusion, 1000 mg/m2 at day1 and day 8 every 3 weeks
Experimental: group 4; hPV19 mAb plus FOLFIRI(5-Fluorouracil,Irinotecan, Leucovorin)	Biological: hPV19 mAb; Intravenous (IV) infusions, 4 and 6 milligrams per kilogram (mg/kg) every 2 weeks; Other Names: anti-VEGF mAb; Biological: hPV19 mAb; Intravenous (IV) infusions, 6 milligrams per kilogram (mg/kg) every 3 weeks; Other Names: anti-VEGF mAb; Drug: 5-Fluorouracil; 400 mg/m2 bolus followed by a 2400 mg/m2 continuous infusion, every 2 weeks; Drug: Leucovorin; IV infusion, 400 mg/m2 every 2 weeks; Drug: Irinotecan; IV Infusion,180 milligrams per square meter (mg/m2) every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period	DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03) with any one of the following: Grade 4 neutropenia ≥7 days; febrile neutropenia; grade 4 anemia; grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding;; ≥ grade 3 nonhematologic toxicity with the exception of nausea, vomiting, diarrhea, dehydration or electrolyte abnormalities that resolved to a lower grade with maximum supportive treatment within 3 days;; ≥Grade 3 hypertension that cannot resolved to a lower grade with supportive treatment within 2 weeks or uncontrolled hypertension;; Urine protein ≥3.5 grams/24 hours and cannot resolved to < 1.0 grams/24 hours within 2 weeks;; Gastrointestinal perforation: symptoms, signs and imaging evidence of abdominal pain require surgical treatment;; Grade 3 or 4 arterial thromboembolism, including stroke and myocardial infarction;	during the first 21 days
Number of Participants With hPV19 Drug-Related Adverse Events or Serious Adverse Events	Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to hPV19. Events related to chemotherapy were reported separately.	Baseline to the last dose plus 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serum Anti-hPV19 Antibodies (Immunogenicity)		before Single dose; Day 21 of 21-day DLT assessment period; Every 8 or 9 weeks after 21-day DLT assessment period.
Maximum Concentration (Cmax) of hPV19		Single dose(Cycle 1)：2h before administered; after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.
Area Under the Curve (AUC) of hPV19		Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.
Half Life (t1/2) of hPV19	t1/2 is the time required for the plasma/serum concentration to decrease 50%	Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.
Clearance (CL) of hPV19		Single dose(Cycle 1)：2h before administered, after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.
Steady State Volume of Distribution (Vss) of hPV19	Vss is the theoretical volume in which the total amount of study drug would need to be uniformly distributed during steady state to produce the same concentration as it is in plasma/serum	Single dose(Cycle 1)：2h before administered; after administered 10min±5min、4h±30min、24h±1h、168h±1h、336h±1h. Other cycles: 2h before administered and after administration 10min±5min.
Best Overall Response [Anti-Tumor Activity of hPV19 Plus Chemotherapy]	Best overall response evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression). Stable Disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.	Up to six months after 1st treatment or until progression of disease (PD)

Collaborators and Investigators

• Sponsor: SuZhou Stainwei Biotech Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2018
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: VEGF; antibody; phase1; mAb
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Gemcitabine; Carboplatin; Paclitaxel; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: STW201701B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No