A Phase Ia, Dose Escalation Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in Patients With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This study is to assess the safety, tolerability and pharmacokinetics of single dose and multiple doses of humanized anti-VEGF monoclonal antibody (Sevacizumab) in patients with advanced or metastatic solid tumors. The secondary objective is to explore the preliminary anti-tumor effects.

Official Title
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A Phase Ia, Dose Escalation Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: Sevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced or metastatic malignant solid tumors; Patients failed the standard anti-tumor therapy or don't have standard regimen; At least one measurable lesion; At least 4 weeks from the last chemotherapy, 6 weeks from mitomycin, and nitrosourea treatment. If patients received anti-tumor biological products, at least four t1/2 of washout period is needed; Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0); ECOG performance status 0-1; Life expectancy ≥ 3 months; Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion allowed), PLT ≥ 100 × 10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN, TBIL ≤ 3 × ULN); Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN; Patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose. Exclusion Criteria: HCV, TP or HIV antibody positive; Previously received anti-VEGF protein drugs, such as bevacizumab; Histologically proven squamous cell lung cancer or squamous cell carcinoma of the head and neck; Active hepatitis B infection; Evidence of serious infection; Symptomatic brain metastases; Patients with proteinuria at screening (urine protein ≥ 1+); History of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment; Serious non-healing wounds, ulcers or fractures; Major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment; Active bleeding within 3 months prior to enrollment; Bleeding diathesis or coagulation disorder; History of arterial or venous thrombosis; History of myocardial infarction or stroke within 6 months prior to enrollment; Unstable angina, congestive heart failure, New York Heart Association (NYHA) class II heart failure, uncontrollable arrhythmia, uncontrolled hypertension (systolic blood pressure> 150 mmHg and/or diastolic blood pressure> 100 mmHg); Pregnant and lactating women; Known allergies to any excipient in the study drug; Patients with alcohol or drug dependence; Participation in other clinical trials within 4 weeks before enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevacizumab<br>2mg/kg、5mg/kg、7.5mg/kg、10mg/kg、12.5mg/kg、or 15mg/kg. d1, d29, d43, d57 | Drug: Sevacizumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) |  | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57 | 
| tmax |  | d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57 | 
| AUC |  | d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57 | 
| t1/2 |  | d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57 | 
| Objective Response Rate (ORR) |  | d29, d86 | 
| Disease Control Rate (DCR) |  | d29, d86 |