A Study of HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2 in Patients With Advanced Solid Tumors

• Status: Terminated
• Trial end date: 2019-05-30
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of fully human anti-VEGFR2 monoclonal antibody, HLX06, in patients with advanced or metastatic tumors refractory to standard therapy. This study will also evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of HLX06 and explore the potential prognostic and predictive biomarkers.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Henlix, Inc
• Treatments: Antibodies; Antibodies, Monoclonal; Endothelial Growth Factors; Immunoglobulins; Mitogens

Criteria

Inclusion Criteria:

1. Histologically-confirmed, unidimensionally-measurable and/or evaluable carcinoma which has failed standard therapy or for whom no standard therapy is available.

2. ECOG performance status score of ≤ 2 at study entry.

3. Able to provide written informed consent.

4. Adequate hematologic functions, as defined by: absolute neutrophil counts ≥ 1500/mm3; a hemoglobin level ≥ 10 gm/dL; a platelet count ≥ 100,000/mm3.

5. Adequate hepatic function defined by: a total bilirubin level ≤ 1.5x of upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5x of ULN or ≤ 5x of ULN in known hepatic metastases or with primary hepatocellular carcinoma.

6. Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula.

7. Adequate cardiac function defined as left ventricular ejection fraction (LVEF)≥ 50%.

8. Use of effective contraceptive measures if procreative potential exists.

9. At least 28 days from prior major surgery, prior cytotoxic chemotherapy, or prior therapy with investigational agents (or medical device) or local radiotherapy before 1st infusion of HLX06.

10. For patients with hepatocellular carcinoma, their Child-Pugh score has to be A.

11. Able to be followed up as required by the study protocol.

Exclusion Criteria:

1. Patients with large centrally located pulmonary lesions adjacent to or invading large blood vessels.

2. Hemoptysis more than ½ teaspoon (approximately 2-3 mL) of red blood per day.

3. Patients who still have ≥ grade 2 toxicities from prior therapies.

4. Concurrent unstable or uncontrolled medical conditions with either of the followings:

• Active systemic infections;

• Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;

• Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association [NYHA]) or acute myocardial infarction within 6 months;

• 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.

5. 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.

6. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 3 years are allowed to participate).

7. Pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast-feeding (for female patients only).

8. A known history or clinical evidence of a deep vein or arterial thrombosis, or pulmonary embolism within 6 months of first infusion of HLX06.

9. Less than six weeks from last infusion of ramucirumab, or any other anti-VEGF monoclonal antibody therapy (Last treatment with other monoclonal antibodies targeting proteins other than anti-angiogenic factors is permitted if ≥ 4 weeks prior to the first infusion of HLX06).

10. Proteinuria ≥ 2+ in routine urinalysis (patients with a protein value of ≤500 mg confirmed by a 24-hour urine collection are eligible).

11. Known history of human immunodeficiency virus infection (HIV).

12. The patient is the investigator, sub-investigator or any one directly involved in the conduct of the study.