Solid Tumor, AdultPhase 1NCT03494231
A Study of HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2 in Patients With Advanced Solid Tumors
A Phase 1 study testing HLX06 in people with Solid Tumor, Adult, run by Henlix, Inc at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult
- What is being tested?
- HLX06
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteTaiwan
- Study dates
- 22 Mar 2018to 30 May 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically-confirmed, unidimensionally-measurable and/or evaluable carcinoma which has failed standard therapy or for whom no standard therapy is available.
- ECOG performance status score of ≤ 2 at study entry.
- Able to provide written informed consent.
- Adequate hematologic functions, as defined by: absolute neutrophil counts ≥ 1500/mm3; a hemoglobin level ≥ 10 gm/dL; a platelet count ≥ 100,000/mm3.
- 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.
- Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula.
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- Adequate cardiac function defined as left ventricular ejection fraction (LVEF)≥ 50%.
- Use of effective contraceptive measures if procreative potential exists.
- 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.
- For patients with hepatocellular carcinoma, their Child-Pugh score has to be A.
- Able to be followed up as required by the study protocol.
Who cannot join
- Patients with large centrally located pulmonary lesions adjacent to or invading large blood vessels.
- Hemoptysis more than ½ teaspoon (approximately 2-3 mL) of red blood per day.
- Patients who still have ≥ grade 2 toxicities from prior therapies.
- 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;
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- 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.
- 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.
- 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).
- 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 within 6 months of first infusion of HLX06.
- 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).
- Proteinuria ≥ 2+ in routine urinalysis (patients with a protein value of ≤500 mg confirmed by a 24-hour urine collection are eligible).
- Known history of human immunodeficiency virus infection (HIV).
- The patient is the investigator, sub-investigator or any one directly involved in the conduct of the study.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Taipei Medical University-Shuang Ho Hospital
New Taipei City, 23561
About this study
Official title: An Open-label, Dose Escalation Phase 1 Study to Investigate HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2, in Patients With Advanced Solid Tumors Refractory to Standard Therapy
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.
Read the detailed description
Angiogenesis plays an important role in cancer development. The VEGF family and their receptors (VEGFR) are well characterized for their role in neoplastic angiogenesis. VEGFR2 belongs to type V receptor tyrosine kinase encoded by KDR gene, and is expressed in vascular endothelial cells. It is a primary responder to vascular endothelial growth factor signal that regulates endothelial migration and proliferation. The expression of VEGFR2 can be found in multiple tumor types, including angiosarcoma, Kaposi sarcoma. In epithelial carcinoma, VEGFR2 expression can be found in mesothelioma, non-small cell lung cancer, and embryonal carcinoma. Targeting angiogenesis using either small molecule inhibitors or biological agents have been widely used in current cancer management. Current approved anti-angiogenesis biological agents include bevacizumab, ramucirumab, aflibercept. Among them, ramucirumab (IMC-1121B) targets vascular endothelial growth factor receptor 2 (VEGFR2). Ramucirumab has been approved for use in combination with paclitaxel for second-line treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Although ramucirumab has been approved for gastric cancer, its improvement in overall survival is still not satisfactory. It prolongs the overall survival by 6 weeks when combined with paclitaxel. So far, there is not biomarker available to predict the efficacy of ramucirumab. Therefore, a new monoclonal antibody also targeting VEGFR2 might provide better efficacy for cancer patients.
HLX06 is a new, fully human monoclonal antibody targeting VEGFR2. It has better binding affinity to VEGFR2, and also binds to different region in VEGFR2. In vitro studies have demonstrated the growth inhibition of human endothelial cells, and HLX06 has shown growth inhibition of tumors in xenogeneic studies.
Nonclinical studies up to weekly 150 mg/kg in cynomolgus monkeys for 13 weeks have shown good tolerability without evident toxicities (please refer to Investigator's brochure). HLX06 shows cross-reactivity to both monkey and human VEGFR2, but does not bind rodent VEGFR2. The investigators expect that HLX06 will provide a better alternative than ramucirumab for patients with advanced cancers.
However, HLX06 has not yet been tested in humans. Therefore, the investigators propose this first-in-human phase 1 study. In this study, the investigators intend to monitor the safety and tolerability of HLX06 in humans, and hope to identify the maximum tolerated dose, and determine the recommended phase 2 dose for future study. At the same time, the investigators would like to collect information of the pharmacokinetics and pharmacodynamics of this drug and its potential immunogenicity.
To minimize the risk of patients who volunteer to receive this experimental drug, the investigators have selected 250 mg flat dose as the starting dose. The reason for using flat dosing instead of body weight-adjusted dosing is based on previous population pharmacokinetic studies for multiple monoclonal antibody drugs. The 500 mg flat dose was conservatively selected to provide sufficient safety factor in the FIH study, based on 1/6 of the human equivalent dose (1/3) of the highest non-severely toxic dose (HNSTD) in 3 month repeat-dose studies in cynomolgus monkeys.
To investigate the dose required to reach maximal effect, the investigators propose a dose escalation sequence. The purpose of the dose escalation is to obtain the pharmacokinetics and pharmacodynamics of HLX06 at different dose levels, and investigate its relationship with adverse reactions. Also, the investigators intend to identify the MTD. The information from the dose escalation is crucial to determine the optimal dose in future studies and potential indications for HLX06.
- Conditions
- Solid Tumor, Adult
- Being tested
- HLX06
- Keywords
- Metastatic, Refractory, Cancer, Solid, Tumor
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLX06Drug
Also called anti-VEGFR2 monoclonal antibody
recombinant fully human anti-VEGFR2 monoclonal antibody against cancers
| Study group | Role | What they receive |
|---|---|---|
| HLX06, in patients with solid cancers | Experimental | Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX06 once per week. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 500, 750, 900, 1200, 1500 mg, starting from 500 mg/kg. Receives: Drug: HLX06 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2018
- Study start22 Mar 2018
- Primary completion17 May 2019
- Study completion30 May 2019
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies 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
- Model description
- The modified accelerated titration design (ATD) 2A and Bayesian optimal interval design (BOIN)
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henlix, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tus-Yi Chao, MD, Principal investigator, Taipei Medical University Shuang Ho Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03494231
- Sponsor's protocol ID
- HLX06-001
- Status last verified
- Jul 2019
- First submitted
- 11 Mar 2018
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose Escalation Phase 1 Study to Investigate HLX06, a Humanized Monoclonal Antibody Targeting Human Vascular Endothelial Growth Factor Receptor-2, in Patients With Advanced Solid Tumors Refractory to Standard Therapy
- ClinicalTrials.gov ID
- NCT03494231
- Acronym / sponsor ID
- HLX06-001
- Conditions
- Solid Tumor, Adult
- Keywords
- Metastatic, Refractory, Cancer, Solid, Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Henlix, IncIndustry (pharma, biotech, devices)
- Study start
- 22 Mar 2018 (actual)
- Primary completion
- 17 May 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 11 Apr 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 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.
Detailed description
Angiogenesis plays an important role in cancer development. The VEGF family and their receptors (VEGFR) are well characterized for their role in neoplastic angiogenesis. VEGFR2 belongs to type V receptor tyrosine kinase encoded by KDR gene, and is expressed in vascular endothelial cells. It is a primary responder to vascular endothelial growth factor signal that regulates endothelial migration and proliferation. The expression of VEGFR2 can be found in multiple tumor types, including angiosarcoma, Kaposi sarcoma. In epithelial carcinoma, VEGFR2 expression can be found in mesothelioma, non-small cell lung cancer, and embryonal carcinoma. Targeting angiogenesis using either small molecule inhibitors or biological agents have been widely used in current cancer management. Current approved anti-angiogenesis biological agents include bevacizumab, ramucirumab, aflibercept. Among them, ramucirumab (IMC-1121B) targets vascular endothelial growth factor receptor 2 (VEGFR2). Ramucirumab has been approved for use in combination with paclitaxel for second-line treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Although ramucirumab has been approved for gastric cancer, its improvement in overall survival is still not satisfactory. It prolongs the overall survival by 6 weeks when combined with paclitaxel. So far, there is not biomarker available to predict the efficacy of ramucirumab. Therefore, a new monoclonal antibody also targeting VEGFR2 might provide better efficacy for cancer patients.
HLX06 is a new, fully human monoclonal antibody targeting VEGFR2. It has better binding affinity to VEGFR2, and also binds to different region in VEGFR2. In vitro studies have demonstrated the growth inhibition of human endothelial cells, and HLX06 has shown growth inhibition of tumors in xenogeneic studies.
Nonclinical studies up to weekly 150 mg/kg in cynomolgus monkeys for 13 weeks have shown good tolerability without evident toxicities (please refer to Investigator's brochure). HLX06 shows cross-reactivity to both monkey and human VEGFR2, but does not bind rodent VEGFR2. The investigators expect that HLX06 will provide a better alternative than ramucirumab for patients with advanced cancers.
However, HLX06 has not yet been tested in humans. Therefore, the investigators propose this first-in-human phase 1 study. In this study, the investigators intend to monitor the safety and tolerability of HLX06 in humans, and hope to identify the maximum tolerated dose, and determine the recommended phase 2 dose for future study. At the same time, the investigators would like to collect information of the pharmacokinetics and pharmacodynamics of this drug and its potential immunogenicity.
To minimize the risk of patients who volunteer to receive this experimental drug, the investigators have selected 250 mg flat dose as the starting dose. The reason for using flat dosing instead of body weight-adjusted dosing is based on previous population pharmacokinetic studies for multiple monoclonal antibody drugs. The 500 mg flat dose was conservatively selected to provide sufficient safety factor in the FIH study, based on 1/6 of the human equivalent dose (1/3) of the highest non-severely toxic dose (HNSTD) in 3 month repeat-dose studies in cynomolgus monkeys.
To investigate the dose required to reach maximal effect, the investigators propose a dose escalation sequence. The purpose of the dose escalation is to obtain the pharmacokinetics and pharmacodynamics of HLX06 at different dose levels, and investigate its relationship with adverse reactions. Also, the investigators intend to identify the MTD. The information from the dose escalation is crucial to determine the optimal dose in future studies and potential indications for HLX06.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The modified accelerated titration design (ATD) 2A and Bayesian optimal interval design (BOIN)
| Arm | Type | Receives |
|---|---|---|
| HLX06, in patients with solid cancers | Experimental | Drug: HLX06Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX06 once per week. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 500, 750, 900, 1200, 1500 mg, starting from 500 mg/kg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically-confirmed, unidimensionally-measurable and/or evaluable carcinoma which has failed standard therapy or for whom no standard therapy is available.
- ECOG performance status score of ≤ 2 at study entry.
- Able to provide written informed consent.
- Adequate hematologic functions, as defined by: absolute neutrophil counts ≥ 1500/mm3; a hemoglobin level ≥ 10 gm/dL; a platelet count ≥ 100,000/mm3.
- 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.
Key exclusion criteria (18 listed)
- Patients with large centrally located pulmonary lesions adjacent to or invading large blood vessels.
- Hemoptysis more than ½ teaspoon (approximately 2-3 mL) of red blood per day.
- Patients who still have ≥ grade 2 toxicities from prior therapies.
- Concurrent unstable or uncontrolled medical conditions with either of the followings:
- 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.
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 |
|---|---|---|
| HLX06Also: anti-VEGFR2 monoclonal antibodyrecombinant fully human anti-VEGFR2 monoclonal antibody against cancers | Drug | HLX06, in patients with solid cancers |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 1.5 years
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Individual participant dataSharing planned: Undecided
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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.
Tus-Yi Chao, MD principal investigator
Taipei Medical University Shuang Ho Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HLX06 in people with Solid Tumor, Adult, run by Henlix, Inc at 1 site in Taiwan.
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 18 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: stopped early, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
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 stopped early (reason given: Lack of efficacy). Results are not available in the source record.
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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 1.5 years). 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 30 Jul 2019.