Clinical Trials List
Protocol NumberHLX55-001
2019-09-01 - 2022-08-31
Phase I
Recruiting4
ICD-10C7A.00
Malignant carcinoid tumor of unspecified site
A PHASE 1 DOSE FINDING/EXPANSION STUDY OF HLX55, A MONOCLONAL ANTIBODY TARGETING TYROSINEPROTEIN KINASE MET (C-MET) IN PATIENTS WITH ADVANCED SOLID TUMORS REFRACTORY TO STANDARD THERAPY
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Trial Applicant
A2 HEALTHCARE TAIWAN CORPORATION
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Sponsor
HENLIUS BIOTECH CO., LTD.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yao-Yu Hsieh Division of Hematology & Oncology
- Wei-Hong Cheng Division of Hematology & Oncology
- Tsu-Yi Chao Division of Hematology & Oncology
- HUI-WEN LIU Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳宇欽 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- 蔡文銓 Division of Others
- 黃子權 Division of Hematology & Oncology
- 賴學緯 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Han-Lin Hsu Division of Thoracic Medicine
- Tzu-I Wu Division of Obstetrics & Gynecology
- Ming-Hung Hu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
solid tumor
Objectives
Primary objective
For Stage 1: Dose finding stage
To identify safety, the maximum tolerated dose (MTD) and recommended phase 2
dose (RP2D) of HLX55 in patients with advanced or metastatic tumours refractory
to standard therapy.
For Stage 2: Dose expansion stage
To investigate the efficacy and safety of HLX55 in patients with advanced or
metastatic tumors with histologically confirmed c-MET mutations or
amplifications or over-expression and refractory to standard therapy.
Secondary objectives
For both stage 1 and stage 2
The pharmacokinetics (PK) of HLX55 at different dose levels or cohorts in
patients.
Changes in serum concentration of Hepatocyte growth factor (HGF) as a surrogate
pharmacodynamic biomarker of HLX55.
The immunogenicity of HLX55 in human beings.
Test Drug
HLX55
Active Ingredient
Humanized IgG2 monoclonal antibody targeting tyrosine-protein kinase Met (c-MET)
Dosage Form
Injection
Dosage
100 mg/vial
Endpoints
Primary outcome
For Stage 1: Dose finding stage
Numbers and percentage of patients with adverse events (AEs).
The maximum tolerated dose and recommended phase 2 dose (RP2D) of HLX55.
For Stage 2: Dose expansion stage
Numbers and percentage of patients with adverse events (AEs).
Disease control rate (DCR).
Overall response rate (ORR).
Duration of response (DOR).
Secondary outcome (for both stages)
PK profile of HLX55 including maximum concentration (Cmax), minimum
concentration (Cmin), area under concentration (AUC0-tau), half-life (T1/2), clearance
(CL) rate and the volume of distribution at steady state (Vss) of HLX55.
Changes in serum HGF levels before and at different time-points after HLX55
treatment.
The presence and percentage of anti-HLX55 antibody-positive patients
(immunogenicity)
For Stage 1: Dose finding stage
Numbers and percentage of patients with adverse events (AEs).
The maximum tolerated dose and recommended phase 2 dose (RP2D) of HLX55.
For Stage 2: Dose expansion stage
Numbers and percentage of patients with adverse events (AEs).
Disease control rate (DCR).
Overall response rate (ORR).
Duration of response (DOR).
Secondary outcome (for both stages)
PK profile of HLX55 including maximum concentration (Cmax), minimum
concentration (Cmin), area under concentration (AUC0-tau), half-life (T1/2), clearance
(CL) rate and the volume of distribution at steady state (Vss) of HLX55.
Changes in serum HGF levels before and at different time-points after HLX55
treatment.
The presence and percentage of anti-HLX55 antibody-positive patients
(immunogenicity)
Inclution Criteria
1. Eligible patients must be 18-years of age or older (or per local regulations) and ≦75 years of age.
2. For dose finding stage: patients with measurable or evaluable advanced or metastatic solid tumours who have failed standard therapy or for whom no standard therapy is available.
3. For dose expansion stage: patients with measurable or evaluable advanced or metastatic solid tumors with histologically confirmed c-MET mutations (MET exon 14 mutations) or amplifications (MET/CEP7 ratio ≥ 2.0 or MET ≥ 5.0 copies) or over-expression (immunohistochemistry [IHC] score ≥ 2+) and have failed standard therapy or for whom no standard therapy is available. Positive c-MET mutation/amplification/over-expression results should be available before the subject can receive HLX55.
4. No prior therapy with MET-targeting biological agents (patients who have received prior therapy with a MET-targeting tyrosine kinase inhibitor [TKI] is allowed.)
5. Must be able to supply adequate tumor tissue. (Adequate tumor biopsy material means (1) newly biopsied or archival tissue biopsied within 60 days before the first dosing, (2) Biopsy materials should be adequate for biomarker analysis (c-MET/Kras/EGFR).
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
7. Able to provide informed consent.
8. A life expectancy longer than three months.
9. Adequate hematologic functions, as defined by absolute neutrophil counts ≥ 1500/mm3; a haemoglobin level ≥ 9 gm/dL; a platelet count ≥ 100,000/mm3 and an international normalized ratio ≤ 1.5.
10. An adequate hepatic function defined by a total bilirubin level ≤ 1.5 x of ULN; aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x of ULN or ≤ 5 x of ULN in known hepatic metastases or with primary hepatocellular carcinoma.
11. Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula. In patients with extreme body weights (BMI < 18.5 OR > 30) estimated glomerular filtration rate (eGFR) ≥ 50ml/min/1.73m2 calculated by Modification of Diet in Renal Disease (MDRD) formula is acceptable.
12. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% measured by either cardiac echo or multigated acquisition (MUGA) scan.
13. At least 21days from prior cytotoxic chemotherapy, prior therapy with investigational small molecule agents (or medical device) or radiotherapy, at least 28 days from prior immunotherapy, biological agents or prior major surgery and at least 14 days from prior hormonal therapy and minor surgery before infusion of first dose of HLX55.
14. For patients with hepatocellular carcinoma, their Child-Pugh score must be A.
15. Able to be followed up as required by the study protocol.
16. Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential.
17. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for at least 180 days after last dose of study drug.
2. For dose finding stage: patients with measurable or evaluable advanced or metastatic solid tumours who have failed standard therapy or for whom no standard therapy is available.
3. For dose expansion stage: patients with measurable or evaluable advanced or metastatic solid tumors with histologically confirmed c-MET mutations (MET exon 14 mutations) or amplifications (MET/CEP7 ratio ≥ 2.0 or MET ≥ 5.0 copies) or over-expression (immunohistochemistry [IHC] score ≥ 2+) and have failed standard therapy or for whom no standard therapy is available. Positive c-MET mutation/amplification/over-expression results should be available before the subject can receive HLX55.
4. No prior therapy with MET-targeting biological agents (patients who have received prior therapy with a MET-targeting tyrosine kinase inhibitor [TKI] is allowed.)
5. Must be able to supply adequate tumor tissue. (Adequate tumor biopsy material means (1) newly biopsied or archival tissue biopsied within 60 days before the first dosing, (2) Biopsy materials should be adequate for biomarker analysis (c-MET/Kras/EGFR).
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
7. Able to provide informed consent.
8. A life expectancy longer than three months.
9. Adequate hematologic functions, as defined by absolute neutrophil counts ≥ 1500/mm3; a haemoglobin level ≥ 9 gm/dL; a platelet count ≥ 100,000/mm3 and an international normalized ratio ≤ 1.5.
10. An adequate hepatic function defined by a total bilirubin level ≤ 1.5 x of ULN; aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x of ULN or ≤ 5 x of ULN in known hepatic metastases or with primary hepatocellular carcinoma.
11. Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula. In patients with extreme body weights (BMI < 18.5 OR > 30) estimated glomerular filtration rate (eGFR) ≥ 50ml/min/1.73m2 calculated by Modification of Diet in Renal Disease (MDRD) formula is acceptable.
12. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% measured by either cardiac echo or multigated acquisition (MUGA) scan.
13. At least 21days from prior cytotoxic chemotherapy, prior therapy with investigational small molecule agents (or medical device) or radiotherapy, at least 28 days from prior immunotherapy, biological agents or prior major surgery and at least 14 days from prior hormonal therapy and minor surgery before infusion of first dose of HLX55.
14. For patients with hepatocellular carcinoma, their Child-Pugh score must be A.
15. Able to be followed up as required by the study protocol.
16. Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential.
17. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for at least 180 days after last dose of study drug.
Exclusion Criteria
1. Patients who still have ≥ grade 2 toxicities from prior therapies.
2. Concurrent unstable or uncontrolled medical conditions with either of the followings:
(1) Active systemic infections requiring intravenous antibiotic use within 1 week;
(2) Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;
(3) Clinically significant arrhythmia requiring anti-arrhythmia therapy, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association [NYHA]) or acute myocardial infarction within 6 months;
(4) Uncontrolled diabetes or poor compliance with hypoglycemics defined by glycated hemoglobin (HbA1c) ≥ 9.5%;
(5) The presence of chronically unhealed wound or ulcers;
(6) Uncontrolled hypercalcemia (defined as persistent Ionized (free) Calcium ≥ 6.5 mg/dl despite appropriate management.)
(7) Other chronic diseases, which, in the opinion of the investigator, could compromise the safety of the patient or the integrity of the study.
3. 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 at least 14 days before infusion of the first dose of HLX55 can be allowed in the study). Anticonvulsants are allowed.
4. 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 can participate).
5. Known history of human immunodeficiency virus infection (HIV), hepatitis B virus carrier status (HBV surface antigen positive) and hepatitis C carrier (anti-HCV antibody positive).
6. The patient is the investigator, sub-investigator or anyone directly involved in the conduct of the study.
7. History or current evidence of any condition or disease that could confound the results of the study or, in the opinion of Investigator(s), is not in the best interest of the patient to participate.
2. Concurrent unstable or uncontrolled medical conditions with either of the followings:
(1) Active systemic infections requiring intravenous antibiotic use within 1 week;
(2) Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;
(3) Clinically significant arrhythmia requiring anti-arrhythmia therapy, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association [NYHA]) or acute myocardial infarction within 6 months;
(4) Uncontrolled diabetes or poor compliance with hypoglycemics defined by glycated hemoglobin (HbA1c) ≥ 9.5%;
(5) The presence of chronically unhealed wound or ulcers;
(6) Uncontrolled hypercalcemia (defined as persistent Ionized (free) Calcium ≥ 6.5 mg/dl despite appropriate management.)
(7) Other chronic diseases, which, in the opinion of the investigator, could compromise the safety of the patient or the integrity of the study.
3. 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 at least 14 days before infusion of the first dose of HLX55 can be allowed in the study). Anticonvulsants are allowed.
4. 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 can participate).
5. Known history of human immunodeficiency virus infection (HIV), hepatitis B virus carrier status (HBV surface antigen positive) and hepatitis C carrier (anti-HCV antibody positive).
6. The patient is the investigator, sub-investigator or anyone directly involved in the conduct of the study.
7. History or current evidence of any condition or disease that could confound the results of the study or, in the opinion of Investigator(s), is not in the best interest of the patient to participate.
The Estimated Number of Participants
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Taiwan
60 participants
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Global
118 participants
