Evaluate Safety, Tolerability and PK of HLX55 in Patients With Advanced Solid Tumors With Different cMET Status

NCT04169178 | Unknown Phase 1 DMC

• 1 other identifier: HLX55-001
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 4

Brief Summary

A mutilpe-center, open-label, dose-escalation Phase I clinical trial to evaluate the safety and the tolerability of HLX55 in patients with advanced solid tumors overexpressing/Mutation/Amplification cMET after failure of standard of care.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (6)

• Dose finding stage-safety

  Numbers and percentage of patients with adverse events (AEs).

  Up to 2 years

• Dose finding stage-MTD or RP2D

  The maximum tolerated dose and recommended phase 2 dose (RP2D) of HLX55.

  Up to 2 years

• Dose expansion stage-safety

  Numbers and percentage of patients with adverse events (AEs).

  Up to 2 years

• Dose expansion stage-efficacy

  Disease control rate (DCR).

  Up to 2 years

• Dose expansion stage-efficacy

  Overall response rate (ORR).

  Up to 2 years

• Dose expansion stage-efficacy

  Duration of response (DOR).

  Up to 2 years

Secondary Outcomes (3)

• Dose finding stage and dose expansion stage-PK profile

  Through study completion, up to 2 years.

• Dose finding stage and dose expansion stage-serum HGF levels

  Cycle 1 to 3 (each cycle is 21 days)

• Dose finding stage and dose expansion stage-immunogenicity

  Up to 2 years

Other Outcomes (1)

• Dose finding stage and dose expansion stage-cMET status

  up to 3 cycles (each cycle is 21 days)

Study Arms (5)

HLX55, dose finding stage, advanced solid tumor

EXPERIMENTAL

Participants will receive HLX55 at assign dose level, e.g. 2.5, 5, 15 and 25 mg/kg every three weeks followed by a 21-day DLT observation period.

Drug: HLX55

HLX55, dose expansion stage, gastric cancer

EXPERIMENTAL

Participants diagnosed with gastric cancer with will receive HLX55 in recommended phase 2 dose (RP2D) every three weeks.

Drug: HLX55

HLX55, dose expansion stage, NSCLC

EXPERIMENTAL

Participants diagnosed with non-small cell lung cancer (NSCLC) with will receive HLX55 in RP2D every three weeks.

Drug: HLX55

HLX55, dose expansion stage, colorectal cancer

EXPERIMENTAL

Participants diagnosed with colorectal cancer (CRC) with will receive HLX55 in RP2D every three weeks.

Drug: HLX55

HLX55, dose expansion stage, other solid cancer

EXPERIMENTAL

Participants diagnosed with other solid cancer with will receive HLX55 in RP2D every three weeks.

Drug: HLX55

Interventions

HLX55 DRUG

A humanized IgG2 monoclonal antibody targeting tyrosine-protein kinase MET (c-MET)

Also known as: HLX55 monoclonal antibody for Injection

HLX55, dose expansion stage, NSCLC; HLX55, dose expansion stage, colorectal cancer; HLX55, dose expansion stage, gastric cancer; HLX55, dose expansion stage, other solid cancer; HLX55, dose finding stage, advanced solid tumor

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients must be 18-years of age or older (or per local regulations) and ≦75 years of age.
• 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.
• 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.
• No prior therapy with MET-targeting biological agents (patients who have received prior therapy with a MET-targeting tyrosine kinase inhibitor \[TKI\] is allowed.)
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
• Able to provide informed consent.
• A life expectancy longer than three months.
• 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.
• An adequate hepatic function defined by a total bilirubin level ≤ 1.5 x of upper limit of normal values (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.
• Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula. In patients with extreme body weights (body mass index \[BMI\] \< 18.5 OR \> 30) estimated glomerular filtration rate (eGFR) ≥ 50ml/min calculated by Modification of Diet in Renal Disease (MDRD) formula is acceptable.
• Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% measured by either cardiac echo or multigated acquisition (MUGA) scan.
• 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.
• For patients with hepatocellular carcinoma, their Child-Pugh score must be A.
• Able to be followed up as required by the study protocol.

You may not qualify if:

• Patients who still have ≥ grade 2 toxicities from prior therapies.
• Concurrent unstable or uncontrolled medical conditions with either of the followings:
• Active systemic infections requiring intravenous antibiotic use within 1 week;
• Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;
• 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;
• Uncontrolled diabetes or poor compliance with hypoglycemics defined by glycated hemoglobin (HbA1c) ≥ 9.5%;
• The presence of chronically unhealed wound or ulcers;
• Uncontrolled hypercalcemia (defined as persistent Ionized (free) Calcium ≥ 6.5 mg/dl despite appropriate management.)
• Other chronic diseases, which, in the opinion of the investigator, could compromise the safety of the patient or the integrity of the 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 at least 14 days before infusion of the first dose of HLX55 can be allowed in the study). 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 can participate).
• 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).
• The patient is the investigator, sub-investigator or anyone directly involved in the conduct of the study.
• 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.

Sponsors & Collaborators

• Henlix, Inc: lead

Study Sites (4)

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, 114, Taiwan

RECRUITING

Taipei Minicipal Wangfang Hospital

Taipei, 116, Taiwan

RECRUITING

Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare

Taipei County, 235, Taiwan

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tsu-Yi Chao, MD. PhD.

  Shuang Ho Hospital,Ministry of Health and Welfare, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

• Ching-Liang Ho, MD

  Tri-Service General Hospital, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

• Wu-Chou Su, MD. PhD.

  National Cheng Kung University Hospital, Tainan, Taiwan

  PRINCIPAL INVESTIGATOR

• Chia-Lun Chang, MD

  Taipei Municipal Wanfang Hospital, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PeiZhi Lu

CONTACT

+886-2-792-7927; plu@henlix.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 19, 2019
• Study Start: March 3, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 1, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4)