None listed
Conditions
Brief summary
This is a study evaluating the safety and maximum tolerated dose of HLX20, a Human Monoclonal Antibody, in participants with advanced or metastatic solid tumours. Who is it for? You may be eligible for this study if you are aged at least 18 years old and have a confirmed advanced or metastatic tumour, for which treatment has failed or not tolerated. Study details All participants in the study will receive intravenous treatment with the study drug HLX20. The dose may vary depending on when the participant joins the study. Blood and tissue samples will be collected for safety analysis, efficacy and tolerability of HLX20. Additionally, patients may also undergo imaging/scans and a biopsy if archival tissue sample is unavailable. There is no guarantee that you will receive any benefits from this study, and taking part in this study may or may not cause your health to improve. Information from this study may help doctors learn more about HLX20 on the treatment of your cancer
Interventions
HLX20 is a recombinant human IgG4 monoclonal antibody directed against human PD-L1.
The treatment is divided into cycles. Each cycle of treatment is 4 weeks with no break between cycles. HLX20 will be administered as a single infusion every fortnight on Days 1 and 15 of a 28 day (4 week) cycle. The IV infusion will be delivered over 60 ± 10 minutes and will be followed by a 30 minute observation period.
The 4 planned dose levels (cohorts) to be tested are 1, 3, 10, and 20 mg/kg. The dose level
HLX20 is a recombinant human IgG4 monoclonal antibody directed against human PD-L1. The treatment is divided into cycles. Each cycle of treatment is 4 weeks with no break between cycles. HLX20 will be administered as a single infusion every fortnight on Days 1 and 15 of a 28 day (4 week) cycle. The IV infusion will be delivered over 60 ± 10 minutes and will be followed by a 30 minute observation period. The 4 planned dose levels (cohorts) to be tested are 1, 3, 10, and 20 mg/kg. The dose level for a cohort may be adjusted, although the dose cannot be more than 20 mg/kg HLX20. The Safety Monitoring Committee, will conduct the safety data review of each cohort and will approve the subsequent dose escalation or de-escalation in the study. Enrolment of the next higher dose cohort will be initiated only after the verified safety data for the 4-week dose-limiting toxicity (DLT) period has been reviewed by the Safety Monitoring Committee. Each participant will continue on the same dose level through the study unless the safety monitoring committee deems the dose to be reduced. The total study duration per patient is variable. Screening will be up to 28 days before the first infusion. The maximum duration of HLX20 administration to an individual patient in this study is 1 year. All patients will be followed up from the last dose of HLX20 for up to 90 days until relapse, initiation of a new therapy, or until prior toxicities less than or equal to Grade 1 or stabilized.
Sponsors
Shanghai Henlius Biotech, Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or females of 18 years of age or older 2. Have histologically-proven measurable, or evaluable advanced (systemically or locally progressive), or metastatic solid tumours or the locally advanced disease is not amenable to local therapy, who have failed, or are intolerant to standard therapy or for whom no standard therapy is available. (For patients with hepatocellular carcinoma, the diagnosis needs to be supported by dynamic computed tomography [CT]/magnetic resonance imaging, if pathological confirmation is not attainable). 3. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 at the time of study entry. 4. Able to comprehend and provide informed consent. 5. A life expectancy longer than 3 months in the opinion of the Investigator. 6. Adequate hematologic functions, as defined by: absolute neutrophil counts >= 1500/mm3; a hemoglobin level >= 10 g/dL; a platelet count >= 100,000/mm3. 7. Adequate hepatic function defined by: a total bilirubin level <=1.5 × of upper limit of normal (ULN); aspartate transaminase and alanine transaminase levels<= 2.5 × ULN or <= 5 × ULN in known hepatic metastases or with primary hepatocellular carcinoma. 8. Adequate renal function, as defined by the creatinine clearance >= 50 mL/minute (as calculated by the Cockcroft-Gault formula). 9. Adequate cardiac function defined as left ventricular ejection fraction >= 50% by cardiac ultrasound or multigated acquisition (MUGA) scan. A recent MUGA scan is acceptable if performed within 8 weeks of the first infusion of IP. 10. Females of child-bearing potential must have a negative pregnancy test upon entry into this study and must be willing to use highly effective birth control upon enrollment, during the Treatment Phase and for 180 days following the last dose of study drug. A female is considered of child-bearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 11. If male, must be surgically sterile or willing to use highly effective birth control upon enrollment, during the Treatment Phase, and for 180 days following the last dose of study drug. 12. History of prior major surgery, prior cytotoxic chemotherapy, or prior therapy with investigational agents, medical device, or local radiotherapy should be at least > =28 days prior to Screening and at least >= 42 days from the last infusion of immune check point inhibitors (including anti-programmed cell death receptor-1 [PD-1] or anti-PD-L1) before the first infusion of IP. 13. Child-Pugh score of A (patients with hepatocellular carcinoma only). 14. Able to be followed up as required by the study protocol.
Exclusion criteria
The following are the main exclusion criteria: 1. Persistent >= Grade 2 toxicities from prior therapies, with the exception of alopecia of any grade, Grade <= 2 peripheral neuropathy, and laboratory values listed per the inclusion criteria. 2. Concurrent unstable or uncontrolled medical conditions, including: • Active systemic infections; • Poorly controlled hypertension (systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg), or poor compliance with antihypertensive agents; • Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (Class III or IV of New York Heart Association) or acute myocardial infarction within 6 months; • Uncontrolled diabetes or poor compliance with hypoglycemic agents; • 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 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 be taking steroids for brain edema). Anticonvulsants are allowed. Patients with history of leptomeningeal disease will be excluded. 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). 5. Females who are pregnant, lactating, or intend to become pregnant during their participation in this study. 6. Known history of human immunodeficiency virus infection. 7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease, Wegner syndrome) within the past 2 years. Patients with well controlled vitiligo, alopecia, and Grave’s disease, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 3 years), or patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen are not excluded. 8. Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection), OR • systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, OR • steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 9. History of primary immunodeficiency or allogeneic transplantation. 10. Active hepatitis B (HBsAg reactive). Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at Screening. 11. History of interstitial lung disease. 12. Receipt of live attenuated vaccines within 30 days prior to the first dose of IP. Patients, if enrolled, should not receive live or live attenuated vaccines during the study and for 30 days after the last dose of IP. 13. The patient is the Investigator, sub-investigator or anyone directly involved in the conduct of the study. 14. History or current evidence of any condition or disease that could confound the results of the study or, in the opinion of Investigator, is not in the best interest of the patient to participate.
Outcome results
None listed