The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03588650




Registration number
NCT03588650
Ethics application status
Date submitted
22/06/2018
Date registered
17/07/2018
Date last updated
4/09/2018

Titles & IDs
Public title
A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting PD-L1Protein in Patients With Advanced Solid Tumors
Scientific title
A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting Programmed Death Ligand 1 (PD-L1) Protein in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
HLX20-001
Universal Trial Number (UTN)
Trial acronym
HLX20
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HLX20

Experimental: HLX20, in patients with solid tumors - Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX20 once every two weeks. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 1, 3, 10 and 20 mg/kg, starting from 1 mg/kg.


Treatment: Drugs: HLX20
a Human Monoclonal Antibody Targeting Programmed Death Ligand-1 (PD-L1) Protein

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose of HLX20 in solid tumors patients - The target toxicity rate in this study for the MTD is set at 0.3 ( 30% DLT) identified by an adaptive Bayesian dose-finding design .
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Maximum serum concentration (Cmax) of HLX20.
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Minimum serum concentration (Cmin) of HLX20.
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Area under serum concentration-time curve within one dosing interval (AUC0-tau) of HLX20.
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Terminal elimination half-life (T1/2) of HLX20 in different cohorts
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
Clearance rate (CL) of HLX20
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Volume of distribution at steady state (Vss) of HLX20.
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Immunogenicity - The presence and percentage of anti-HLX20 antibody
Timepoint [7] 0 0
1 year
Secondary outcome [8] 0 0
Disease control rate (DCR) - Number of patients with complete response/partial response/stable disease divided by the total number of patients treated
Timepoint [8] 0 0
1 year
Secondary outcome [9] 0 0
Overall response rate (ORR). - Number of patients with confirmed complete or partial response, divided by the total number of treated patients with measurable disease at baseline
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
Receptor occupancy of PD-L1 on human T-cells.
Timepoint [10] 0 0
1 year

Eligibility
Key inclusion criteria
1. Males or females of 18 years of age or older (or per local regulations).

2. Have histologically-proven measurable, or evaluable advanced (systemically or locally
progressive), or metastatic solid tumors 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Kinghorn cancer centre - Darlinghurst
Recruitment hospital [2] 0 0
Macquarie University - Darlinghurst
Recruitment hospital [3] 0 0
Sunshine Coast University Hospital - Brisbane
Recruitment hospital [4] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [5] 0 0
CMAX Clinical research - Adelaide
Recruitment hospital [6] 0 0
Cabrini Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2109 - Darlinghurst
Recruitment postcode(s) [3] 0 0
4000 - Brisbane
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3144 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shanghai Henlius Biotech
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, dose escalation, first-in-human study of HLX20, an anti-PD-L1
monoclonal antibody, in patients with metastatic or recurrent solid tumors who have failed
standard therapy.
Trial website
https://clinicaltrials.gov/show/NCT03588650
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rosita Hsieh, MD
Address 0 0
Country 0 0
Phone 0 0
+886-2-27927927
Fax 0 0
Email 0 0
rhsieh@henlix.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03588650