Advanced Solid TumorsPhase 1HLX20NCT03588650
A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting PD-L1Protein in Patients With Advanced Solid Tumors
A Phase 1 study testing HLX20 in people with Advanced Solid Tumors, run by Shanghai Henlius Biotech at 6 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- HLX20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 6 sitesAustralia
- Study dates
- 7 Aug 2018to 28 Jun 2021
- 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
- Males or females of 18 years of age or older (or per local regulations).
- 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).
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
- Able to comprehend and provide informed consent.
- A life expectancy longer than 3 months in the opinion of the Investigator.
- Adequate hematologic functions, as defined by: absolute neutrophil counts
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- ≥ 1500/mm3; a hemoglobin level ≥ 10 g/dL; a platelet count ≥ 100,000/mm3.
- 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.
- Adequate renal function, as defined by the creatinine clearance ≥ 50 mL/minute (as calculated by the Cockcroft-Gault formula).
- 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.
- 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).
- 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.
- 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.
- Child-Pugh score of A (patients with hepatocellular carcinoma only).
- Able to be followed up as required by the study protocol.
Who cannot join
- 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.
- 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;
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- 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.
- 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).
- Females who are pregnant, lactating, or intend to become pregnant during their participation in this study.
- Known history of human immunodeficiency virus infection.
- 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.
- 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).
- History of primary immunodeficiency or allogeneic transplantation.
- 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.
- History of interstitial lung disease.
- 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.
- 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, is not in the best interest of the patient to participate.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Australia6 sites
CMAX Clinical research
Adelaide, South Australia, 5000
Sunshine Coast University Hospital
Brisbane, Queensland, 4000
Kinghorn cancer centre
Darlinghurst, New South Wales, 2010
Macquarie University
Darlinghurst, New South Wales, 2109
Cabrini Hospital
Melbourne, Victoria, 3144
Gold Coast Hospital
Southport, Queensland, 4215
About this study
Official 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
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.
Read the detailed description
Tumor microenvironment plays an important role in the interaction of immune cells with cancer . The identification of programmed cell death receptor 1 (PD-1) and programmed death ligand-1 (PD-L1) have provided the scientific rationale and supports the clinical development of agents targeting this pathway. Currently, PD-1 and PD-L1 inhibitory pathway blockade has demonstrated impressive activity against a spectrum of multiple tumor types, including Hodgkin's lymphoma, melanoma, bladder cancer, lung cancer, renal cell carcinoma.
HLX20 is a novel anti-PD-L1 monoclonal antibody. In the nonclinical pharmacology studies, HLX20 has demonstrated anti-tumor activities in xenogenic animal models comparable to currently available anti-PD-L1 monoclonal antibodies. HLX20 binds to PD-1 and PD-L1 inhibitory pathway and human PD-L1 at high affinity, and mouse PD-L1 at much lower affinity. HLX20 does not cause hemolysis to human red blood cells and has no local irritation to human tissues. (The results of pharmacokinetic (PK)/toxicokinetic studies in cynomolgus studies have been described in detail in the Investigator's Brochure.)The no-observable adverse effect level (NOAEL) is set at 100 mg/kg every 2 weeks for 13 weeks in cynomolgus studies.
Based on these results, the initial dose 1 mg/kg every 2 weeks was chosen for this study .This dose level is approximately 30-fold lower than the human equivalent dose of NOAEL from preclinical toxicology studies. An adaptive Bayesian dose-finding design will be used to identify the MTD (maximum tolerated dose). The target toxicity rate for the MTD is set at 0.3 and the maximum sample size is 30.The safety profiles at different dose levels, PK parameters, biomarkers, pharmacodynamic markers, immunogenicity as well as the preliminary efficacy of the drug, will also be investigated in this study.
- Conditions
- Advanced Solid Tumors
- Being tested
- HLX20
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLX20Drug
a Human Monoclonal Antibody Targeting Programmed Death Ligand-1 (PD-L1) Protein
| Study group | Role | What they receive |
|---|---|---|
| HLX20, in patients with solid tumors | Experimental | 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. Receives: Drug: HLX20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: 1 year
Secondary outcomes (10)
Maximum serum concentration (Cmax) of HLX20.
Measured: 1 year
Minimum serum concentration (Cmin) of HLX20.
Measured: 1 year
Area under serum concentration-time curve within one dosing interval (AUC0-tau) of HLX20.
Measured: 1 year
Terminal elimination half-life (T1/2) of HLX20 in different cohorts
Measured: 1 year
Clearance rate (CL) of HLX20
Measured: 1 year
Volume of distribution at steady state (Vss) of HLX20.
Measured: 1 year
Immunogenicity
The presence and percentage of anti-HLX20 antibody
Measured: 1 year
Disease control rate (DCR)
Number of patients with complete response/partial response/stable disease divided by the total number of patients treated
Measured: 1 year
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
Measured: 1 year
Receptor occupancy of PD-L1 on human T-cells.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start7 Aug 2018
- Primary completion28 Jun 2021
- Study completion28 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Shanghai Henlius BiotechThe sponsor's other registered studies.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Henlius Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588650
- Sponsor's protocol ID
- HLX20-001
- Acronym
- HLX20
- Status last verified
- Jun 2022
- First submitted
- 22 Jun 2018
- Last updated
- 3 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03588650
- Acronym / sponsor ID
- HLX20 / HLX20-001
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Shanghai Henlius BiotechIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2018 (actual)
- Primary completion
- 28 Jun 2021 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 17 Jul 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.
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.
Detailed description
Tumor microenvironment plays an important role in the interaction of immune cells with cancer . The identification of programmed cell death receptor 1 (PD-1) and programmed death ligand-1 (PD-L1) have provided the scientific rationale and supports the clinical development of agents targeting this pathway. Currently, PD-1 and PD-L1 inhibitory pathway blockade has demonstrated impressive activity against a spectrum of multiple tumor types, including Hodgkin's lymphoma, melanoma, bladder cancer, lung cancer, renal cell carcinoma.
HLX20 is a novel anti-PD-L1 monoclonal antibody. In the nonclinical pharmacology studies, HLX20 has demonstrated anti-tumor activities in xenogenic animal models comparable to currently available anti-PD-L1 monoclonal antibodies. HLX20 binds to PD-1 and PD-L1 inhibitory pathway and human PD-L1 at high affinity, and mouse PD-L1 at much lower affinity. HLX20 does not cause hemolysis to human red blood cells and has no local irritation to human tissues. (The results of pharmacokinetic (PK)/toxicokinetic studies in cynomolgus studies have been described in detail in the Investigator's Brochure.)The no-observable adverse effect level (NOAEL) is set at 100 mg/kg every 2 weeks for 13 weeks in cynomolgus studies.
Based on these results, the initial dose 1 mg/kg every 2 weeks was chosen for this study .This dose level is approximately 30-fold lower than the human equivalent dose of NOAEL from preclinical toxicology studies. An adaptive Bayesian dose-finding design will be used to identify the MTD (maximum tolerated dose). The target toxicity rate for the MTD is set at 0.3 and the maximum sample size is 30.The safety profiles at different dose levels, PK parameters, biomarkers, pharmacodynamic markers, immunogenicity as well as the preliminary efficacy of the drug, will also be investigated in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HLX20, in patients with solid tumors | Experimental | Drug: HLX20Each 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Males or females of 18 years of age or older (or per local regulations).
- 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).
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
- Able to comprehend and provide informed consent.
- A life expectancy longer than 3 months in the opinion of the Investigator.
Key exclusion criteria (23 listed)
- 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.
- Concurrent unstable or uncontrolled medical conditions, including:
- 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).
- Females who are pregnant, lactating, or intend to become pregnant during their participation in this study.
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 |
|---|---|---|
| HLX20a Human Monoclonal Antibody Targeting Programmed Death Ligand-1 (PD-L1) Protein | Drug | HLX20, in patients with solid tumors |
Primary outcome
Maximum tolerated dose of HLX20 in solid tumors patients
Time frame: 1 year
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 .
10 secondary outcomes
Maximum serum concentration (Cmax) of HLX20.
Time frame: 1 year
Minimum serum concentration (Cmin) of HLX20.
Time frame: 1 year
Area under serum concentration-time curve within one dosing interval (AUC0-tau) of HLX20.
Time frame: 1 year
Terminal elimination half-life (T1/2) of HLX20 in different cohorts
Time frame: 1 year
Clearance rate (CL) of HLX20
Time frame: 1 year
Volume of distribution at steady state (Vss) of HLX20.
Time frame: 1 year
Immunogenicity
Time frame: 1 year
Disease control rate (DCR)
Time frame: 1 year
Overall response rate (ORR).
Time frame: 1 year
Receptor occupancy of PD-L1 on human T-cells.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HLX20 in people with Advanced Solid Tumors, run by Shanghai Henlius Biotech at 6 sites in Australia.
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 15 inclusion and 23 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: finished, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Australia. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of HLX20 in solid tumors patients (time frame: 1 year). 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 3 Jun 2022; AzTrials last refreshed its copy on 7 Nov 2026.