Advanced Solid TumorPhase 1NCT04097769
The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
A Phase 1 study testing HX009 in people with Advanced Solid Tumor, run by Waterstone Hanxbio Pty Ltd at 1 site in Australia.
Trial summary
This is a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- HX009
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteAustralia
- Study dates
- 12 Jun 2019to 29 Sep 2022
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject aged 18 to 70 years, inclusive.
- Eastern Cooperative Oncology Group performance status of 0 to 1.
- Histologically confirmed advanced malignant tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
- At least 1 measurable tumor according to RECIST v1.1 (see Appendix 7 of the protocol).
- Life expectancy ≥12 weeks.
- A subject with a history of brain/meninges metastases who has received prior topical treatment (surgery/radiotherapy) before the start of the study and is clinically stable for at least 3 months is allowed (prior treatment with corticosteroids is permitted; however, if a subject requires systemic concomitant treatment with corticosteroids, they must be excluded).
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- Adequate organ function, as indicated by the following laboratory values, within 14 days before signing informed consent:
- Hematology
- Hemoglobin ≥100 g/L (no blood transfusion is allowed within 14 days before signing informed consent)
- Absolute neutrophil count ≥1.5 × 109/L
- Platelet count ≥100 × 109/L Biochemistry
- Total bilirubin ≤1.5 × upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (ALT and AST ≤5 × ULN for subjects with liver metastases)
- Serum creatinine ≤1 × ULN
- Prothrombin time/international normalized ratio ≤1.5 × ULN or activated partial thromboplastin time ≤1.5 × ULN (for subjects on anticoagulants, prothrombin time or activated partial thromboplastin time must be within the normal range for anticoagulants).
- Male subject: must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 12 months after the last dose of the study treatment.
- Female subject: must not be pregnant; or must not be of childbearing potential as defined in in Appendix 5; or if of childbearing potential, must agree to use highly effective birth control methods during the study treatment period and for at least 12 months after the last dose of the study treatment.
- Voluntarily agrees to participate by giving written informed consent and is willing and able to comply with protocol and scheduled visits.
Who cannot join
- For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4):
- Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4, CD47, or any other immunotherapy or immune-oncology agent within 4 weeks of the first dose study treatment
- Subjects must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
- Any adverse events reported while receiving prior immunotherapy must have completely resolved or resolved to Grade 1 prior to screening for this study.
- Prior malignancy active within the previous 2 years except for the tumor for which a subject is enrolled in the study and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components.
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- Receipt of any immunotherapy, or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment; in the case of mAbs (for investigational use or immunotherapy), 6 weeks prior to the first dose of study treatment.
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy (except for subjects with metastatic prostate cancer on androgen deprivation treatment eg, goserelin, leuprorelin) for cancer. Concurrent use of hormones for noncancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. NOTE: Local treatment of isolated lesions for palliative intent is acceptable (eg, by local surgery or local radiotherapy).
- Radiation therapy (localized radiation therapy for therapeutic purpose is allowed) within 4 weeks of the first dose of study treatment.
- Female subject who is pregnant or lactating.
- Tests positive for human immunodeficiency virus, or has active hepatitis B virus or hepatitis C virus.
- Active, or history of, autoimmune disease (within the past 2 years) that may recur (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc) or are at high risk (eg, receiving an immunosuppressive treatment for an organ transplant); however, subjects with the following are allowed to enroll:
- Type I diabetes that is stable after a fixed dose of insulin
- Only requiring hormone replacement therapy for autoimmune hypothyroidism
- Skin disease that does not require treatment such as eczema, rash that accounts for <10% of the body surface, psoriasis without ophthalmic symptoms.
- Planning major surgery during the study including the screening period.
- Requiring systemic corticosteroids (dose equivalent to >10 mg prednisone/day) or other immunosuppressive drugs within 14 days before the first dose of study treatment or during the study. The following are allowed:
- Use of topical or inhaled glucocorticoids
- A brief course of corticosteroids (≤7 days) for prophylaxis or for treatment of non autoimmune conditions.
- Active peptic ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding, and perforation.
- Lung disease, interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease, interstitial pneumonia, etc.
- Uncontrolled stable systemic diseases such as cardiovascular and cerebrovascular diseases, diabetes, high blood pressure, etc.
- History of infection with human immunodeficiency virus, or other acquired, congenital immunodeficiency disease, or history of organ transplantation, or history of stem cell transplantation.
- Current, or history of, tuberculosis or evidence of latent tuberculosis infection: positive QuantiFERON-TB Gold assessment at screening.
- Severe infections within 4 weeks before the first dose of study treatment, or active infections within 2 weeks before the first dose that require oral or intravenous antibiotics.
- Cancerous meningitis.
- Has received hematopoietic stimulating factors such as colony stimulating factor and erythropoietin within 2 weeks before the first dose of study treatment.
- Use of any live vaccines within 4 weeks before the first dose of study treatment.
- Any major surgery within 4 weeks before the first dose of study treatment (except for diagnostic surgery).
- A history of psychotropic substance abuse who is unable to quit or who has a history of mental disorders.
- Other severe, acute or chronic medical or psychiatric diseases or laboratory abnormalities that, in the Investigator's opinion, may increase the study-related risks or interfere with the interpretation of the findings.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, First-in-Human Study Evaluating the Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
This is a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. The study will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and to evaluate the preliminary antitumor activity of HX009.
Read the detailed description
The study will follow a 3+3 dose-escalation scheme enrolling cohorts of at least 3 subjects sequentially at escalating doses. During study treatment, subjects will receive HX009 treatment via intravenous infusion once every 2 weeks. Dose escalation will continue until identification of an MTD or the maximum dose is reached. Dose-limiting toxicities (DLTs) will be assessed from the first dose of study treatment (Day 1) until 28 days later (Day 29).
The study is divided into a screening period (28 days before first dose), treatment period (up to 24 months), and survival follow-up period. Safety will be evaluated throughout the study up until 90 (±7) days after the last dose of study treatment. Blood samples will be collected at regular intervals for pharmacokinetics (PK) and immunogenicity evaluation. Tumor evaluation (assessed by the Investigator in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST 1.1] and immune RECIST [iRECIST]) to assess efficacy will start from the first dose and occur every 8 weeks in the first 12 months and every 12 weeks in the second 12 months and during the survival follow-up period.
- Conditions
- Advanced Solid Tumor
- Being tested
- HX009
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HX009Drug
Also called anti-PD-1/CD47 infusion protein
During study treatment, subjects will receive HX009 treatment via IV infusion once every 2 weeks at doses of 0.1, 0.3, 1, 2, 3, 5, and 7.5 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| HX009 | Other | Study treatment: HX009 administered every 2 weeks (14 [±1] days) via intravenous infusion. Receives: Drug: HX009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Measured: All AEs up to 90 days after the last dose of study drug
Number of Participants With Dose-Limiting Toxicities (DLT) of HX009
Severity of adverse events (AEs) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For the purpose of dose escalation, any of the following AEs occurring during the DLT observation period that were attributable to one or both study drugs were classified as DLTs.
Measured: At the end of Cycle2(each cycle is 14 days)
Secondary outcomes (5)
Time for Cmax (Tmax) of HX009
Time to reach HX009 maximum observed serum concentration.
Measured: Approximately 2 years
Terminal Half-life （t½）of HX009
HX009 terminal half-life.
Measured: Approximately 2 years
Area Under the Serum Concentration-time Curve (AUC)
HX009 area under the serum concentration-time curve .
Measured: Approximately 2 years
Number of Participants With Positive Anti-Drug Antibody (ADA) of HX009
ADA blood samples were assayed for anti-HX009 antibodies.
Measured: Cycles 1, 2, 3, 4, 5, 6, 7, 9, 13, and 17, and then every 8 cycles, Day 1: within 60 minutes before the start of the infusion(each cycle is 14 days)
Objective response rate(ORR) Per Investigator Assessment Using RECIST 1.1
The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start12 Jun 2019
- Primary completion18 Mar 2021
- Study completion29 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- 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
- Single group
- Model description
- HX009
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Waterstone Hanxbio Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul de Souza, Principal investigator, St George Private Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097769
- Sponsor's protocol ID
- HX009-I-01
- Status last verified
- Dec 2022
- First submitted
- 28 Aug 2019
- Last updated
- 12 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, First-in-Human Study Evaluating the Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT04097769
- Acronym / sponsor ID
- HX009-I-01
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Waterstone Hanxbio Pty LtdIndustry (pharma, biotech, devices)
- Study start
- 12 Jun 2019 (actual)
- Primary completion
- 18 Mar 2021 (actual)
- Study completion
- 29 Sep 2022 (actual)
- First posted
- 20 Sep 2019 (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 a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. The study will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and to evaluate the preliminary antitumor activity of HX009.
Detailed description
The study will follow a 3+3 dose-escalation scheme enrolling cohorts of at least 3 subjects sequentially at escalating doses. During study treatment, subjects will receive HX009 treatment via intravenous infusion once every 2 weeks. Dose escalation will continue until identification of an MTD or the maximum dose is reached. Dose-limiting toxicities (DLTs) will be assessed from the first dose of study treatment (Day 1) until 28 days later (Day 29).
The study is divided into a screening period (28 days before first dose), treatment period (up to 24 months), and survival follow-up period. Safety will be evaluated throughout the study up until 90 (±7) days after the last dose of study treatment. Blood samples will be collected at regular intervals for pharmacokinetics (PK) and immunogenicity evaluation. Tumor evaluation (assessed by the Investigator in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST 1.1] and immune RECIST [iRECIST]) to assess efficacy will start from the first dose and occur every 8 weeks in the first 12 months and every 12 weeks in the second 12 months and during the survival follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- HX009
| Arm | Type | Receives |
|---|---|---|
| HX009 | Other | Drug: HX009Study treatment: HX009 administered every 2 weeks (14 [±1] days) via intravenous infusion. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Male or female subject aged 18 to 70 years, inclusive.
- Eastern Cooperative Oncology Group performance status of 0 to 1.
- Histologically confirmed advanced malignant tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
- At least 1 measurable tumor according to RECIST v1.1 (see Appendix 7 of the protocol).
- Life expectancy ≥12 weeks.
Key exclusion criteria (31 listed)
- For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4):
- Prior malignancy active within the previous 2 years except for the tumor for which a subject is enrolled in the study and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components.
- Receipt of any immunotherapy, or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment; in the case of mAbs (for investigational use or immunotherapy), 6 weeks prior to the first dose of study treatment.
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy (except for subjects with metastatic prostate cancer on androgen deprivation treatment eg, goserelin, leuprorelin) for cancer. Concurrent use of hormones for noncancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. NOTE: Local treatment of isolated lesions for palliative intent is acceptable (eg, by local surgery or local radiotherapy).
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 |
|---|---|---|
| HX009Also: anti-PD-1/CD47 infusion proteinDuring study treatment, subjects will receive HX009 treatment via IV infusion once every 2 weeks at doses of 0.1, 0.3, 1, 2, 3, 5, and 7.5 mg/kg. | Drug | HX009 |
Primary outcome
Number of Participants Experiencing Adverse Events (AEs)
Time frame: All AEs up to 90 days after the last dose of study drug
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.
Number of Participants With Dose-Limiting Toxicities (DLT) of HX009
Time frame: At the end of Cycle2(each cycle is 14 days)
Severity of adverse events (AEs) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For the purpose of dose escalation, any of the following AEs occurring during the DLT observation period that were attributable to one or both study drugs were classified as DLTs.
5 secondary outcomes
Time for Cmax (Tmax) of HX009
Time frame: Approximately 2 years
Terminal Half-life （t½）of HX009
Time frame: Approximately 2 years
Area Under the Serum Concentration-time Curve (AUC)
Time frame: Approximately 2 years
Number of Participants With Positive Anti-Drug Antibody (ADA) of HX009
Time frame: Cycles 1, 2, 3, 4, 5, 6, 7, 9, 13, and 17, and then every 8 cycles, Day 1: within 60 minutes before the start of the infusion(each cycle is 14 days)
Objective response rate(ORR) Per Investigator Assessment Using RECIST 1.1
Time frame: Approximately 2 years
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 12 Dec 2022.
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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.
Paul de Souza principal investigator
St George Private Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HX009 in people with Advanced Solid Tumor, run by Waterstone Hanxbio Pty Ltd at 1 site 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 18 inclusion and 31 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 12 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Number of Participants Experiencing Adverse Events (AEs) (time frame: All AEs up to 90 days after the last dose of study drug). The study lists 2 primary outcomes in all. 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 12 Dec 2022.