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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04097769




Registration number
NCT04097769
Ethics application status
Date submitted
28/08/2019
Date registered
20/09/2019
Date last updated
12/12/2022

Titles & IDs
Public title
The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
Scientific title
A Phase I, First-in-Human Study Evaluating the Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
Secondary ID [1] 0 0
HX009-I-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HX009

Other: HX009 - Study treatment: HX009 administered every 2 weeks (14 \[±1\] days) via intravenous infusion.


Treatment: Drugs: HX009
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Adverse Events (AEs)
Timepoint [1] 0 0
All AEs up to 90 days after the last dose of study drug
Primary outcome [2] 0 0
Number of Participants With Dose-Limiting Toxicities (DLT) of HX009
Timepoint [2] 0 0
At the end of Cycle2(each cycle is 14 days)
Secondary outcome [1] 0 0
Time for Cmax (Tmax) of HX009
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [2] 0 0
Terminal Half-life (t½)of HX009
Timepoint [2] 0 0
Approximately 2 years
Secondary outcome [3] 0 0
Area Under the Serum Concentration-time Curve (AUC)
Timepoint [3] 0 0
Approximately 2 years
Secondary outcome [4] 0 0
Number of Participants With Positive Anti-Drug Antibody (ADA) of HX009
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Objective response rate(ORR) Per Investigator Assessment Using RECIST 1.1
Timepoint [5] 0 0
Approximately 2 years

Eligibility
Key inclusion criteria
1. Male or female subject aged 18 to 70 years, inclusive.
2. Eastern Cooperative Oncology Group performance status of 0 to 1.
3. 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.
4. At least 1 measurable tumor according to RECIST v1.1 (see Appendix 7 of the protocol).
5. Life expectancy =12 weeks.
6. 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).
7. 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).
8. 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.
9. Voluntarily agrees to participate by giving written informed consent and is willing and able to comply with protocol and scheduled visits.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. 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.
3. Allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components.
4. 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.
5. 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).
6. Radiation therapy (localized radiation therapy for therapeutic purpose is allowed) within 4 weeks of the first dose of study treatment.
7. Female subject who is pregnant or lactating.
8. Tests positive for human immunodeficiency virus, or has active hepatitis B virus or hepatitis C virus.
9. 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.
10. Planning major surgery during the study including the screening period.
11. 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.
12. Active peptic ulcer, incomplete intestinal obstruction, active gastrointestinal bleeding, and perforation.
13. Lung disease, interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease, interstitial pneumonia, etc.
14. Uncontrolled stable systemic diseases such as cardiovascular and cerebrovascular diseases, diabetes, high blood pressure, etc.
15. History of infection with human immunodeficiency virus, or other acquired, congenital immunodeficiency disease, or history of organ transplantation, or history of stem cell transplantation.
16. Current, or history of, tuberculosis or evidence of latent tuberculosis infection: positive QuantiFERON-TB Gold assessment at screening.
17. 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.
18. Cancerous meningitis.
19. Has received hematopoietic stimulating factors such as colony stimulating factor and erythropoietin within 2 weeks before the first dose of study treatment.
20. Use of any live vaccines within 4 weeks before the first dose of study treatment.
21. Any major surgery within 4 weeks before the first dose of study treatment (except for diagnostic surgery).
22. A history of psychotropic substance abuse who is unable to quit or who has a history of mental disorders.
23. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/09/2022
Sample size
Target
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St George Private Hospital - Kogarah
Recruitment postcode(s) [1] 0 0
2217 - Kogarah

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Waterstone Hanxbio Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/study/NCT04097769
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul de Souza
Address 0 0
St George Private Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04097769