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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04674683




Registration number
NCT04674683
Ethics application status
Date submitted
7/12/2020
Date registered
19/12/2020
Date last updated
27/07/2023

Titles & IDs
Public title
Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Nivolumab in Patients With Advanced Melanoma
Scientific title
A Multicenter, Randomized, Double-Blind Phase 3 Study of HBI-8000 Combined With Nivolumab Versus Placebo With Nivolumab in Patients With Unresectable or Metastatic Melanoma Not Previously Treated With PD-1 or PD-L1 Inhibitors
Secondary ID [1] 0 0
HBI-8000-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Melanoma 0 0
Progressive Brain Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HBI-8000 in combination with nivolumab
Treatment: Drugs - Placebo in combination with nivolumab

Experimental: Test Arm - HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Placebo Comparator: Control Arm - Placebo oral BIW + nivolumab IV at specific doses on specific days


Treatment: Drugs: HBI-8000 in combination with nivolumab
Patients will take 30 mg of HBI-8000 orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV will be administered by intravenous infusion at specific doses on specific days in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice. In adolescent patients with body weight < 40 kg, nivolumab will be dosed at specific doses on specific days.

Treatment: Drugs: Placebo in combination with nivolumab
Patients will take 30 mg of Placebo orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV at specific doses will be administered by intravenous infusion in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Outcome
Timepoint [1] 0 0
From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
Primary outcome [2] 0 0
Primary Outcome
Timepoint [2] 0 0
From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months
Secondary outcome [1] 0 0
Secondary Outcome
Timepoint [1] 0 0
From date of randomization to death due to any cause, assessed up to 48 months
Secondary outcome [2] 0 0
Secondary Outcome
Timepoint [2] 0 0
From date of randomization until the end of study, assessed up to 48 months

Eligibility
Key inclusion criteria
1. Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or
Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).

2. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before
randomization.

3. Tumor tissue available for PD-L1 testing at central lab. PD-L1 expression level is
required for randomization. In order to be randomized, a patient must be classified as
PD-L1 positive or PD-L1 negative according to the following criteria:

- PD-L1 positive (= 1% tumor cell membrane staining in a minimum of a hundred
evaluable tumor cells) vs

- PD-L1 negative (< 1% tumor cell membrane staining in a minimum of a hundred
evaluable tumor cells).

Note: If an insufficient amount of tumor tissue from an unresectable or metastatic
site is available prior to the start of the Screening Phase, patients must consent to
allow the acquisition of additional tumor tissue for assessment of the biomarker.

4. Males or females 12 years of age or older.

5. ECOG performance status =1 for age =18 years, Lansky performance score =80% for age 12
to 17 years.

6. At least one measurable lesion defined by RECIST 1.1 criteria, (separate from the
lesion to be used for tumor tissue collection for PD-L1 testing) not counting brain
metastasis with:

- Longest diameter =10 mm by CT (when slice thickness is =5 mm); or = 2× slice
thickness (when slice thickness is >5 mm)

- Pathologically enlarged lymph node: =15 mm in short axis by CT (when slice
thickness is =5 mm)

- Clinical: =10 mm (that can be accurately measured with calipers).

7. Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or
metastatic melanoma, except for the following, provided that the patient has recovered
from all treatment-related toxicities:

- BRAF mutation targeting therapy > 4 weeks before administration of Study
Treatment.

- Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors or anti-CTLA-4) is
allowed if disease progression/or recurrence occurred at least 6 months after the
last dose and no clinically significant immune related toxicities leading to
treatment discontinuation were observed

- Adjuvant interferon therapy must have been completed > 6 weeks before
administration of Study Treatment

8. Any prior radiotherapy or minor surgery must be completed at least 2 weeks and 1 week
respectively before Day 1 dosing and recovered from all treatment related toxicities

9. Screening laboratory results within 14 days prior to randomization:

- Hematology: WBC =3000/µL, neutrophils =1500/µL, platelets =100 × 103/µL,
hemoglobin =10.0 g/dL independent of transfusion. The use of erythropoietic
growth factor to achieve hemoglobin (Hgb) = 10 g/dl is acceptable.

- The CrCL= 30 mL/min using Cockcroft-Gault formula.

- AST and ALT =3 × ULN, alkaline phosphatase =2.5 × ULN unless bone metastases
present (patients with documented bone metastases: alkaline phosphatase <5 x
ULN), bilirubin = 1.5 × ULN (unless known Gilbert's disease where it must be = 3
× ULN), serum albumin = 3.0 g/dL).

10. Negative serum pregnancy test at baseline for women of childbearing potential.

11. Females of childbearing potential (non-surgically sterile or premenopausal female
capable of becoming pregnant) and all males (due to potential risk of drug exposure
through the ejaculate) must agree to use adequate birth control measures from study
start, during the study and for 5 months after the last dose of Study Drug. Acceptable
methods of birth control in this trial include two highly effective methods of birth
control (as determined by the Investigator; one of the methods must be a barrier
technique) or abstinence.

12. Have the ability to understand and the willingness to sign a written informed consent
document, comply with study scheduled treatment, visits and assessments.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of = Grade 3 hypersensitivity reactions to monoclonal antibodies.

2. Previous treatment with a PD-1, PD-L1, PD-L2, CTLA-4 inhibitor, or any other agents
targeting T-cell co-stimulation or immune checkpoint pathways for unresectable or
metastatic melanoma.

3. History of a cardiovascular illness including: congestive heart failure (New York
Heart Association Grade III or IV); unstable angina or myocardial infarction within
the previous 6 months; or symptomatic cardiac arrhythmia despite medical management.
QT interval corrected by heart rate using QTcF >450 ms in males or >470 ms in females,
or congenital long QT syndrome.

4. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood
pressure (DBP) >100 mmHg.

5. Patients with new, active, or progressive brain metastases or leptomeningeal disease
with except when considered for a separate special open-label cohort described in
protocol Section 5.3 or "Inclusion of Patients with Progressive Brain Metastasis"
section in the protocol synopsis.

6. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled
peptic ulcer, or bowel resection that affects absorption of orally administered drugs.

7. Active, known, or suspected autoimmune disease, except for Type I diabetes mellitus,
hypothyroidism requiring only hormone replacement, or skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic therapy.

8. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.

9. Known history of testing positive for HIV, known AIDS.

10. Hepatitis B surface antigen positive or hepatitis C antibody positive. Further
investigation per institutional practices may be performed to exclude active
infection.

11. Patients with a condition requiring chronic systemic treatment with either
corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive
medications within 14 days before administration of Study Treatment. Inhaled or
topical steroids, or adrenal replacement dose of corticosteroids at dose = 10 mg/day
prednisone equivalent are permitted.

12. Use of another investigational agent (drug or vaccine not marketed for any indication)
28 days or before administration of Study Treatment. If the investigational agent is a
monoclonal antibody then within 3 months before administration of Study Treatment

13. Pregnant or breast-feeding women.

14. Second malignancy unless in remission for 2 years or locally curable cancers that have
been treated with curative intent with no evidence of recurrence, such as:

- Basal or squamous cell skin cancer

- Superficial bladder cancer

- Carcinoma in situ of cervix or breast

- Incidental prostate cancer

- Non melanomatous skin cancer

- Carcinoma in situ of the cervix treated with curative intent

- Prostate cancer treated with curative intent with serum prostate specific antigen
(PSA) < 2.0 ng/mL

15. Patients with medical conditions requiring administration of strong cytochrome P450
(CYP), CYP3A4 Inducers and Inhibitors.

16. Uncontrolled adrenal insufficiency or active chronic liver disease.

17. Has received approved live vaccine/live attenuated vaccines within 30 days of planned
Cycle 1 Day 1. Inactivated viral vaccines or vaccines based upon subviral component
are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed.
COVID-19 vaccination should be administered at least 7 days before Cycle 1 Day 1.

18. Underlying medical conditions that, in the Investigator's opinion, will make the
administration of Study Treatment hazardous or obscure the interpretation of toxicity
determination or AEs.

19. Unwilling or unable to comply with procedures required in this protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
12/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
480
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [2] 0 0
University of the Sunshine Coast - Buderim
Recruitment hospital [3] 0 0
University of the Sunshine - Sippy Downs
Recruitment hospital [4] 0 0
Icon Cancer Centre Wesley - South Brisbane
Recruitment hospital [5] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [6] 0 0
Goulburn Valley Health - Shepparton
Recruitment hospital [7] 0 0
Royal Brisband and Women's Hospital - Brisbane
Recruitment hospital [8] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [9] 0 0
Affinity Clinical Research - Nedlands
Recruitment hospital [10] 0 0
Tweed Hospital - Tweed Heads
Recruitment hospital [11] 0 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 0 0
- Wahroonga
Recruitment postcode(s) [2] 0 0
4556 - Buderim
Recruitment postcode(s) [3] 0 0
4556 - Sippy Downs
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment postcode(s) [5] 0 0
- Ballarat
Recruitment postcode(s) [6] 0 0
- Shepparton
Recruitment postcode(s) [7] 0 0
- Brisbane
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- Liverpool
Recruitment postcode(s) [9] 0 0
- Nedlands
Recruitment postcode(s) [10] 0 0
- Tweed Heads
Recruitment postcode(s) [11] 0 0
- Waratah
Recruitment outside Australia
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United States of America
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California
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Florida
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Indiana
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United States of America
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Kentucky
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Maryland
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Missouri
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Montana
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North Carolina
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Ohio
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Utah
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Wisconsin
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Graz
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Innsbruck
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Brasschaat
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Ghent
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Liège
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Napoli
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Palermo
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Roma
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Siena
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Verona
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Nagano
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Osaka
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Sunto-gun
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Tokho
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Fukuoka
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Japan
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Niigata
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Japan
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Okayama
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Korea, Republic of
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Gyeonggi-do
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Gyeonggi
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Jeollanam-do
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Jung-gu
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Seoul
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New Zealand
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Auckland
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New Zealand
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Hamilton
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Tauranga
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Puerto Rico
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Rio Piedras
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Singapore
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Singapore
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South Africa
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Gauteng
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South Africa
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Western Cape
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Spain
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Barcelona
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Madrid
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Málaga
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Spain
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Sevilla
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Spain
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Zaragoza
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United Kingdom
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Hampshire
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United Kingdom
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Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
HUYABIO International, LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 3 study to compare the efficacy and safety of HBI-8000 or Placebo combined
with nivolumab on patients with unresectable or metastatic melanoma and eligible patients who
are not adolescents or patients with new, progressive brain metastasis will be stratified by
PD-L1 expression and LDH level.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04674683
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John T Ning, MD, PhD
Address 0 0
HUYABIO International, LLC.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
M Tawashi
Address 0 0
Country 0 0
Phone 0 0
1-858-209-1695
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04674683