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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04450901




Registration number
NCT04450901
Ethics application status
Date submitted
8/06/2020
Date registered
30/06/2020
Date last updated
30/06/2020

Titles & IDs
Public title
Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors
Scientific title
A Phase 1, Open-Label, Multicenter, Single Arm, Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
YBL006C101
Universal Trial Number (UTN)
Trial acronym
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 - YBL-006
Treatment: Drugs - YBL-006
Treatment: Drugs - YBL-006
Treatment: Drugs - YBL-006

Experimental: Cohort A1 group - YBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg

Experimental: Cohort A2 group - YBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg

Experimental: Cohort A3 group - YBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg

Experimental: Cohort A4 group - YBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg


Treatment: Drugs: YBL-006
Route of Administration: IV infusion; 0.5 mg/kg Q2W

Treatment: Drugs: YBL-006
Route of Administration: IV infusion; 2 mg/kg Q2W

Treatment: Drugs: YBL-006
Route of Administration: IV infusion; 5 mg/kg Q2W

Treatment: Drugs: YBL-006
Route of Administration: IV infusion; 10 mg/kg Q2W

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

Outcomes
Primary outcome [1] 0 0
Safety and tolerability measure through Adverse Events/Serious Adverse Events - Treatment-related adverse events as assessed by CTCAE v5.0 or higher
Timepoint [1] 0 0
Measurements at Baseline till Follow up from 90 days of last dose
Primary outcome [2] 0 0
Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure - Measured by result of the Vital Sign- blood pressure
Timepoint [2] 0 0
Measurements at Baseline till Follow up from 90 days of last dose
Primary outcome [3] 0 0
Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate - Measured by result of the Vital Sign- heart rate
Timepoint [3] 0 0
Measurements at Baseline till Follow up from 90 days of last dose
Primary outcome [4] 0 0
Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG - Measured by result of the ECG QT Interval
Timepoint [4] 0 0
Measurements at Baseline till Follow up from 90 days of last dose
Primary outcome [5] 0 0
Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam - Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.
Timepoint [5] 0 0
Measurements at Baseline till Follow up from 90 days of last dose
Primary outcome [6] 0 0
To establish the recommended Phase 2 dose (RP2D) of YBL-006 in patients with advanced solid tumors - Measured through increase in anti-drug antibody (ADA) levels
Timepoint [6] 0 0
Measurements at Baseline
Secondary outcome [1] 0 0
pharmacokinetic (PK) profile of YBL-006 - PK is assessed by parameter- area under the curve (AUC)
Timepoint [1] 0 0
Measured at C1D1 till Follow up from 90 days of last dose
Secondary outcome [2] 0 0
pharmacokinetic (PK) profile of YBL-006 - PK is assessed by parameter- maximum (or peak) serum concentration (Cmax)
Timepoint [2] 0 0
Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose
Secondary outcome [3] 0 0
pharmacokinetic (PK) profile of YBL-006 - PK is assessed by parameter- time of peak concentration (Tmax)
Timepoint [3] 0 0
Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose

Eligibility
Key inclusion criteria
1. Written consent on an institutional review board (IRB)/independent ethics committee
(IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.

2. Male or female aged =18 years at the time of ICF

3. Life expectancy of at least 3 months

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

5. Availability of archival tumor tissue and consent to provide archival tumor for
retrospective biomarker analysis, or consent to undergo a fresh tumor biopsy during
screening

6. For patients in dose escalation only: Histologically confirmed solid tumors [except
primary central nervous system (CNS) tumors] that is unresectable, locally advanced,
or metastatic and has progressed following all standard treatments or is not
appropriate for standard treatments

7. Must have at least one measurable lesion based on response evaluation criteria in
solid tumors (RECIST) Version 1.1. A previously irradiated lesion can be considered a
target lesion if the lesion is well defined, measurable and there is objective
evidence of interval increase in size.

8. Central nervous system (CNS) metastasis must be without evidence of progressive
neurological symptoms or requires increasing doses of corticosteroids to control the
CNS disease for at least 4 weeks. If a patient requires corticosteroids for management
of CNS disease, the dose must have been stable with low-dose (same or less than 10
mg/day prednisone or equivalent) for at least two weeks preceding C1D1;

9. Immunosuppressive doses of systemic medications, such as steroids (doses > 10 mg/day
prednisone or equivalent) must be discontinued at least 2 weeks before IP
administration;

10. Prior surgery that required general anesthesia must be completed at least 14 days
before IP administration. Surgery requiring local/epidural anesthesia must be
completed at least 72 hours before IP administration and patients should be recovered;

11. Adequate hematological and biological function, confirmed by the following laboratory
values:

Neutrophils = 1000/µL Platelets = 75,000/µL Hemoglobin = 9.0 g/dL (may have been
transfused) Creatinine = 1.5×upper limit of normal (ULN) Aspartate aminotransferase
(AST) = 2.5×ULN (Except with liver metastasis, AST = 5×ULN) Alanine aminotransferase
(ALT) = 2.5×ULN (Except with liver metastasis, AST = 5×ULN) Bilirubin = 1.5×ULN
(except patients with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL)

12. Women must meet one of the following criteria: postmenopausal for at least 24
consecutive months; surgically incapable of bearing children (i.e., have had a
hysterectomy or bilateral oophorectomy); or utilizing a reliable form of
contraception. In general, the decision for appropriate methods to prevent pregnancy
should be determined via discussions between the Investigator and the study patient.
Women of childbearing potential (WOCBP) must agree to use a reliable form of
contraceptive during the study Treatment Period and for at least 120 days following
the last dose of IP.

13. Men must agree to the use of acceptable contraceptive use and avoid sperm donation,
during the study Treatment Period and for at least 180 days after the last dose of IP.

14. For Expansion Cohort, patients enrolling must also meet the following inclusion
criteria:

Confirmed diagnosis of one of the following:

1. Histologically or cytologically confirmed diagnosis of stage IV NSCLC with high (>
50%) PD-L1 tumor expression as determined by immunohistochemistry (IHC) without
epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or
anaplastic lymphoma kinase (ALK) translocation;

2. Histologically confirmed diagnosis of unresectable stage III or metastatic MEL
(excluding uveal or ocular melanoma), not amenable to local therapy

3. Unresectable or metastatic, MSI-H or dMMR, locally confirmed by polymerase chain
reaction (PCR)

- Solid tumors that have progressed following prior treatment or who have no
satisfactory alternative treatment options or

- Colorectal cancer (CRC) that has progressed following treatment with at least one
line of therapy

4. Histologically or cytologically confirmed recurrent or metastatic HNSCC that has
progressed following platinum-based treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of severe hypersensitivity reactions to other monoclonal antibodies;

2. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic
T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or
drug specifically targeting T-cell co-stimulation or immune checkpoint pathways;

3. Chemotherapy, radiation therapy, biological cancer therapy, or tyrosine kinase
inhibitor (TKI) therapy within 2 weeks or 5 half-lives (whichever is the longer)prior
to the first dose of IP, or who has not recovered to National Cancer Institute (NCI)-
Common Terminology Criteria for Adverse Events (CTCAE) version 5 or higher Grade 1 or
better from the AEs due to cancer therapeutics administered more than 2 weeks earlier;
(palliative radiation treatment with a limited field of radiation is allowed up to 14
days prior to first dose of YBL-006)

4. Prior malignancy active within the previous 2 years except for 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, or localized
prostate cancer;

5. Active infection (viral, bacterial, or fungal) requiring IV antimicrobial treatment
within 14 days before the first dose of YBL-006;

6. Has known chronic Hepatitis B (e.g., HBsAg reactive) without sufficient anti-viral
treatment (prior treatment duration should be more than 3 months), Hepatitis C
infection, or human immunodeficiency virus (HIV);

7. Has active or history of interstitial lung disease (ILD), or has had a history of
pneumonitis that has required oral or IV steroids;

8. Evidence of bleeding diathesis;

9. Any active or suspected autoimmune disease or a documented history of autoimmune
disease, or history of a syndrome that required systemic steroids or immunosuppressive
medications, except for patients with vitiligo or resolved childhood asthma/atopy;

10. Receipt of live, attenuated vaccine within 28 days prior to the first dose of IP
(Note: Patients, if enrolled, should not receive live vaccine during the study and 180
days after the last dose of IP). Vaccination with a killed vaccine is permitted at any
time with consultation with the Medical Monitor;

11. Known current drug or alcohol abuse;

12. Apparent active or latent tuberculosis infection (purified protein derivative [PPD]
test is not required) as indicated by any of the following: PPD recently converted to
positive; chest x-ray with definitive evidence of active infectious infiltrate;

13. Presence of any other condition that may increase the risk associated with study
participation or may interfere with the interpretation of study results, and, in the
opinion of the Investigator, would make the patient inappropriate for entry into the
study.; Concurrent medical condition requiring the use of immunosuppressive
medications or immunosuppressive doses of systemic corticosteroids (doses 10 mg/day
prednisone or equivalent);

14. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be
continued if the patient is on a stable dose. Non-absorbed intra-articular steroid
injections will be permitted;

15. Use of other investigational therapy within 28 days before IP administration;

16. Non-study related minor surgical procedure (e.g. placement of a central venous access
port) = 5 days, or major surgical procedure = 21 days, prior to first dose of IP; in
all cases, the patient must be sufficiently recovered and stable before treatment
administration.

17. Psychiatric illness or social situation that would preclude study compliance;

18. Patient has clinically significant, uncontrolled, cardiovascular disease including
congestive heart failure Grade III or IV according to the New York Heart Association
(NYHA) classification; myocardial infarction or unstable angina within the previous 6
months, uncontrolled hypertension, or clinically significant, uncontrolled
arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., Type II
second degree heart block or third degree heart block);

19. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 470 msec.
Patient has a history of prolonged QT syndrome or Torsades de pointes. Patient has a
familial history of prolonged QT syndrome.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet 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
Recruitment hospital [1] 0 0
Macquarie University - Macquarie
Recruitment postcode(s) [1] 0 0
2109 - Macquarie
Recruitment outside Australia
Country [1] 0 0
Korea, Republic of
State/province [1] 0 0
Gyeonggi-do
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Y Biologics Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, open-label, multicenter, dose-escalation/dose-expansion study of YBL-006.
This multicenter study will be conducted in approximately 18-24 patients in the dose
escalation phase, and up to more than 80 patients in dose expansion phase.
Trial website
https://clinicaltrials.gov/show/NCT04450901
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Myungsuk Kim
Address 0 0
Y-Biologics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Myungsuk Kim
Address 0 0
Country 0 0
Phone 0 0
-2-558-5383
Fax 0 0
Email 0 0
mskim@ybiologics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04450901