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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/NCT04450901




Registration number
NCT04450901
Ethics application status
Date submitted
8/06/2020
Date registered
30/06/2020
Date last updated
5/12/2022

Titles & IDs
Public title
Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors
Scientific title
A Phase 1/2a, 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
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

Experimental: Cohort B1 - Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg

Experimental: Cohort B2 - Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 3 weeks (Q3W). Dose: 300 mg

Experimental: Cohort B2 reserve - Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments).
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 300 mg

Experimental: Cohort B3 - Tumor type: Metastatic NSCLC (Non-small-cell lung carcinoma), unresectable or metastatic, MSI-H (microsatellite instability-high) or dMMR (Deficient MisMatch Repair), recurrent or metastatic HNSCC (Head and neck squamous cell carcinoma), non-clear cell RCC (renal cell carcinoma), aSCC (anal squamous cell carcinoma), uterine cervical cancer, cSCC (cutaneous squamous cell carcinoma of the skin), uterine endometrial carcinoma, TMB-H (high tumor mutation burden) tumors, epithelial tumor of the penis (squamous cell carcinoma or adenocarcinoma), neuroendocrine tumor (any origin, pancreatic or non-pancreatic), and nasopharyngeal cancer.
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg


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

Treatment: Drugs: YBL-006
Route of administration : IV infusion, 200 mg Q2W

Treatment: Drugs: YBL-006
Route of administration : IV infusion, 300 mg Q3W

Treatment: Drugs: YBL-006
Route of administration : IV infusion, 300 mg Q2W

Treatment: Drugs: YBL-006
Route of administration : IV infusion, 200mg 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
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
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
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
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
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
Timepoint [6] 0 0
Measurements at Baseline
Secondary outcome [1] 0 0
pharmacokinetic (PK) profile of YBL-006
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
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
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 IRB/ IEC-approved ICF prior to any study-specific evaluation.

2. Male or female aged =18 years (or age of legal adult, whichever is older).

3. Life expectancy of at least 3 months.

4. ECOG performance status of 0 to 1.

5. Availability of archival tumour tissue and consent to provide archival tumour for
retrospective biomarker analysis, or consent to undergo a fresh tumour biopsy during
screening. Participants who do not have an existing (archived) tumour specimen and are
unwilling to undergo a biopsy may be enrolled with prior approval from the Sponsor.

6. For participants in dose escalation only: Histologically confirmed solid tumours
(except primary CNS tumours) that are unresectable, locally advanced, or metastatic
and have progressed following all standard treatments or is not appropriate for
standard treatments.

7. Must have at least one measurable lesion based on 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. 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 participant 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 anaesthesia must be completed at least 14 days
before IP administration. Surgery requiring local/epidural anaesthesia must be
completed at least 72 hours before IP administration and participants should be
recovered.

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

Neutrophils = 1000/µL Platelets = 75,000/µL Haemoglobin = 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 participants with Gilbert's syndrome, who must have total bilirubin < 3.0
mg/dL).

12. Women must meet 1 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
participant. 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 the Expansion Cohort, participants enrolling must also meet the following
inclusion criteria:

Confirmed diagnosis of one of the following tumour types:

1. For all Expansion Cohorts (B1, B2, B2 reserve, and B3), histologically confirmed
advanced solid tumours (except primary CNS tumours) that are unresectable, locally
advanced, or metastatic and have progressed following all standard treatments, or are
not appropriate for standard treatments.

2. For the B3 cohort, participants must meet one of the following:

- Participants must have progressed following at least one line of standard
systemic therapy and there must not be other approved/standard therapy available
that has been shown to prolong overall survival (i.e., in a randomized trial
against another standard treatment or by comparison to historical controls);
participants who cannot receive other standard therapy that has been shown to
prolonged survival due to medical issues will be eligible, if other eligibility
criteria are met; OR

- Participants for whom no standard treatment exists that has been shown to prolong
overall survival.

The following tumour types are eligible for the B3 cohort:

- Metastatic NSCLC: Histologically or cytologically confirmed diagnosis of stage IV NSCLC
(cases of non-squamous cell carcinoma or NSCLC of unknown subtype) with high (= 50%) PD-L1
tumour expression as determined by IHC, without EGFR sensitizing (activating) mutation by
PCR and anaplastic lymphoma kinase (ALK) translocation as determined by IHC or fluorescence
in situ hybridization (FISH). For pathologically confirmed squamous cell carcinoma, only
high (= 50%) PD-L1 tumour expression is required.

For Korea only, participants may be enrolled, provided all of the following requirements
are met:

- Participants who have failed standard care of anti-cancer treatments, including
platinum-based chemotherapy.

- Participants who have refused or discontinued platinum-based chemotherapy due to
intolerance.

- Participants who have refused the approved immune checkpoint inhibitors as standard
treatment or discontinued due to intolerance. c. Unresectable or metastatic solid
tumours with MSI-H or dMMR, locally confirmed by polymerase chain reaction (PCR) or
any other appropriate method, such as IHC, in accordance with local site practices:

No additional MSI-H test is required if this test has been completed previously. However,
if the participant did not proceed with this test, then additional testing should be
completed at a local facility.

d. Histologically confirmed diagnosis of non-clear cell renal cell carcinoma (RCC), anal
squamous cell carcinoma (aSCC), uterine cervical cancer, cutaneous squamous cell carcinoma
of the skin (cSCC), uterine endometrial carcinoma, tumours which are tumour mutational
burden-high (TMB-H), epithelial tumour of the penis (squamous cell carcinoma or
adenocarcinoma), neuroendocrine tumour (any origin, pancreatic or non-pancreatic), and
nasopharyngeal cancers.

TMB-H: = 10 mutations/megabase, determined at the local (site) laboratory is acceptable for
study enrolment.

e. Histologically or cytologically confirmed recurrent or metastatic HNSCC.
Minimum age
18 Years
Maximum age
No limit
Sex
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 l.ng 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 participants with vitiligo or resolved childhood asthma/atopy.

10. Receipt of live, attenuated vaccine within 28 days prior to the first dose of IP
(Note: Participants, 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. Patients may receive vaccination
for SARS-CoV-2 (DNA or mRNA vaccine) at the discretion of the Investigator as soon as
they are eligible, and a vaccine is available.

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 participant inappropriate for entry into
the study.

14. Concurrent medical condition requiring the use of immunosuppressive medications or
immunosuppressive doses of systemic corticosteroids (doses 10 mg/day prednisone or
equivalent). Inhaled or intranasal corticosteroids (with minimal systemic absorption)
may be continued if the participant 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 participant must be sufficiently recovered and stable before treatment
administration.

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

18. Participant 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. Participant has a QT interval corrected using Fridericia's formula (QTcF) > 470 msec.
Participant has a history of prolonged QT syndrome or Torsades de pointes. Participant
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/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2023
Actual
Sample size
Target
90
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
Seongnam-si
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul
Country [3] 0 0
Thailand
State/province [3] 0 0
Bangkok

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 1/2a, open-label, multicenter, dose-escalation/dose-expansion study of
YBL-006, in participants with Advanced Solid Tumors. This multicenter study will be conducted
in approximately 11-14 participants in the dose escalation phase, and approximately 39-76
participants in dose expansion phase.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04450901
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yoon Jaebong
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
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/ct2/show/NCT04450901