Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04450901
Recruitment Status : Not yet recruiting
First Posted : June 30, 2020
Last Update Posted : June 30, 2020
Sponsor:
Collaborator:
Novotech (Australia) Pty Limited
Information provided by (Responsible Party):
Y Biologics Inc.

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: YBL-006 Phase 1

Detailed Description:

study will consist of three periods:

  1. Screening (up to 28 days)
  2. Treatment (28-day cycles)
  3. Follow-up (up to 3 months)

Dose Escalation:

An accelerated titration design will be utilized for the lowest dose cohort (0.5 mg/kg) in the dose escalation part. Whereas the traditional 3 + 3 design will be utilized for the higher dose cohorts until the RP2D is determined.

Expansion Cohorts:

Enrollment in expansion cohort will begin when the RP2D has been identified by the CoRC. Up to four tumor-specific cohorts consisting of approximately 16-20 patients per cohort will evaluate the safety, efficacy, PK, and PD of YBL-006 at the RP2D.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Single Arm, Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors
Estimated Study Start Date : July 1, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022

Arm Intervention/treatment
Experimental: Cohort A1 group
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg
Drug: YBL-006
Route of Administration: IV infusion; 0.5 mg/kg Q2W
Other Name: Cohort A1

Experimental: Cohort A2 group
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg
Drug: YBL-006
Route of Administration: IV infusion; 2 mg/kg Q2W
Other Name: Cohort A2

Experimental: Cohort A3 group
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg
Drug: YBL-006
Route of Administration: IV infusion; 5 mg/kg Q2W
Other Name: Cohort A3

Experimental: Cohort A4 group
YBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg
Drug: YBL-006
Route of Administration: IV infusion; 10 mg/kg Q2W
Other Name: Cohort A4




Primary Outcome Measures :
  1. Safety and tolerability measure through Adverse Events/Serious Adverse Events [ Time Frame: Measurements at Baseline till Follow up from 90 days of last dose ]
    Treatment-related adverse events as assessed by CTCAE v5.0 or higher

  2. Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure [ Time Frame: Measurements at Baseline till Follow up from 90 days of last dose ]
    Measured by result of the Vital Sign- blood pressure

  3. Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate [ Time Frame: Measurements at Baseline till Follow up from 90 days of last dose ]
    Measured by result of the Vital Sign- heart rate

  4. Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG [ Time Frame: Measurements at Baseline till Follow up from 90 days of last dose ]
    Measured by result of the ECG QT Interval

  5. Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam [ Time Frame: Measurements at Baseline till Follow up from 90 days of last dose ]
    Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.

  6. To establish the recommended Phase 2 dose (RP2D) of YBL-006 in patients with advanced solid tumors [ Time Frame: Measurements at Baseline ]
    Measured through increase in anti-drug antibody (ADA) levels


Secondary Outcome Measures :
  1. pharmacokinetic (PK) profile of YBL-006 [ Time Frame: Measured at C1D1 till Follow up from 90 days of last dose ]
    PK is assessed by parameter- area under the curve (AUC)

  2. pharmacokinetic (PK) profile of YBL-006 [ Time Frame: Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose ]
    PK is assessed by parameter- maximum (or peak) serum concentration (Cmax)

  3. pharmacokinetic (PK) profile of YBL-006 [ Time Frame: Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose ]
    PK is assessed by parameter- time of peak concentration (Tmax)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04450901


Contacts
Layout table for location contacts
Contact: Myungsuk Kim -2-558-5383 ext +82 mskim@ybiologics.com

Locations
Layout table for location information
Australia, New South Wales
Macquarie University
Macquarie, New South Wales, Australia, 2109
Contact: Dhanusha Sabanathan    298122956 ext +61      
Principal Investigator: Dhanusha Sabanathan         
Korea, Republic of
Seoul National University Bundang Hospital
Gyeonggi-do, Korea, Republic of, 13605
Contact: Keun-Wook Lee    317878203 ext +82    springliz@daum.net   
Principal Investigator: Keun-Wook Lee         
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Contact: DoYoun Oh    260725174 ext +82    galaxy1222@naver.com   
Principal Investigator: DoYoun Oh         
Sponsors and Collaborators
Y Biologics Inc.
Novotech (Australia) Pty Limited
Investigators
Layout table for investigator information
Study Director: Myungsuk Kim Y-Biologics
Layout table for additonal information
Responsible Party: Y Biologics Inc.
ClinicalTrials.gov Identifier: NCT04450901    
Other Study ID Numbers: YBL006C101
First Posted: June 30, 2020    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms