Clinical Trials /

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

NCT04450901

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Multicenter, Single Arm, Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: YBL006C101
  • NCT ID: NCT04450901

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
YBL-006Cohort A1Cohort A1 group
YBL-006Cohort A2Cohort A2 group
YBL-006Cohort A3Cohort A3 group
YBL-006Cohort A4Cohort A4 group

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A1 groupExperimentalYBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg
  • YBL-006
Cohort A2 groupExperimentalYBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg
  • YBL-006
Cohort A3 groupExperimentalYBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg
  • YBL-006
Cohort A4 groupExperimentalYBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg
  • YBL-006

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:pharmacokinetic (PK) profile of YBL-006
Time Frame:Measured at C1D1 till Follow up from 90 days of last dose
Safety Issue:
Description:PK is assessed by parameter- area under the curve (AUC)
Measure: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
Safety Issue:
Description:PK is assessed by parameter- maximum (or peak) serum concentration (Cmax)
Measure: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
Safety Issue:
Description:PK is assessed by parameter- time of peak concentration (Tmax)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Y Biologics Inc.

Last Updated

June 24, 2020