Clinical Trials /

QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors

NCT04898543

Description:

This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of M-CENK and N-803 for subcutaneous administration, cryopreserved in subjects with locally advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes subjects with newly diagnosed high-risk solid tumors who have not received prior treatment for high-risk tumors; and cohort 2 includes subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. The two cohorts will be conducted simultaneously.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors
  • Official Title: Phase 1 Open-Label Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.076
  • NCT ID: NCT04898543

Conditions

  • Metastatic Solid Tumor

Interventions

DrugSynonymsArms
M-CENK, Suspension for Infusion, Cryopreserved (M-CENK)Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors
N803Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors

Purpose

This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of M-CENK and N-803 for subcutaneous administration, cryopreserved in subjects with locally advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes subjects with newly diagnosed high-risk solid tumors who have not received prior treatment for high-risk tumors; and cohort 2 includes subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. The two cohorts will be conducted simultaneously.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Subjects newly diagnosedExperimentalCohort 1: Subjects newly diagnosed with high-risk solid tumors who have not received treatment.
    Cohort 2: Subjects with relapsed/refractory (r/r) solid tumorsExperimentalCohort 2: Subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies.
    • M-CENK, Suspension for Infusion, Cryopreserved (M-CENK)
    • N803

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Age ≥ 18 years old.
    
              -  Able to understand and provide a signed informed consent that fulfills the relevant
                 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
    
              -  Have histologically confirmed unresectable, locally advanced or metastatic solid
                 tumor.
    
              -  For subjects with genetic mutations or alterations in solid tumors (e.g. NSCLC,
                 pancreatic cancer, melanoma), the subjects must have received prior appropriate
                 disease specific targeted therapy and have progressed.
    
              -  For subjects with a history of HIV
    
              -  Subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and without a history of AIDS
                 defining opportunistic infections are eligible.
    
              -  For subjects with a history of HBV
    
              -  Subjects who are chronic carriers of HBV infection (HBsAg-positive, undetectable or
                 low HBV DNA, and normal ALT) who are not on HBV therapy, or in individuals who have
                 serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and
                 anti-HBc-positive), anti-HBV prophylaxis should be assessed prior to enrollment.
    
              -  Subjects with chronic HBV infection with active disease who meet the criteria for anti
                 HBV therapy should be on a suppressive antiviral therapy prior to enrollment.
    
              -  For subjects with a history of HCV
    
              -  Subjects with a history of HCV infection should have completed curative antiviral
                 treatment and have a HCV viral load below the limit of quantification are eligible.
    
              -  Subjects who are HCV Ab positive but HCV RNA negative due to prior treatment or
                 natural resolution are eligible.
    
              -  Subjects on concurrent HCV treatment and have HCV below the limit of quantification
                 are eligible.
    
            Note: Subjects who have a history of HIV/HBV/HCV or are seropositive will require
            Infectious Disease Marker (IDM) testing prior to apheresis collection.
    
              -  Subjects with previously treated and who currently have non-progressive brain
                 metastasis may participate in this study.
    
              -  Able to undergo an Apheresis procedure:
    
              -  Has adequate venous access
    
              -  Able to sit or recline for 5-6 hours with limited movement
    
              -  Hemoglobin must be ≥ 9.0 g/dL
    
              -  Platelet count must be ≥ 100 cells/mm3
    
              -  Vital signs must be within normal range
    
              -  Negative pregnancy test for females of childbearing potential.
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
    
            Cohort 2 subjects only:
    
              -  Have received treatment with at least 2 prior lines of therapy in the metastatic
                 setting or not be a candidate for therapy of proven efficacy for their disease. Prior
                 immune therapy and prior treatment with a checkpoint inhibitor as per FDA indication
                 for current standard of care therapy is allowed.
    
              -  Have at least 1 measurable lesion and/or non-measurable disease evaluable in
                 accordance with RECIST Version 1.1.
    
              -  Ability to attend required study visits and return for adequate follow-up, as required
                 by this protocol.
    
              -  Agreement to practice effective contraception for female subjects of child-bearing
                 potential and nonsterile males.
    
            Exclusion Criteria:
    
            Cohort 2 subjects only:
    
              -  Serious uncontrolled concomitant disease that would contraindicate the use of the
                 investigational drug used in this study or that would put the subject at high risk for
                 treatment- related complications.
    
              -  Currently receiving antibiotics for a recent infection.
    
              -  Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
                 disease, autoimmune disease associated with lymphoma) requiring medical treatment
    
              -  History of organ transplant requiring immunosuppression.
    
              -  History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
                 colitis), unless the inflammation is well controlled.
    
              -  Inadequate organ function, evidenced by the following laboratory results:
    
              -  Absolute neutrophil count (ANC) < 1500 cells/mm3.
    
              -  Platelet count < 100,000 cells/mm3.
    
              -  Hemoglobin < 9 g/dL.
    
              -  Total bilirubin greater than 1.5 x the upper limit of normal (ULN; unless the subject
                 has documented Gilbert's syndrome).
    
              -  Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5
                 × ULN (> 5 × ULN in subjects with liver metastases).
    
              -  Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
                 metastases, or >10 × ULN in subjects with bone metastases).
    
              -  Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    
            Note: Each site should use its own institution's upper limit of normal (ULN) to determine
            eligibility.
    
              -  For subjects who have received approved chemotherapy or approved immunotherapy, a
                 repeat CBC a least 14 days after completion of the treatment to demonstrate recovery
                 of counts to an ANC ≥1000 and Platelets ≥100,000 is required.
    
              -  For subjects who have received investigational chemotherapy or investigational
                 immunotherapy, a repeat CBC a least 30 days after completion of the treatment to
                 demonstrate recovery of counts to an ANC ≥ 1000 and Platelets ≥ 100,000 is required.
    
              -  Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
                 clinically significant (ie, active) cardiovascular disease, cerebrovascular
                 accident/stroke, or myocardial infarction within 6 months prior to first study
                 medication; unstable angina; congestive heart failure of New York Heart Association
                 grade 2 or higher; or serious cardiac arrhythmia requiring medication.
    
              -  Dyspnea at rest due to complications of advanced malignancy or other disease requiring
                 continuous oxygen therapy. Oxygen therapy on an as needed or intermittent basis is
                 allowed.
    
              -  Current chronic daily treatment (continuous for > 3 months) with systemic
                 corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
                 excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
                 reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
    
              -  Known hypersensitivity to any component of the study medication(s).
    
              -  Assessed by the Investigator to be unable or unwilling to comply with the requirements
                 of the protocol.
    
              -  Concurrent participation in any interventional clinical trial.
    
              -  Pregnant and nursing women. A negative serum pregnancy test during screening and a
                 negative pregnancy test within 72 hours prior to the first dose must be documented
                 before M-CENK is administered to a female subject of childbearing potential.
          
    Maximum Eligible Age:100 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Safety of apheresis collection
    Time Frame:from baseline to study day 1
    Safety Issue:
    Description:Safety of apheresis procedure for collection of 2 blood volumes. AEs and SAEs will be measured using CTCAE Version 5. For example, the incidence, severity, and management of AEs or SAEs will be reported.

    Secondary Outcome Measures

    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNCs for manufacturing M-CENK cells
    Time Frame:From baseline to Week 1
    Safety Issue:
    Description:Number of MNCs for manufacturing M-CENK cells.
    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNC collected and the percentage of NK Cells (CD56/CD16 positive cells)
    Time Frame:From baseline to Week 1
    Safety Issue:
    Description:Number of MNC collected and the percentage of NK Cells (CD56/CD16 positive cells) after a two blood volume apheresis procedure for collection. The cell count and viability will be measured using an automated cell counter. The percentage of cells that are CD56/CD16 positive will be measured using flow cytometry.
    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNC collected and the percentage of NK Cells (CD3 cells)
    Time Frame:From baseline to Week 1
    Safety Issue:
    Description:Number of MNC collected and the percentage of NK Cells (CD3 cells) after a two blood volume apheresis procedure for collection. The cell count and viability will be measured using an automated cell counter. The percentage of cells that are CD3 positive will be measured using flow cytometry.
    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Number, phenotype, and function of M-CENK cells
    Time Frame:from baseline to Week 4
    Safety Issue:
    Description:Number, phenotype, and function of M-CENK cells following enrichment and expansion of the NK cells ex-vivo. Phenotype and cell functionality will be measured using flow cytometry. The expected outcome is for a functional product with high viability.
    Measure:Study Endpoints (cohort 1 and cohort 2, part A subjects): Aliquot and manufacture cryopreserved M-CENK cells
    Time Frame:from baseline to Week 4
    Safety Issue:
    Description:Aliquot and manufacture cryopreserved M-CENK cells ahead of use in a clinical protocol adoptive transfer correlated with clinical end points.
    Measure:Study Endpoints (for cohort 2, part B subjects only): ORR
    Time Frame:through Day 203
    Safety Issue:
    Description:ORR in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and modified RECIST guidelines for immunotherapy trials (iRECIST)
    Measure:Study Endpoints (for cohort 2, part B subjects only): PFS
    Time Frame:through Day 203
    Safety Issue:
    Description:PFS by RECIST Version 1.1 and iRECIST
    Measure:Study Endpoints (for cohort 2, part B subjects only): OS
    Time Frame:through Day 203
    Safety Issue:
    Description:OS will be evaluated using Kaplan-Meier methods. OS will be defined as the time from the date of first treatment to the date of death (any cause). Subjects who are alive at the end of follow-up will be censored at the last known date alive.
    Measure:Study Endpoints (for cohort 2, part B subjects only): Laboratory tests
    Time Frame:through Day 203
    Safety Issue:
    Description:Incidence of abnormal changes of laboratory tests include hematology and chemistry panel
    Measure:Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Temperature
    Time Frame:through Day 203
    Safety Issue:
    Description:Changes in vital signs from Grades 1-4: measured in (°C) or (°F)
    Measure:Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Heart Rate
    Time Frame:through Day 203
    Safety Issue:
    Description:Changes in vital signs from Grades 1-4: measured by how many heart beats per minute
    Measure:Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Blood Pressure
    Time Frame:through Day 203
    Safety Issue:
    Description:Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg
    Measure:Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Oxygen Saturation
    Time Frame:through Day 203
    Safety Issue:
    Description:is measured by Pulse Oxymetry
    Measure:Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Respiratory Rate
    Time Frame:through Day 203
    Safety Issue:
    Description:Changes in vital signs from Grades 1-4: measured in how many breaths per minute

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:ImmunityBio, Inc.

    Last Updated

    June 3, 2021