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QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and PD-1/PD-L1 Therapy

Primary Purpose

Urothelial Carcinoma

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
avelumab
bevacizumab
capecitabine
cisplatin
cyclophosphamide
5Fluorouracil (5-FU)
fulvestrant
leucovorin
nab-paclitaxel
Lovaza
Stereotactic Body Radiation Therapy
ALT-803
ETBX-011
ETBX-021
ETBX-051
ETBX-061
GI-4000
GI-6207
GI-6301
haNK
Sponsored by
ImmunityBio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urothelial Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed urothelial cancer with progression on or after chemotherapy and anti-PD-1/PD-L1 therapy.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  5. Have at least 1 measurable lesion of ≥ 1.5 cm.
  6. Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
  7. Must be willing to provide blood samples and, if considered safe by the Investigator, a tumor biopsy specimen at 8 weeks after the start of treatment.
  8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  9. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment.

Exclusion Criteria:

  1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
  2. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); and bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature.
  3. 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.
  4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
  5. History of organ transplant requiring immunosuppression.
  6. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  7. Requires whole blood transfusion to meet eligibility criteria.
  8. Inadequate organ function, evidenced by the following laboratory results:

    1. White blood cell (WBC) count < 3,500 cells/mm3.
    2. Absolute neutrophil count < 1,500 cells/mm3.
    3. Platelet count < 100,000 cells/mm3.
    4. Hemoglobin < 9 g/dL.
    5. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    6. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    7. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    8. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    9. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
  9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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.
  10. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  12. 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.
  13. Known hypersensitivity to any component of the study medication(s).
  14. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  15. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.
  16. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  17. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
  18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  19. Concurrent participation in any interventional clinical trial.
  20. Pregnant and nursing women.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Nant Urothelial Cancer Vaccine

    Arm Description

    avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.

    Outcomes

    Primary Outcome Measures

    Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
    Phase 1b primary endpoint (safety)
    Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Phase 2 primary endpoint (ORR by RECIST)
    ORR by Immune-related response criteria (irRC)
    Phase 2 primary endpoint (ORR by irRC)

    Secondary Outcome Measures

    ORR by RECIST Version 1.1
    Phase 1b secondary endpoint (ORR by RECIST)
    ORR by irRC
    Phase 1b secondary endpoint (ORR by irRC)
    Progression-free survival (PFS) by RECIST Version 1.1
    Phase 1b and 2 secondary endpoint (PFS by RECIST)
    PFS by irRC
    Phase 1b and 2 secondary endpoint (PFS by irRC)
    Overall survival (OS): time from the date of first treatment to the date of death (any cause)
    Phase 1b and 2 secondary endpoint (OS)
    Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first
    Phase 1b and 2 secondary endpoint (DR)
    Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months
    Phase 1b and 2 secondary endpoint (DCR)
    Patient-reported outcomes (PRO) using the using the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) instrument
    Phase 1b and 2 secondary endpoint (PRO)
    Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
    Phase 2 secondary endpoint (AEs)

    Full Information

    First Posted
    June 20, 2017
    Last Updated
    March 17, 2021
    Sponsor
    ImmunityBio, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03197571
    Brief Title
    QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and PD-1/PD-L1 Therapy
    Official Title
    QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2017
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Trial not initiated
    Study Start Date
    December 2017 (Anticipated)
    Primary Completion Date
    January 2019 (Anticipated)
    Study Completion Date
    March 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    ImmunityBio, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with urothelial cancer who have progressed on or after chemotherapy and anti- PD-1/PD-L1 therapy.
    Detailed Description
    The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each subject to enable the assessment of any acute and subacute toxicities, unless data are available from other NANT cancer vaccine studies suggesting the combination therapy is tolerable. Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Urothelial Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Nant Urothelial Cancer Vaccine
    Arm Type
    Experimental
    Arm Description
    avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
    Intervention Type
    Biological
    Intervention Name(s)
    avelumab
    Intervention Description
    Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
    Intervention Type
    Biological
    Intervention Name(s)
    bevacizumab
    Intervention Description
    Recombinant human anti-vascular endothelial growth factor (VEGF) IgG1 monoclonal antibody
    Intervention Type
    Drug
    Intervention Name(s)
    capecitabine
    Intervention Description
    5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
    Intervention Type
    Drug
    Intervention Name(s)
    cisplatin
    Intervention Description
    (SP-4-2)-diamminedichloroplatinum(II)
    Intervention Type
    Drug
    Intervention Name(s)
    cyclophosphamide
    Intervention Description
    2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
    Intervention Type
    Drug
    Intervention Name(s)
    5Fluorouracil (5-FU)
    Intervention Description
    5-fluoro-2,4 (1H,3H)-pyrimidinedione
    Intervention Type
    Drug
    Intervention Name(s)
    fulvestrant
    Intervention Description
    7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol
    Intervention Type
    Drug
    Intervention Name(s)
    leucovorin
    Intervention Description
    Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)
    Intervention Type
    Drug
    Intervention Name(s)
    nab-paclitaxel
    Intervention Description
    5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
    Intervention Type
    Drug
    Intervention Name(s)
    Lovaza
    Intervention Description
    Omega-3-acid ethyl esters
    Intervention Type
    Radiation
    Intervention Name(s)
    Stereotactic Body Radiation Therapy
    Intervention Description
    (SBRT)
    Intervention Type
    Biological
    Intervention Name(s)
    ALT-803
    Intervention Description
    recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]
    Intervention Type
    Biological
    Intervention Name(s)
    ETBX-011
    Intervention Description
    adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    ETBX-021
    Intervention Description
    Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    ETBX-051
    Intervention Description
    Ad5 [E1-, E2b-]-Brachyury vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    ETBX-061
    Intervention Description
    Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    GI-4000
    Intervention Description
    RAS yeast vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    GI-6207
    Intervention Description
    CEA yeast vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    GI-6301
    Intervention Description
    Brachyury yeast vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    haNK
    Intervention Description
    NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion (haNK™ for Infusion)
    Primary Outcome Measure Information:
    Title
    Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
    Description
    Phase 1b primary endpoint (safety)
    Time Frame
    1 year
    Title
    Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Description
    Phase 2 primary endpoint (ORR by RECIST)
    Time Frame
    1 year
    Title
    ORR by Immune-related response criteria (irRC)
    Description
    Phase 2 primary endpoint (ORR by irRC)
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    ORR by RECIST Version 1.1
    Description
    Phase 1b secondary endpoint (ORR by RECIST)
    Time Frame
    1 year
    Title
    ORR by irRC
    Description
    Phase 1b secondary endpoint (ORR by irRC)
    Time Frame
    1 year
    Title
    Progression-free survival (PFS) by RECIST Version 1.1
    Description
    Phase 1b and 2 secondary endpoint (PFS by RECIST)
    Time Frame
    2 years
    Title
    PFS by irRC
    Description
    Phase 1b and 2 secondary endpoint (PFS by irRC)
    Time Frame
    2 years
    Title
    Overall survival (OS): time from the date of first treatment to the date of death (any cause)
    Description
    Phase 1b and 2 secondary endpoint (OS)
    Time Frame
    2 years
    Title
    Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first
    Description
    Phase 1b and 2 secondary endpoint (DR)
    Time Frame
    2 years
    Title
    Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months
    Description
    Phase 1b and 2 secondary endpoint (DCR)
    Time Frame
    2 months
    Title
    Patient-reported outcomes (PRO) using the using the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) instrument
    Description
    Phase 1b and 2 secondary endpoint (PRO)
    Time Frame
    2 years
    Title
    Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
    Description
    Phase 2 secondary endpoint (AEs)
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines. Histologically-confirmed urothelial cancer with progression on or after chemotherapy and anti-PD-1/PD-L1 therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Have at least 1 measurable lesion of ≥ 1.5 cm. Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period. Must be willing to provide blood samples and, if considered safe by the Investigator, a tumor biopsy specimen at 8 weeks after the start of treatment. 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 non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Exclusion Criteria: History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); and bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. 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. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma). History of organ transplant requiring immunosuppression. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). Requires whole blood transfusion to meet eligibility criteria. Inadequate organ function, evidenced by the following laboratory results: White blood cell (WBC) count < 3,500 cells/mm3. Absolute neutrophil count < 1,500 cells/mm3. Platelet count < 100,000 cells/mm3. Hemoglobin < 9 g/dL. Total bilirubin greater than 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. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation). Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). 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). Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer. 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.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and PD-1/PD-L1 Therapy

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