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QUILT-3.044: NANT Non-small Cell Lung Cancer (NSCLC) Vaccine: Combination Immunotherapy in Subjects With NSCLC Who Have Progressed After Treatment With PD-1/PD-L1 Inhibitors

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. Read our disclaimer for details. Identifier: NCT03169738
Recruitment Status : Withdrawn (Trial not initiated)
First Posted : May 30, 2017
Last Update Posted : March 19, 2021
Information provided by (Responsible Party):
ImmunityBio, Inc.

Brief Summary:
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with NSCLC who have progressed on or after treatment with PD-1/PD-L1 inhibitors.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Biological: avelumab Biological: Bevacizumab Drug: Capecitabine Drug: Cisplatin Drug: cyclophosphamide Drug: 5-Fluorouracil (5-FU) Drug: fulvestrant Drug: leucovorin Drug: nab paclitaxel Biological: nivolumab Drug: Lovaza Drug: Oxaliplatin Radiation: Stereotactic Body Radiation Therapy Biological: ALT-803 Biological: ETBX-011 Biological: ETBX-021 Biological: ETBX-051 Biological: ETBX-061 Biological: GI-4000 Biological: GI-6207 Biological: GI-6301 Biological: haNK Phase 1 Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NANT Non-small Cell Lung Cancer (NSCLC) Vaccine: Combination Immunotherapy in Subjects With NSCLC Who Have Progressed After Treatment With Programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Inhibitors
Estimated Study Start Date : February 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Nant NSCLC Vaccine
avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, nab paclitaxel, nivolumab, lovaza, oxaliplatin, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Biological: avelumab
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Biological: Bevacizumab
Recombinant human anti-vascular endothelial growth factor (VEGF) immunoglobulin (Ig) G1 monoclonal antibody

Drug: Capecitabine
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine

Drug: Cisplatin

Drug: cyclophosphamide
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

Drug: 5-Fluorouracil (5-FU)
5-fluoro-2,4 (1H,3H)-pyrimidinedione

Drug: fulvestrant
7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol

Drug: leucovorin
Calcium N-[p-[[[(6RS)-2-amino-5- formyl-5,6,7,8-tetrahydro-4-hydroxy-6- pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)

Drug: nab paclitaxel
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

Biological: nivolumab
Human anti-PD-1 IgG4 kappa monoclonal antibody

Drug: Lovaza
Omega-3-acid ethyl esters

Drug: Oxaliplatin
cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum

Radiation: Stereotactic Body Radiation Therapy

Biological: ALT-803
recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL15N72D:IL-15RαSu/IgG1 Fc complex]

Biological: ETBX-011
adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine

Biological: ETBX-021
Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine

Biological: ETBX-051
Ad5 [E1-, E2b-]-Brachyury vaccine

Biological: ETBX-061
Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine

Biological: GI-4000
Ras yeast vaccine

Biological: GI-6207
CEA yeast vaccine

Biological: GI-6301
Brachyury yeast vaccine

Biological: haNK
NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion

Primary Outcome Measures :
  1. 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. [ Time Frame: 1 year ]
    Phase 1b primary endpoint (safety)

  2. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by RECIST)

  3. ORR by Immune-related response criteria (irRC ) [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by irRC)

Secondary Outcome Measures :
  1. ORR by RECIST Version 1.1 [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by RECIST)

  2. ORR by irRC [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by irRC)

  3. Progression-free survival (PFS) by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by RECIST)

  4. PFS by irRC [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by irRC)

  5. Overall survival (OS): time from the date of first treatment to the date of death (any cause) [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (OS)

  6. 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 [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (DR)

  7. Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months [ Time Frame: 2 months ]
    Phase 1b and 2 secondary endpoint (DCR)

  8. Quality of life (QoL) by patient-reported outcome using the Functional Assessment of Cancer Therapy-Lung (FACT-L) [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (QoL)

  9. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03 [ Time Frame: 2 years ]
    Phase 2 secondary endpoint (AEs)

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.

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

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed NSCLC with progression on or after treatment with PD-1/PD-L1 inhibitors for their indicated usages.
  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 anti-cancer 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. History 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. Subjects with a history of another malignancy must have > 5 years without evidence of disease.
  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.
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Responsible Party: ImmunityBio, Inc. Identifier: NCT03169738    
Other Study ID Numbers: QUILT-3.044
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: March 19, 2021
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors