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QUILT-3.090: NANT Squamous Cell Carcinoma (SCC) Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With SCC Who Have Progressed on or After Platinum-based Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy

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ClinicalTrials.gov Identifier: NCT03387111
Recruitment Status : Recruiting
First Posted : December 29, 2017
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
NantKwest, Inc.

Brief Summary:
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with SCC who have progressed on or after previous platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. Phase 2 will be based on Simon's two-stage optimal design.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma Drug: Aldoxorubicin HCl 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 for infusion Biological: avelumab Biological: bevacizumab Drug: Capecitabine Drug: Cetuximab Drug: Cisplatin Drug: Cyclophosphamide Drug: Fluorouracil Drug: Leucovorin Drug: nab-Paclitaxel Drug: Necitumumab Procedure: SBRT 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 corrected 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 who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's and Sponsor's discretion. Subjects may remain in the maintenance phase of the study for up to 1 year. The duration of the maintenance phase can exceed 1 year if the subject continues to benefit, per the Investigator's and Sponsor's discretion. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The time on study treatment, including both the induction and maintenance phases, is up to 2 years. The duration of the study may exceed 2 years if the subject remains in the maintenance phase for more than 1 year, as described above.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NANT Squamous Cell Carcinoma (SCC) Vaccine: Molecularly Informed Integrated Immunotherapy Combining Innate High-affinity Natural Killer (haNK) Cell Therapy With Adenoviral and Yeast-based Vaccines to Induce T-cell Responses in Subjects With SCC Who Have Progressed on or After Platinum-based Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy
Actual Study Start Date : January 13, 2018
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: NANT Squamous Cell Carcinoma (SCC) Vaccine
A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
Drug: Aldoxorubicin HCl
Aldoxorubicin hydrochloride

Biological: ALT-803
Recombinant human super agonist interleukin-15 (IL-15) complex

Biological: ETBX-011
Ad5 [E1-, E2b-]-CEA

Biological: ETBX-021
Ad5 [E1-, E2b-]-HER2

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

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

Biological: GI-4000
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Biological: GI-6207
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins

Biological: GI-6301
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins

Biological: haNK for infusion
NK-92 [CD16.158V, ER IL-2]

Biological: avelumab
Recombinant human anti-PD-L1 IgG1 monoclonal antibody

Biological: bevacizumab
Recombinant human anti-VEGF IgG1 monoclonal

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

Drug: Cetuximab
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.

Drug: Cisplatin
cis-diamminedichloroplatinum(II)

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

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

Drug: Leucovorin
L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt

Drug: nab-Paclitaxel
Benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-y1ester,(αR,βS)-(9CI) bound to albumin

Drug: Necitumumab
Necitumumab is a recombinant human lgG1 monoclonal antibody.

Procedure: SBRT
Stereotactic Body Radiation Therapy




Primary Outcome Measures :
  1. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03. [ Time Frame: 8 weeks ]
    Phase 1b primary endpoint

  2. Objective response rate by RECIST [ Time Frame: 1 year ]
    Phase 2 primary endpoint


Secondary Outcome Measures :
  1. Objective response rate by RECIST [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  2. Objective response rate by irRC [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  3. Progression-free survival by RECIST during Phase 1b [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  4. Progression-free survival by irRC during Phase 1b [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  5. Overall survival [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  6. Duration of response by RECIST and irRC [ Time Frame: 1 year ]
    Phase 1b secondary endpoint

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

  8. Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint

  9. Objective response rate by irRC [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  10. Progression-free survival by RECIST during Phase 2 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  11. Progression-free survival by irRC during Phase 2 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  12. Overall survival [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  13. Duration of response by RECIST and irRC [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  14. Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months) by RECIST and irRC. [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  15. Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 1 year ]
    Phase 2 secondary endpoint

  16. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03. [ Time Frame: 1 year ]
    Phase 2 secondary endpoint



Information from the National Library of Medicine

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

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 HNSCC or squamous NSCLC with progression on or after platinum-based 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 ≥ 1.0 cm.
  6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 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, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
  7. Must be willing to provide blood samples prior to the start of treatment on this study.
  8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, if considered safe by the Investigator.
  9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  10. 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. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria:

  1. 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.
  2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).
  3. History of organ transplant requiring immunosuppression.
  4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  5. Inadequate organ function, evidenced by the following laboratory results:

    1. Absolute neutrophil count < 1,000 cells/mm3.
    2. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
    3. Platelet count < 75,000 cells/mm3.
    4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    6. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.
  6. 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. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
  7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of predicted normal.
  8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  9. Positive results of screening test for human immunodeficiency virus (HIV).
  10. 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.
  11. Known hypersensitivity to any component of the study medication(s).
  12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  13. 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.
  14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  15. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.
  16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  17. Concurrent participation in any interventional clinical trial.
  18. Pregnant and nursing women.

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): NCT03387111


Contacts
Contact: NantKWest Clinical Review Team 310-853-7562 clinical.trials@NantKwest.com

Locations
United States, California
Chan Soon-Shiong Institute for Medicine Recruiting
El Segundo, California, United States, 90245
Sponsors and Collaborators
NantKwest, Inc.

Responsible Party: NantKwest, Inc.
ClinicalTrials.gov Identifier: NCT03387111     History of Changes
Other Study ID Numbers: QUILT-3.090
First Posted: December 29, 2017    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Vaccines
Cyclophosphamide
Fluorouracil
Paclitaxel
Cisplatin
Bevacizumab
Capecitabine
Cetuximab
Doxorubicin
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating