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QUILT-3.051: NANT Ovarian Cancer Vaccine: Combination Immunotherapy in Subjects With Epithelial Ovarian Cancer Who Have Progressed on or After Standard-of-care (SoC) Therapy

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: NCT03197584
Recruitment Status : Withdrawn (Trial not initiated)
First Posted : June 23, 2017
Last Update Posted : March 18, 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 epithelial ovarian cancer who have progressed on or after SoC therapy.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Biological: Avelumab Biological: Bevacizumab Drug: Capecitabine Drug: Cyclophosphamide Drug: 5-fluorouracil Drug: Fulvestrant Drug: Leucovorin Drug: Paclitaxel Drug: omega-3 acid ethyl esters Drug: Oxaliplatin Radiation: Stereotactic Body Radiation Therapy Biological: ALT-803 Biological: ETBX-021 Biological: ETBX-051 Biological: ETBX-061 Biological: GI-4000 Biological: GI-6301 Biological: haNK® Phase 1 Phase 2

Detailed Description:
Treatment will be administered in two phases, an induction and a maintenance phase. Subjects will continue induction treatment for up to 1 year or until they experience progressive disease (PD) or unacceptable toxicity (not correctable with dose reduction), withdraw 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 in 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. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.

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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 Ovarian Cancer Vaccine: Combination Immunotherapy in Subjects With Epithelial Ovarian Cancer Who Have Progressed on or After Standard-of-care (SoC) Therapy
Estimated Study Start Date : December 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arm Intervention/treatment
Experimental: NANT Ovarian Cancer Vaccine
avelumab, bevacizumab, capecitabine, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, paclitaxel, omega-3-acid ethyl esters, oxaliplatin, stereotactic body radiation therapy, ALT-803, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6301, and hank®.
Biological: Avelumab
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Biological: Bevacizumab
Recombinant human anti-VEGF IgG1 monoclonal antibody

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

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

Drug: 5-fluorouracil
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: 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

Drug: omega-3 acid ethyl esters
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
Stereotactic Body Radiation Therapy (SBRT)

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

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

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

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

Biological: GI-4000
Heat-killed S. cerevisiae yeast expressing the mutated RAS oncoproteins

Biological: GI-6301
Heat-killed S. cerevisiae yeast expressing the human Brachyury (hBrachyury) oncoprotein

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

Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (AEs) and serious AE (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

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

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

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

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

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

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

  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

  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

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

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

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

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 IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed epithelial ovarian cancer that has progressed on or after SoC therapy. Germ cell, stromal, and borderline ovarian tumors are not allowed.
  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 tumor biopsy specimen following the conclusion of the most recent anticancer treatment. If a 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 for controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, and cervical); 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 < 3,000 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), 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.
  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: NCT03197584    
Other Study ID Numbers: QUILT-3.051
First Posted: June 23, 2017    Key Record Dates
Last Update Posted: March 18, 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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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents