QUILT-3.047: NANT Head and Neck Squamous Cell Carcinoma (HNSCC) Vaccine: Combination Immunotherapy in Subjects With HNSCC Who Have Progressed on or After Chemotherapy and PD-1/PD-L1 Therapy

NCT ID: NCT03169764

Last Updated: 2025-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-31

Study Completion Date

2021-12-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with HNSCC who have progressed on or after previous chemotherapy and anti-PD-1/PD-L1 therapy.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Head and Neck Squamous Cell Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Nant HNSCC Vaccine

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

Group Type EXPERIMENTAL

Avelumab

Intervention Type BIOLOGICAL

Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Bevacizumab

Intervention Type BIOLOGICAL

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

Capecitabine

Intervention Type DRUG

5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine

Cetuximab

Intervention Type BIOLOGICAL

Recombinant human/mouse chimeric anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody

Cisplatin

Intervention Type DRUG

(SP-4-2)-diamminedichloroplatinum(II)

cyclophosphamide

Intervention Type DRUG

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

5-Fluorouracil (5-FU)

Intervention Type DRUG

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

fulvestrant

Intervention Type DRUG

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

leucovorin

Intervention Type DRUG

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

nab-paclitaxel

Intervention Type DRUG

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

nivolumab

Intervention Type BIOLOGICAL

Human anti-PD-1 IgG4 kappa monoclonal antibody

Lovaza

Intervention Type DRUG

Omega-3-acid ethyl esters

Stereotactic Body Radiation Therapy

Intervention Type RADIATION

(SRBT)

ALT-803

Intervention Type BIOLOGICAL

recombinant human super agonist interleukin-15 (IL-15) complex \[also known as IL 15N72D:IL-15RαSu/IgG1 Fc complex\]

ETBX-011

Intervention Type BIOLOGICAL

adenovirus serotype-5 \[Ad5\] \[E1-, E2b-\]-carcinoembryonic antigen (CEA) vaccine

ETBX-021

Intervention Type BIOLOGICAL

Ad5 \[E1-, E2b-\]-human epidermal growth factor receptor 2 (HER2) vaccine

ETBX-051

Intervention Type BIOLOGICAL

Ad5 \[E1-, E2b-\]-Brachyury vaccine

ETBX-061

Intervention Type BIOLOGICAL

Ad5 \[E1-, E2b-\]-mucin 1 (MUC1) vaccine

GI-4000

Intervention Type BIOLOGICAL

Ras yeast vaccine

GI-6207

Intervention Type BIOLOGICAL

CEA yeast vaccine

GI-6301

Intervention Type BIOLOGICAL

Brachyury yeast vaccine

haNK

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Avelumab

Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Intervention Type BIOLOGICAL

Bevacizumab

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

Intervention Type BIOLOGICAL

Capecitabine

5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine

Intervention Type DRUG

Cetuximab

Recombinant human/mouse chimeric anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody

Intervention Type BIOLOGICAL

Cisplatin

(SP-4-2)-diamminedichloroplatinum(II)

Intervention Type DRUG

cyclophosphamide

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

Intervention Type DRUG

5-Fluorouracil (5-FU)

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

Intervention Type DRUG

fulvestrant

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

Intervention Type 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)

Intervention Type 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

Intervention Type DRUG

nivolumab

Human anti-PD-1 IgG4 kappa monoclonal antibody

Intervention Type BIOLOGICAL

Lovaza

Omega-3-acid ethyl esters

Intervention Type DRUG

Stereotactic Body Radiation Therapy

(SRBT)

Intervention Type RADIATION

ALT-803

recombinant human super agonist interleukin-15 (IL-15) complex \[also known as IL 15N72D:IL-15RαSu/IgG1 Fc complex\]

Intervention Type BIOLOGICAL

ETBX-011

adenovirus serotype-5 \[Ad5\] \[E1-, E2b-\]-carcinoembryonic antigen (CEA) vaccine

Intervention Type BIOLOGICAL

ETBX-021

Ad5 \[E1-, E2b-\]-human epidermal growth factor receptor 2 (HER2) vaccine

Intervention Type BIOLOGICAL

ETBX-051

Ad5 \[E1-, E2b-\]-Brachyury vaccine

Intervention Type BIOLOGICAL

ETBX-061

Ad5 \[E1-, E2b-\]-mucin 1 (MUC1) vaccine

Intervention Type BIOLOGICAL

GI-4000

Ras yeast vaccine

Intervention Type BIOLOGICAL

GI-6207

CEA yeast vaccine

Intervention Type BIOLOGICAL

GI-6301

Brachyury yeast vaccine

Intervention Type BIOLOGICAL

haNK

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

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 HNSCC 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 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.
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 for controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, and 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.

and Neck Squamous Cell Carcinoma Vaccine NantCell, Inc. Clinical Trial Protocol: QUILT-3.047
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, and autoimmune disease associated with lymphoma).
5. History of organ transplant requiring immunosuppression.
6. History of or active inflammatory bowel disease (eg, Crohn's disease and 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), 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

ImmunityBio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

QUILT-3.047

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Vaccination With Flt3L, Radiation, and Poly-ICLC
NCT03789097 RECRUITING PHASE1/PHASE2
A Study of a Personalized Neoantigen Cancer Vaccine
NCT03639714 COMPLETED PHASE1/PHASE2