QUILT-3.057: NANT Neoadjuvant Triple- Negative Breast Cancer (TNBC) Vaccine

NCT ID: NCT03554109

Last Updated: 2025-02-21

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

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-30

Study Completion Date

2022-02-09

Brief Summary

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This is a randomized open-label phase 2 study to evaluate the efficacy and safety (as assessed by pCR) of the NANT Neoadjuvant TNBC Vaccine regimen (experimental arm) compared to the SoC dose-dense regimen of doxorubicin/cyclophosphamide followed by paclitaxel (control arm).

Detailed Description

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Treatment will be administered in 2 phases, a neoadjuvant phase and a postoperative phase. The neoadjuvant phase will be 18 weeks for patients enrolled in the experimental arm and 16 weeks for those enrolled in the control arm.

Following the neoadjuvant phase, all subjects will undergo determination of their current response status and appropriate breast surgery and node dissection after which assessment for pCR will be conducted following completion of neoadjuvant systemic therapy. Pathologists interpreting surgical specimens for pCR assessment will be blinded to the treatment arm.

All subjects, regardless of whether or not they have achieved a pCR, will then enter the postoperative phase where they will receive adjuvant treatment. A small portion of the corresponding neoadjuvant therapy, either nab-paclitaxel or paclitaxel, will be administered as adjuvant treatment postoperatively. Adjuvant treatment will continue in the postoperative phase until the subject experiences 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

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Triple Negative Breast Cancer (TNBC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Treatment will be administered in 2 phases, a neoadjuvant phase and a postoperative phase. For the experimental arm, subjects will receive treatment in the neoadjuvant phase for six 3-week cycles (ie, 18 weeks total). For the control arm, subjects will receive neoadjuvant treatment for a total of 16 weeks.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A

NANT Neoadjuvant Triple Negative Breast Cancer Vaccine

A combination of agents will be administered to subjects in this study:

cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, avelumab, aldoxorubicin HCl, ALT-803, haNK, GI-4000, GI-6207, GI-6301, ETBX-011, ETBX-051 and ETBX-061

Group Type EXPERIMENTAL

Leucovorin

Intervention Type DRUG

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

5-Fluorouracil

Intervention Type DRUG

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

Aldoxorubicin HCl

Intervention Type DRUG

albumin-binding prodrug of doxorubicin HCl

nab-Paclitaxel

Intervention Type DRUG

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

ETBX-011

Intervention Type BIOLOGICAL

Ad5 \[E1-, E2b-\]-CEA

ETBX-051

Intervention Type BIOLOGICAL

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

ETBX-061

Intervention Type BIOLOGICAL

Ad5 \[E1-, E2b-\]-mucin 1\[MUC1\]

GI-4000

Intervention Type BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

GI-6207

Intervention Type BIOLOGICAL

CEA yeast vaccine

GI-6301

Intervention Type BIOLOGICAL

Brachyury yeast vaccine

Avelumab

Intervention Type DRUG

Avelumab

ALT-803

Intervention Type BIOLOGICAL

Recombinant human super agonist interleukin-15 (IL-15) complex

haNK

Intervention Type BIOLOGICAL

NK-92 \[CD16.158V, ER IL-2\]

Cyclophosphamide

Intervention Type DRUG

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

Group B

Standard treatment with a combination of doxorubicin, cyclophosphamide and paclitaxel.

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

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

Doxorubicin HCL

Intervention Type DRUG

Doxorubicin HCL

paclitaxel

Intervention Type DRUG

paclitaxel

Interventions

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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

Intervention Type DRUG

5-Fluorouracil

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

Intervention Type DRUG

Aldoxorubicin HCl

albumin-binding prodrug of doxorubicin HCl

Intervention Type 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

Intervention Type DRUG

ETBX-011

Ad5 \[E1-, E2b-\]-CEA

Intervention Type BIOLOGICAL

ETBX-051

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

Intervention Type BIOLOGICAL

ETBX-061

Ad5 \[E1-, E2b-\]-mucin 1\[MUC1\]

Intervention Type BIOLOGICAL

GI-4000

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Intervention Type BIOLOGICAL

GI-6207

CEA yeast vaccine

Intervention Type BIOLOGICAL

GI-6301

Brachyury yeast vaccine

Intervention Type BIOLOGICAL

Avelumab

Avelumab

Intervention Type DRUG

ALT-803

Recombinant human super agonist interleukin-15 (IL-15) complex

Intervention Type BIOLOGICAL

haNK

NK-92 \[CD16.158V, ER IL-2\]

Intervention Type BIOLOGICAL

Cyclophosphamide

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

Intervention Type DRUG

Doxorubicin HCL

Doxorubicin HCL

Intervention Type DRUG

paclitaxel

paclitaxel

Intervention Type DRUG

Eligibility Criteria

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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 stage II or III TNBC. Subjects must be treatment naïve. TNBC is defined as breast cancer that lacks estrogen receptor (ER) and progesterone receptor (PgR) expression, and human epidermal growth factor receptor 2 (HER2) overexpression and/or amplification.
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 FFPE tumor biopsy specimen and be willing to release the specimen for prospective and exploratory tumor molecular profiling. 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.
7. Must be willing to provide blood samples prior to the start of treatment on this study for prospective tumor molecular profiling and exploratory analyses.
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. 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, and autoimmune disease associated with lymphoma).
3. History of organ transplant requiring immunosuppression.
4. History of or active inflammatory bowel disease (eg, Crohn's disease and ulcerative colitis).
5. Inadequate organ function, evidenced by the following laboratory results:

1. Absolute neutrophil count (ANC) \< 1,000 cells/mm\^3.
2. Platelet count \< 75,000 cells/mm\^3.
3. Uncorrectable grade 3 anemia (hemoglobin \< 8 g/dL).
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 (ALP) 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.
7. Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute 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 14 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ImmunityBio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chan Soon-Shiong Institute for Medicine

El Segundo, California, United States

Site Status

Countries

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United States

Other Identifiers

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QUILT-3.057

Identifier Type: -

Identifier Source: org_study_id

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