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

NCT03554109 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: QUILT-3.057
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Triple Negative Breast Cancer (TNBC)

Keywords

TNBC

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate

  Compare the efficacy of the NANT neoadjuvant TNBC Vaccine treatment vs standard-of-care (SoC) therapy as assessed by pathologic complete response (pCR) rate in the breast and axilla.

  8 months

Secondary Outcomes (5)

• Evaluation of safety as determined by incidence or treatment-emergent adverse events

  36 months

• Evaluate additional measures of efficacy by event-free survival

  36 months

• Overall survival

  36 months

• Locoregional relapse

  36 months

• Distant metastatic rates at 1 year

  36 months

Other Outcomes (1)

• Quality of life by patient-reported outcomes

  36 months

Study Arms (2)

Group A

EXPERIMENTAL

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

Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Aldoxorubicin HCl; Drug: nab-Paclitaxel; Biological: ETBX-011; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Drug: Avelumab; Biological: ALT-803; Biological: haNK; Drug: Cyclophosphamide

Group B

ACTIVE COMPARATOR

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

Drug: Cyclophosphamide; Drug: Doxorubicin HCL; Drug: paclitaxel

Interventions

Leucovorin 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

Group A

5-Fluorouracil DRUG

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

Group A

Aldoxorubicin HCl DRUG

albumin-binding prodrug of doxorubicin HCl

Group A

nab-Paclitaxel 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

Group A

ETBX-011 BIOLOGICAL

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

Group A

ETBX-051 BIOLOGICAL

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

Group A

ETBX-061 BIOLOGICAL

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

Group A

GI-4000 BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Group A

GI-6207 BIOLOGICAL

CEA yeast vaccine

Group A

GI-6301 BIOLOGICAL

Brachyury yeast vaccine

Group A

Avelumab DRUG

Avelumab

Group A

ALT-803 BIOLOGICAL

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

Group A

haNK BIOLOGICAL

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

Group A

Cyclophosphamide DRUG

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

Group A; Group B

Doxorubicin HCL DRUG

Doxorubicin HCL

Group B

paclitaxel DRUG

paclitaxel

Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Have at least 1 measurable lesion of ≥ 1.0 cm.
• 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.
• Must be willing to provide blood samples prior to the start of treatment on this study for prospective tumor molecular profiling and exploratory analyses.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• 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.

You may not qualify if:

• 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.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, and autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease and ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count (ANC) \< 1,000 cells/mm\^3.
• Platelet count \< 75,000 cells/mm\^3.
• Uncorrectable grade 3 anemia (hemoglobin \< 8 g/dL).
• Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
• Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (ALT \[SGPT\]) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
• Serum anion gap \> 16 mEq/L or arterial blood with pH \< 7.3.
• 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.
• Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute LVEF 10% below the institution's lower limit of predicted normal.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (1)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Leucovorin; Fluorouracil; 130-nm albumin-bound paclitaxel; yeast-CEA vaccine; avelumab; ALT-803; Cyclophosphamide; Doxorubicin; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 12, 2018
• Study Start: September 1, 2018
• Primary Completion: June 1, 2020
• Study Completion: February 9, 2022
• Last Updated: February 21, 2025

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)