QUILT-3.067: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With TNBC Who Have Progressed on or After Standard-of-care Therapy.

NCT03387085 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: QUILT-3.067
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)

  Graded using the NCI CTCAE Version 4.03.

  Up to 2 years

Secondary Outcomes (10)

• Objective Response Rate by RECIST v1.1

  Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years

• Objective Response Rate by irRC (Percent of Subjects With Confirmed Complete or Partial Overall Response)

  Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years.

• Progression Free Survival by RECIST v1.1

  Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first. Up to 2.5 years.

• Progression Free Survival by irRC

  Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.

• Duration of Response by RECIST Version 1.1

  Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.

Study Arms (1)

NANT triple negative breast cancer (TNBC) Vaccine

EXPERIMENTAL

A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.

Drug: Aldoxorubicin HCl; Biological: N-803; Biological: ETBX-011; 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: Cisplatin; Drug: Cyclophosphamide; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Procedure: SBRT

Interventions

Aldoxorubicin HCl DRUG

Aldoxorubicin hydrochloride

NANT triple negative breast cancer (TNBC) Vaccine

N-803 BIOLOGICAL

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

NANT triple negative breast cancer (TNBC) Vaccine

ETBX-011 BIOLOGICAL

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

NANT triple negative breast cancer (TNBC) Vaccine

ETBX-051 BIOLOGICAL

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

NANT triple negative breast cancer (TNBC) Vaccine

ETBX-061 BIOLOGICAL

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

NANT triple negative breast cancer (TNBC) Vaccine

GI-4000 BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

NANT triple negative breast cancer (TNBC) Vaccine

GI-6207 BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins

NANT triple negative breast cancer (TNBC) Vaccine

GI-6301 BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins

NANT triple negative breast cancer (TNBC) Vaccine

haNK for Infusion BIOLOGICAL

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

NANT triple negative breast cancer (TNBC) Vaccine

avelumab BIOLOGICAL

Recombinant human anti-PD-L1 IgG1 monoclonal antibody

NANT triple negative breast cancer (TNBC) Vaccine

bevacizumab BIOLOGICAL

Recombinant human anti-VEGF IgG1 monoclonal

NANT triple negative breast cancer (TNBC) Vaccine

Capecitabine DRUG

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

NANT triple negative breast cancer (TNBC) Vaccine

Cisplatin DRUG

cis-diamminedichloroplatinum(II)

NANT triple negative breast cancer (TNBC) Vaccine

Cyclophosphamide DRUG

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

NANT triple negative breast cancer (TNBC) Vaccine

5-Fluorouracil DRUG

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

NANT triple negative breast cancer (TNBC) Vaccine

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

NANT triple negative breast cancer (TNBC) Vaccine

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

NANT triple negative breast cancer (TNBC) Vaccine

SBRT PROCEDURE

Stereotactic Body Radiation Therapy

NANT triple negative breast cancer (TNBC) Vaccine

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 old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
• Histologically-confirmed metastatic or unresectable TNBC that has either progressed on or after anthracycline-based chemotherapy (or other approved standard of care therapy) or subject has refused anthracycline-based chemotherapy, or other taxane- and platinum-based therapies. TNBC is defined as breast cancer that lacks estrogen receptor (ER) and progesterone receptor (PR) 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 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.
• Must be willing to provide blood samples prior to the start of treatment on this study.
• Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, if considered safe by the Investigator.
• 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, autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count \< 1000 cells/mm3.
• Platelet count \< 75,000 cells/mm3.
• 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 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. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
• Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (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

ALT-803; yeast-CEA vaccine; avelumab; Bevacizumab; Capecitabine; Cisplatin; Cyclophosphamide; Fluorouracil; Leucovorin; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@immunitybio.com

855-797-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: March 19, 2018
• Primary Completion: September 11, 2020
• Study Completion: January 16, 2024
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-08

Locations

US (1)