- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03387085
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.
September 26, 2023 updated by: ImmunityBio, Inc.
NANT Triple Negative Breast Cancer (TNBC) Vaccine: Molecularly Informed Integrated Immunotherapy Combining Innate High-affinity Natural Killer (haNK) Cell Therapy With Adenoviral and Yeast-based Vaccines to Induce T-cell Responses in Subjects With TNBC Who Have Progressed on or After Standard-of-care Therapy.
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
- Biological: ETBX-051
- Drug: Leucovorin
- Drug: 5-Fluorouracil
- Drug: nab-Paclitaxel
- Biological: ETBX-011
- Biological: GI-4000
- Drug: Cyclophosphamide
- Drug: Capecitabine
- Biological: bevacizumab
- Biological: avelumab
- Biological: N-803
- Drug: Aldoxorubicin HCl
- Biological: ETBX-061
- Biological: GI-6207
- Biological: GI-6301
- Biological: haNK for Infusion
- Drug: Cisplatin
- Procedure: SBRT
Detailed Description
Treatment will be administered in two phases, an induction and a maintenance phase, as described below.
Subjects will continue induction treatment for up to 1 year.
Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws 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 who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's discretion.
Subjects may remain on 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 corrected 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.
Study Type
Interventional
Enrollment (Estimated)
79
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
El Segundo, California, United States, 90245
- Chan Soon-Shiong Institute for Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
- Positive results of screening test for human immunodeficiency virus (HIV).
- 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.
- Known hypersensitivity to any component of the study medication(s).
- Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
- 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.
- Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
- Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to initiation of treatment on this study, except for testosterone-lowering therapy in men with prostate cancer.
- Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
- Concurrent participation in any interventional clinical trial.
- Pregnant and nursing women.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NANT triple negative breast cancer (TNBC) Vaccine
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.
|
Ad5 [E1-, E2b-]-Brachyury vaccine
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-fluoro-2,4 (1H,3H)-pyrimidinedione
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
Ad5 [E1-, E2b-]-CEA
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
Recombinant human anti-VEGF IgG1 monoclonal
Recombinant human anti-PD-L1 IgG1 monoclonal antibody
Recombinant human super agonist interleukin-15 (IL-15) complex
Aldoxorubicin hydrochloride
Ad5 [E1-, E2b-]-MUC1
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins
NK-92 [CD16.158V, ER IL-2]
cis-diamminedichloroplatinum(II)
Stereotactic Body Radiation Therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Time Frame: 8 weeks
|
Phase 1b primary endpoint
|
8 weeks
|
Objective response rate by RECIST
Time Frame: 8 weeks
|
Phase 2 primary endpoint
|
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate by RECIST
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Objective response rate by irRC
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Progression-free survival by RECIST during Phase 1b
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Progression-free survival by irRC during Phase 1b
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Overall survival
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Patient-reported outcomes of pancreatic cancer symptoms
Time Frame: 8 weeks
|
Phase 1b secondary endpoint
|
8 weeks
|
Progression-free survival by RECIST during Phase 2
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Progression-free survival by irRC during Phase 2
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Overall survival
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Patient-reported outcomes of pancreatic cancer symptoms
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Duration of response by RECIST and irRC
Time Frame: 1 year
|
Phase 1b secondary endpoint
|
1 year
|
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months) by RECIST and irRC.
Time Frame: 1 year
|
Phase 1b secondary endpoint
|
1 year
|
Objective response rate by irRC
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Duration of response by RECIST and irRC
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months) by RECIST and irRC.
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Time Frame: 1 year
|
Phase 2 secondary endpoint
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 16, 2018
Primary Completion (Estimated)
September 1, 2023
Study Completion (Estimated)
October 1, 2023
Study Registration Dates
First Submitted
December 21, 2017
First Submitted That Met QC Criteria
December 21, 2017
First Posted (Actual)
December 29, 2017
Study Record Updates
Last Update Posted (Actual)
September 28, 2023
Last Update Submitted That Met QC Criteria
September 26, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Triple Negative Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Cyclophosphamide
- Paclitaxel
- Fluorouracil
- Capecitabine
- Bevacizumab
- Leucovorin
- Avelumab
Other Study ID Numbers
- QUILT-3.067
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Triple Negative Breast Cancer
-
Peregrine PharmaceuticalsWithdrawnBreast Cancer | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | Triple-Negative Breast Cancer | Triple-Negative Breast Neoplasm | ER-Negative PR-Negative HER2-Negative Breast Neoplasms | ER-Negative PR-Negative HER2-Negative Breast Cancer
-
Swiss Group for Clinical Cancer ResearchNot yet recruitingTriple-negative Breast Cancer | TNBC - Triple-Negative Breast CancerSwitzerland
-
Washington University School of MedicineNational Cancer Institute (NCI); National Institutes of Health (NIH); MedImmune...TerminatedTriple Negative Breast Cancer | Triple Negative Breast Neoplasms | TNBC - Triple-Negative Breast Cancer | Triple-negative Breast CarcinomaUnited States
-
G1 Therapeutics, Inc.TerminatedBreast Cancer | Breast Neoplasm | Triple-Negative Breast Cancer | Triple-Negative Breast NeoplasmsUnited States, Bulgaria, Croatia, Slovenia, Serbia, Belgium, North Macedonia, Slovakia
-
AkesoRecruitingMetastatic Triple-negative Breast Cancer | Locally Advanced Triple-negative Breast CancerChina
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
Fudan UniversityNot yet recruitingTriple-negative Breast Cancer
-
Fudan UniversityRecruitingTriple-Negative Breast CancerChina
-
Fudan UniversityRecruiting
-
Fudan UniversityRecruiting
Clinical Trials on ETBX-051
-
National Cancer Institute (NCI)CompletedHead and Neck Cancer | Head and Neck NeoplasmsUnited States
-
National Cancer Institute (NCI)CompletedProstatic Neoplasms | Prostatic CancerUnited States
-
National Cancer Institute (NCI)CompletedNeoplasms | Breast Cancer | Lung Cancer | Prostate Cancer | Colon CancerUnited States
-
CK Regeon Inc.Completed
-
ImmunityBio, Inc.Withdrawn
-
ENA Respiratory Pty LtdCompleted
-
Akros Pharma Inc.TerminatedSkin Diseases | Plaque PsoriasisUnited States, Canada
-
Akros Pharma Inc.CompletedRheumatoid ArthritisUkraine, United States, Argentina, Bulgaria, Romania, Peru, Russian Federation, Mexico, Colombia, Poland
-
ENA Respiratory Pty LtdWithdrawnCOVID-19 Pandemic
-
ImmunityBio, Inc.WithdrawnChordoma | Unresectable Malignant NeoplasmUnited States