QUILT-3.049: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy

NCT03175666 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: QUILT-3.049
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with metastatic or unresectable TNBC who have progressed on or after anthracycline-based chemotherapy or who have refused anthracycline-based chemotherapy.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

  Phase 1b primary endpoint (safety)

  1 year

• Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Phase 2 primary endpoint (ORR by RECIST)

  1 year

• ORR by Immune-related response criteria (irRC )

  Phase 2 primary endpoint (ORR by irRC)

  1 year

Secondary Outcomes (9)

• ORR by RECIST Version 1.1

  1 year

• ORR by irRC

  1 year

• Progression-free survival (PFS) by RECIST Version 1.1

  2 years

• PFS by irRC

  2 years

• Overall survival (OS): time from the date of first treatment to the date of death (any cause)

  2 years

Study Arms (1)

Nant TNBC

EXPERIMENTAL

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

Biological: avelumab; Biological: bevacizumab; Drug: capecitabine; Drug: cisplatin; Drug: cyclophosphamide; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-paclitaxel; Drug: Lovaza; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-011; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Biological: haNK

Interventions

avelumab BIOLOGICAL

Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Nant TNBC

bevacizumab BIOLOGICAL

Recombinant human anti-VEGF IgG1 monoclonal antibody

Nant TNBC

capecitabine DRUG

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

Nant TNBC

cisplatin DRUG

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

Nant TNBC

cyclophosphamide DRUG

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

Nant TNBC

5-Fluorouracil DRUG

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

Nant TNBC

Leucovorin 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)

Nant TNBC

nab-paclitaxel 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

Nant TNBC

Lovaza DRUG

omega-3-acid ethyl esters)

Nant TNBC

Stereotactic Body Radiation Therapy RADIATION

(SBRT)

Nant TNBC

ALT-803 BIOLOGICAL

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

Nant TNBC

ETBX-011 BIOLOGICAL

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

Nant TNBC

ETBX-051 BIOLOGICAL

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

Nant TNBC

ETBX-061 BIOLOGICAL

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

Nant TNBC

GI-4000 BIOLOGICAL

RAS yeast vaccine

Nant TNBC

GI-6207 BIOLOGICAL

CEA yeast vaccine

Nant TNBC

GI-6301 BIOLOGICAL

Brachyury yeast vaccine

Nant TNBC

haNK BIOLOGICAL

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

Nant TNBC

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 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Histologically confirmed metastatic or unresectable TNBC that has either progressed on or after anthracycline-based chemotherapy or subject has refused anthracycline-based chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have at least 1 measurable lesion of ≥ 1.5 cm.
• Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anticancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
• 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.
• 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.

You may not qualify if:

• History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
• Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; 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.
• 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).
• Requires whole blood transfusion to meet eligibility criteria.
• Inadequate organ function, evidenced by the following laboratory results:
• White blood cell (WBC) count \< 3,500 cells/mm3.
• Absolute neutrophil count \< 1,500 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Hemoglobin \< 9 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).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

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

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; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

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: May 31, 2017
• First Posted: June 5, 2017
• Study Start: December 1, 2017
• Primary Completion: January 1, 2019
• Study Completion: December 28, 2021
• Last Updated: February 21, 2025

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share