Clinical Trials /

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

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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.
  • Official Title: 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.

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.067
  • NCT ID: NCT03387085

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
Aldoxorubicin HClNANT triple negative breast cancer (TNBC) Vaccine
ALT-803NANT triple negative breast cancer (TNBC) Vaccine
ETBX-011NANT triple negative breast cancer (TNBC) Vaccine
ETBX-051NANT triple negative breast cancer (TNBC) Vaccine
ETBX-061NANT triple negative breast cancer (TNBC) Vaccine
GI-4000NANT triple negative breast cancer (TNBC) Vaccine
GI-6207NANT triple negative breast cancer (TNBC) Vaccine
GI-6301NANT triple negative breast cancer (TNBC) Vaccine
haNK for InfusionNANT triple negative breast cancer (TNBC) Vaccine
avelumabNANT triple negative breast cancer (TNBC) Vaccine
bevacizumabNANT triple negative breast cancer (TNBC) Vaccine
CapecitabineNANT triple negative breast cancer (TNBC) Vaccine
CisplatinNANT triple negative breast cancer (TNBC) Vaccine
CyclophosphamideNANT triple negative breast cancer (TNBC) Vaccine
FluorouracilNANT triple negative breast cancer (TNBC) Vaccine
LeucovorinNANT triple negative breast cancer (TNBC) Vaccine
nab-PaclitaxelNANT triple negative breast cancer (TNBC) Vaccine
lovazaNANT triple negative breast cancer (TNBC) Vaccine

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
NANT triple negative breast cancer (TNBC) VaccineExperimentalA combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, SBRT.
  • Aldoxorubicin HCl
  • Capecitabine
  • Cisplatin
  • Cyclophosphamide
  • Fluorouracil
  • Leucovorin
  • nab-Paclitaxel
  • lovaza

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years old.

          2. Able to understand and provide a signed informed consent that fulfills the relevant
             IRB or Independent Ethics Committee (IEC) guidelines.

          3. Histologically-confirmed metastatic or unresectable TNBC that has either progressed on
             or after anthracycline-based chemotherapy 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.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          5. Have at least 1 measurable lesion of ≥ 1.5 cm.

          6. 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.

          7. Must be willing to provide blood samples prior to the start of treatment on this
             study.

          8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of
             treatment, if considered safe by the Investigator.

          9. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol.

         10. 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, autoimmune disease associated with lymphoma).

          3. History of organ transplant requiring immunosuppression.

          4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
             colitis).

          5. Inadequate organ function, evidenced by the following laboratory results:

               1. Absolute neutrophil count < 1000 cells/mm3.

               2. Platelet count < 75,000 cells/mm3.

               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 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. Subjects with
             uncontrolled hypertension should be medically managed on a stable regimen to control
             hypertension prior to study entry.

          7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection
             fraction (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 30 days prior to initiation of treatment on 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b primary endpoint

Secondary Outcome Measures

Measure:Objective response rate by RECIST
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Objective response rate by irRC
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Progression-free survival by RECIST during Phase 1b
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Progression-free survival by irRC during Phase 1b
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Overall survival
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Duration of response by RECIST and irRC
Time Frame:1 year
Safety Issue:
Description:Phase 1b secondary endpoint
Measure: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
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Patient-reported outcomes of pancreatic cancer symptoms
Time Frame:8 weeks
Safety Issue:
Description:Phase 1b secondary endpoint
Measure:Objective response rate by irRC
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Progression-free survival by RECIST during Phase 2
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Progression-free survival by irRC during Phase 2
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Overall survival
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Duration of response by RECIST and irRC
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure: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
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Patient-reported outcomes of pancreatic cancer symptoms
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint
Measure:Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NantKwest, Inc.

Last Updated

January 4, 2018