An Open-Label Randomized Phase 2 Trial Of The NANT NEOADJUVANT Triple-Negative Breast Cancer (TNBC) VACCINE VS Standard-Of-Care For The Neoadjuvant Treatment Of Subjects With TNBC

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



Sponsors

Lead Sponsor



Source

NantKwest, Inc.

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No


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).

Detailed Description

Treatment will be administered in 2 phases, a neoadjuvant phase and a postoperative phase.
The neoadjuvant phase will be 18 weeks for patients enrolled in the experimental arm and 16
weeks for those enrolled in the control arm.

Following the neoadjuvant phase, all subjects will undergo determination of their current
response status and appropriate breast surgery and node dissection after which assessment for
pCR will be conducted following completion of neoadjuvant systemic therapy. Pathologists
interpreting surgical specimens for pCR assessment will be blinded to the treatment arm.

All subjects, regardless of whether or not they have achieved a pCR, will then enter the
postoperative phase where they will receive adjuvant treatment. A small portion of the
corresponding neoadjuvant therapy, either nab-paclitaxel or paclitaxel, will be administered
as adjuvant treatment postoperatively. Adjuvant treatment will continue in the postoperative
phase until the subject experiences unacceptable toxicity (not correctable with dose
reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's
best interest to continue treatment.

Overall Status

Not yet recruiting

Start Date

2018-09-01

Completion Date

2021-12-01

Primary Completion Date

2020-06-01

Phase

Phase 2

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Pathological Complete Response Rate
8 months

Secondary Outcome

Measure

Time Frame

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

Enrollment

376

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Drug

Intervention Name


Description

albumin-binding prodrug of doxorubicin HCl

Arm Group Label

Group A


Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

Ad5 [E1-, E2b-]-CEA

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

Ad5 [E1-, E2b-]-Brachyury vaccine

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

CEA yeast vaccine

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

Brachyury yeast vaccine

Arm Group Label

Group A


Intervention Type

Drug

Intervention Name


Description

Avelumab

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Biological

Intervention Name


Description

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

Arm Group Label

Group A


Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Group A

Group B



Intervention Type

Drug

Intervention Name


Description

Doxorubicin HCL

Arm Group Label

Group B


Intervention Type

Drug

Intervention Name


Description

paclitaxel

Arm Group Label

Group B



Eligibility

Criteria

Inclusion Criteria:

1. Age ≥ 18 years.

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

3. 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.

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

5. Have at least 1 measurable lesion of ≥ 1.0 cm.

6. 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.

7. Must be willing to provide blood samples prior to the start of treatment on this study
for prospective tumor molecular profiling and exploratory analyses.

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

9. 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, and autoimmune disease associated with lymphoma).

3. History of organ transplant requiring immunosuppression.

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

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

1. Absolute neutrophil count (ANC) < 1,000 cells/mm^3.

2. Platelet count < 75,000 cells/mm^3.

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 (ALP) 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.

7. Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute 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 14 days prior to screening for 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.

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Contact

Last Name

NantKwest Clinical Review Team

Phone

800-988-6083

Email



Location

Facility

Chan Soon-Shiong Institute for Medicine
El Segundo California 90245 United States

Location Countries

Country

United States


Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor


Keyword


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Vaccines

Cyclophosphamide

Fluorouracil

Paclitaxel

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Doxorubicin



Arm Group

Arm Group Label

Group A

Arm Group Type

Experimental

Description

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


Arm Group Label

Group B

Arm Group Type

Active Comparator

Description

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



Firstreceived Results Date

N/A

Acronym

TNBC

Other Outcome

Measure

Quality of life by patient-reported outcomes

Time Frame

36 months

Description

Score on FACT-B QoL Assessment


Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Intervention Model Description

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.

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

May 25, 2018

Study First Submitted Qc

June 11, 2018

Study First Posted

June 12, 2018

Last Update Submitted

August 8, 2018

Last Update Submitted Qc

August 8, 2018

Last Update Posted

August 10, 2018


ClinicalTrials.gov processed this data on August 27, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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