Clinical trial NCT03387085
Conditions: Triple Negative Breast Cancer
Sponsor: ImmunityBio, Inc.
Start date: 2018-03-19; Completion date: 2024-01-16
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

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.

Arms: arm 1: 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.
Interventions: intervention 1: Aldoxorubicin HCl intervention 2: N-803 intervention 3: ETBX-011 intervention 4: ETBX-051 intervention 5: ETBX-061 intervention 6: GI-4000 intervention 7: GI-6207 intervention 8: GI-6301 intervention 9: haNK for Infusion intervention 10: avelumab intervention 11: bevacizumab intervention 12: Capecitabine intervention 13: Cisplatin intervention 14: Cyclophosphamide intervention 15: 5-Fluorouracil intervention 16: Leucovorin intervention 17: nab-Paclitaxel intervention 18: SBRT
Intervention descriptions: intervention 1: Aldoxorubicin hydrochloride intervention 2: Recombinant human super agonist interleukin-15 (IL-15) complex intervention 3: Ad5 \[E1-, E2b-\]-CEA intervention 4: Ad5 \[E1-, E2b-\]-Brachyury vaccine intervention 5: Ad5 \[E1-, E2b-\]-MUC1 intervention 6: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins intervention 7: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins intervention 8: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins intervention 9: NK-92 \[CD16.158V, ER IL-2\] intervention 10: Recombinant human anti-PD-L1 IgG1 monoclonal antibody intervention 11: Recombinant human anti-VEGF IgG1 monoclonal intervention 12: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine intervention 13: cis-diamminedichloroplatinum(II) intervention 14: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate intervention 15: 5-fluoro-2,4 (1H,3H)-pyrimidinedione intervention 16: 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 intervention 17: 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 intervention 18: Stereotactic Body Radiation Therapy

Protocol documents:
Prot_SAP_000.pdf: 
NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
NANT TRIPLE NEGATIVE BREAST CANCER (TNBC) 
VACCINE: MOLECULARLY INFORMED 
INTEGRATED IMMUNOTHERAPY COMBINING 
INNATE HIGH-AFFINITY NATURAL KILLER (haNK) 
CELL THERAPY WITH ADAPTIVE T-CELL THERAPY 
(ADENOVIRUS, YEAST, FUSION PROTEIN VACCINE) 
IN SUBJECTS WITH TNBC WHO HAVE PROGRESSED 
ON OR AFTER STANDARD-OF-CARE THERAPY 
 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
 
Protocol Version 
Date 
Version 1 
21 November 2017 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or Specialist Term 
Explanation 
Ad5 
Adenovirus serotype-5 
β-HCG 
β-Human chorionic gonadotropin 
ADCC 
Antibody-dependent cellular cytotoxicity 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
AST 
Aspartate aminotransferase 
BUN 
Blood urea nitrogen 
CAP 
College of American Pathologists 
CAR 
Chimeric antigen receptor 
CBC 
Complete blood count 
CEA 
Carcinoembryonic antigen 
CEP 
Circulating endothelial progenitor cell 
CLIA 
Clinical Laboratory Improvement Amendments 
CR 
Complete response 
CRF 
Case report form 
CSC 
Cancer stem cell 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAMP 
Damage-associated molecular pattern 
DCR 
Disease control rate 
DC 
Dendritic cell 
DFS 
Disease-free survival 
DLT 
Dose-limiting toxicity 
DOR 
Duration of response 
DSMB 
Independent Drug Safety Monitoring Board 
DTH 
Delayed-type hypersensitivity 
EBV 
Epstein-Barr Virus 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Abbreviation or Specialist Term 
Explanation 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EGF 
Epidermal growth factor 
ELISA 
Enzyme-linked immunosorbent assay 
EOS 
End of study 
EOT 
End of treatment 
ER 
Estrogen receptor 
FACT-B 
Functional Assessment of Cancer Therapy-Breast 
Cancer 
FFPE 
Formalin-fixed paraffin-embedded 
FOLFIRINOX 
Folinic acid (leucovorin), 5-FU, irinotecan, and 
oxaliplatin 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GTV 
Gross tumor volume 
GvHD 
Graft versus host disease 
HER2 
Human Epidermal Growth Factor Receptor 2 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HSA 
Human serum albumin 
HSCT 
Hematopoietic stem cell transplant 
HTD 
Highest tested dose 
ICD 
Immunological cell death 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IHC 
Immunohistochemistry 
IL 
Interleukin 
IMRT 
Intensity-modulated radiation therapy 
IP 
Investigational product 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Abbreviation or Specialist Term 
Explanation 
IRB 
Institutional Review Board 
irCR 
Immune-related complete response 
irPD 
Immune-related progressive disease 
irPR 
Immune-related partial response 
irRC 
Immune-related response criteria 
irSD 
Immune-related stable disease 
IV 
Intravenous 
KIR 
Killer cell immunoglobulin-like receptor 
LDH 
Lactate dehydrogenase 
LDMC 
Low-dose, metronomic cytotoxic chemotherapy 
LLD 
Longest lesion diameter 
LLN 
Lower limit of normal 
LVEF 
Left ventricular ejection fraction 
M2 cells 
M2 macrophages 
MCB 
Master cell bank 
MCC 
Merkel cell carcinoma 
mCRC 
Metastatic colorectal cancer 
MDSC 
Myeloid-derived suppressor cell 
MedRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major histocompatibility complex 
MIP 
Macrophage inflammatory protein 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
MUC1 
Mucin 1 
MV 
Megavolt 
NANT 
Neoantigen, Adenovirus, NK Cell, T cell: delivery of 
combined immune oncology multi-modality treatment 
NCI 
National Cancer Institute 
NK 
Natural killer (cell) 
NOD/SCID 
Non-obese diabetic severe combined 
immunodeficiency 
NSAID 
Nonsteroidal anti-inflammatory drug 
NSCLC 
Non-small cell lung cancer 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Abbreviation or Specialist Term 
Explanation 
NSG 
Non-obese diabetic scid gamma 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PD 
Progressive disease 
PD-1 
Programmed cell death protein 1 
PD-L1 
Programmed death-ligand 1 
PFS 
Progression-free survival 
PI 
Principal Investigator 
PR 
Partial response 
PRO 
Patient-reported outcome 
qPCR 
Quantitative polymerase chain reaction 
RCC 
Renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SBRT 
Stereotactic body radiotherapy 
SC 
Subcutaneous 
SCC 
Squamous cell carcinoma 
SCID 
Severe combined immunodeficiency 
SD 
Stable disease 
SoC 
Standard of Care 
SOP 
Standard operating procedure 
SRC 
Safety Review Committee 
SUSAR 
Suspected unexpected serious adverse reaction 
TAA 
Tumor-associated antigen 
TAM 
Tumor-associated macrophage 
TME 
Tumor microenvironment 
TNF 
Tumor necrosis factor 
Treg 
Regulatory T cells 
ULN 
Upper limit of normal 
US 
United States 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Abbreviation or Specialist Term 
Explanation 
VEGF 
Vascular endothelial growth factor 
VP 
Viral particles 
WBC 
White blood cell 
YU 
Yeast unit 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human super agonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA [carcinoembryonic antigen] 
vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (RAS yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine) 
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for IV use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Omega-3-acid ethyl esters (LOVAZA® Capsules, for oral use) 
19. Stereotactic Body Radiation Therapy (SBRT) 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-Brachyury  
5. Ad5 [E1-, E2b-]-MUC1 
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
7. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast based vaccine expressing the human Brachyury oncoprotein 
9. NK92 [CD16.158V, ER IL2] cells 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Omega-3-acid ethyl esters 
19. Radiation 
Title of Study:  
NANT triple negative breast cancer (TNBC) vaccine: molecularly informed integrated 
immunotherapy combining innate high-affinity natural killer (haNK) cell therapy with adaptive T-cell 
therapy (adenovirus, yeast, fusion protein vaccine) in subjects with TNBC who have progressed on or 
after standard-of-care therapy. 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Study Number: 
QUILT-3.067 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC 
vaccine regimen in subjects with TNBC who have progressed on or after standard-of-care 
(SoC) therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective 
response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of 
response (DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported 
outcomes (PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses, and 
molecular changes in circulating tumor DNA (ctDNA) and RNA (ctRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen 
as assessed by ORR. 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
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. 
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
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 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), 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) of 
target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1 and immune-related response criteria (irRC). 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood 
(subject-matched normal comparator against the tumor tissue) collected prior to treatment on this 
study. Treatment with all study drugs except GI-4000 may be initiated before FFPE tumor tissue 
and/or results from prospective tumor molecular profiling are available; in the event that this occurs, 
treatment of subjects with tumors positive for specific RAS mutations targeted by GI-4000 will begin 
as soon as molecular profiling results are available. More information on the collection of tumor 
tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples for 
the exploratory tumor molecular profiling. 
Subjects will receive GI-4000 if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. As described in Section 1.5.12, GI-4000 is 4 separate products from the 
GI-4000 series (GI-4014, GI-4015, GI- 4016, and GI-4020); each of these expresses a combination of 
mutated RAS oncoproteins. The specific RAS mutation will determine which GI-4000 product will be 
used for treatment (GI-4014 for G12V, GI-4015 for G12C, GI-4016 for G12D, GI-4020 for G12R or 
Q61H, and GI-4014, GI-4015, or GI-4016 for Q61L or Q61R). 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cisplatin, 
cyclophosphamide, Ad5-based vaccines (ETBX-011, ETBX-051, and ETBX-061), 5-FU/leucovorin, 
yeast-based vaccines (GI-4000, GI-6207, GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid 
ethyl esters will be repeated every 3 weeks. Concurrent SBRT will be given during the first two 
3-week cycles. Radiation will be administered to no more than 5 tumor sites using SBRT, as 
described in Section 5.1.5.1. 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily: 
• 
Omega-3-acid ethyl esters (by mouth [PO] twice a day [BID] [3 × 1 g capsules and 
2 × 1 g capsules]) 
 
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NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 
 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV)  
Days 1 and 15, every 3 weeks:  
• 
Leucovorin (20 mg/m2 IV bolus) 
Days 1–5 and 15–19, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours)   
Days 1–5, 8–12, and 15-19 every 3 weeks:  
• 
Cyclophosphamide (50 mg PO BID) 
Days 1 and 8, every 3 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV)  
Day 5 (every 3 weeks for 3 cycles then every 8 weeks thereafter):   
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 virus particles [VP]/vaccine/dose 
subcutaneously [SC]) 
Days 8 and 15 (every 3 weeks): 
• 
Aldoxorubicin HCl (80 mg/m2 IV on day 8; 30 mg/m2 IV on day 15) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
Days 9 and 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC 30 minutes prior to haNK infusion) 
Days 9, 11, 16, and 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 8 weeks thereafter:  
• 
GI-4000, GI-6207, and GI-6301 (40 yeast units [YU]/vaccine/dose SC)  
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
 
 
 
 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles. The treatment 
regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cyclophosphamide, capecitabine, 
Ad5-based vaccines (ETBX-011, ETBX-051, and ETBX-061), yeast-based vaccines (GI-4000, 
GI-6207, and GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated 
every 2 weeks. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (PO BID [3 × 1 g capsules and 2 × 1 g capsules]) 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (50 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC, 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5, every 8 weeks thereafter: 
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 VP/vaccine/dose SC) 
• 
GI-4000, GI-6207, GI-6301 (40 YU/vaccine/dose SC), 2 hours after administration of the 
Ad5-based vaccines 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1 and irRC. 
• 
PFS by RECIST Version 1.1 and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months). 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1 and irRC.  
Secondary Endpoints: 
• 
PFS by RECIST Version 1.1 and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months). 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 
4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
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NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 
 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. In the phase 2 portion of the 
study, 19 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the study 
proceeds to the second stage of Simon’s two-stage optimal design, an additional 36 subjects will be 
enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
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 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, 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. 
 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
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: 
a. Absolute neutrophil count < 750 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Total bilirubin greater than twice the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
d. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
e. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
f. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
g. 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. To control hypertension, it is recommended to first start 
propranolol SR 80 mg daily prior to initiating other hypertensive medications. 
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. 
 
 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
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 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. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  or 30 mg/m2 
(induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
1 × 1011 VP/dose  
SC 
ETBX-051 
1 × 1011 VP/dose  
SC 
ETBX-061 
1 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
GI-6207 
40 YU/dose 
SC 
GI-6301 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2  
PO BID 
Cisplatin 
40 mg/m2 
IV 
Cyclophosphamide  
50 mg 
PO BID 
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Approved Products 
Dosage 
Mode of Administration 
Nab-paclitaxel  
125 mg (induction); 
100 mg (maintenance) 
IV 
Omega-3-acid ethyl esters 
5 g 
PO 
SBRT 
8 Gy maximum (exact dose to 
be determined by the radiation 
oncologist) 
External beam radiation 
Duration of Treatment: 
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum). 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they 
experience progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will 
be conducted to determine the absolute amounts of specific proteins, to confirm expression of genes 
that are correlative of disease progression and/or response, and to determine the cutoff values for 
response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated 
by standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Figure 1: 
Study Treatment Schema 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Figure 2: 
Induction Phase Treatment Schema 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 
 
Figure 3: 
Maintenance Phase Treatment Schema 
 
Confidential and Proprietary 
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NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
Confidential and Proprietary 
1 
TITLE PAGE 
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 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
Protocol Version 
Date 
Version 1 
21 November 2017 
Version 2 
27 December 2017 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
2 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human super agonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA [carcinoembryonic antigen] 
vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (RAS yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine) 
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Omega-3-acid ethyl esters (LOVAZA® Capsules, for oral use) 
19. Stereotactic Body Radiation Therapy (SBRT) 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
4 
Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-Brachyury  
5. Ad5 [E1-, E2b-]-MUC1 
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
7. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast based vaccine expressing the human Brachyury oncoprotein 
9. NK92 [CD16.158V, ER IL2] cells 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Omega-3-acid ethyl esters 
19. Radiation 
Title of Study:  
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. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
5 
Study Number: 
QUILT-3.067 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC 
vaccine regimen in subjects with TNBC who have progressed on or after standard-of-care 
(SoC) therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective 
response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of 
response (DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported 
outcomes (PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses, and 
molecular changes in circulating tumor DNA (ctDNA) and RNA (ctRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen 
as assessed by ORR using RECIST Version 1.1. 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
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. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. Preliminary 
assessment of the safety of the treatment regimen will occur by the NantKwest Safety Review 
Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
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 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
6 
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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography-computed tomography 
(PET-CT) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid 
Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC). 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood 
(subject-matched normal comparator against the tumor tissue) collected prior to treatment on this 
study. Treatment with all study drugs except GI-4000 may be initiated before FFPE tumor tissue 
and/or results from prospective tumor molecular profiling are available; in the event that this occurs, 
treatment of subjects with tumors positive for specific RAS mutations targeted by GI-4000 will begin 
as soon as molecular profiling results are available. More information on the collection of tumor 
tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples for 
the exploratory tumor molecular profiling. 
Subjects will receive GI-4000 if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. As described in Section 1.5.12, GI-4000 is 4 separate products from the 
GI-4000 series (GI-4014, GI-4015, GI- 4016, and GI-4020); each of these expresses a combination of 
mutated RAS oncoproteins. The specific RAS mutation will determine which GI-4000 product will be 
used for treatment (GI-4014 for G12V, GI-4015 for G12C, GI-4016 for G12D, GI-4020 for G12R or 
Q61H, and GI-4014, GI-4015, or GI-4016 for Q61L or Q61R). 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cisplatin, 
cyclophosphamide, Ad5-based vaccines (ETBX-011, ETBX-051, and ETBX-061), 5-FU/leucovorin, 
yeast-based vaccines (GI-4000, GI-6207, GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid 
ethyl esters will be repeated every 3 weeks. Concurrent SBRT will be given during the first two 
3-week cycles. Radiation will be administered to no more than 5 tumor sites using SBRT, as 
described in Section 5.1.5.1. 
 
 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
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The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily: 
• 
Omega-3-acid ethyl esters (2 g by mouth [PO] twice a day [BID]) 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV)  
Days 1 and 15, every 3 weeks:  
• 
Leucovorin (20 mg/m2 IV bolus) 
Days 1–5 and 15–19, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours)   
Days 1–5, 8–12, and 15-19 every 3 weeks:  
• 
Cyclophosphamide (25 mg PO BID) 
Days 1 and 8, every 3 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV over 1 hour)  
Day 5, every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 virus particles [VP]/vaccine/dose 
subcutaneously [SC]) 
Days 8 and 15, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV on day 8; 30 mg/m2 IV on day 15) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
Days 9 and 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
Days 9, 11, 16, and 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter:  
• 
GI-4000, GI-6207, and GI-6301 (40 yeast units [YU]/vaccine/dose SC)  
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
8 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles. The treatment 
regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cyclophosphamide, capecitabine, 
Ad5-based vaccines (ETBX-011, ETBX-051, and ETBX-061), yeast-based vaccines (GI-4000, 
GI-6207, and GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated 
every 2 weeks. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (2 g PO BID) 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC, at least 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5, every 8 weeks thereafter: 
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 VP/vaccine/dose SC) 
• 
GI-4000, GI-6207, GI-6301 (40 YU/vaccine/dose SC), 2 hours after administration of the 
Ad5-based vaccines 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
Confidential and Proprietary 
9 
Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 
and irRC. 
• 
QoL by PROs. 
 


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Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE 
Version 4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 19 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 36 subjects 
will be enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
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 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 


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Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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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: 
a. Absolute neutrophil count < 1000 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. 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. 


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Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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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. 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  or 30 mg/m2 
(induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
1 × 1011 VP/dose  
SC 
ETBX-051 
1 × 1011 VP/dose  
SC 
ETBX-061 
1 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
GI-6207 
40 YU/dose 
SC 
GI-6301 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2  
PO BID 
Cisplatin 
40 mg/m2 
IV 
Cyclophosphamide  
25 mg 
PO BID 
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Approved Products 
Dosage 
Mode of Administration 
Nab-paclitaxel  
125 mg (induction); 
100 mg (maintenance) 
IV 
Omega-3-acid ethyl esters 
2 g 
PO BID 
SBRT 
8 Gy maximum (exact dose to 
be determined by the radiation 
oncologist) 
External beam radiation 
Duration of Treatment: 
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum). 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they 
experience progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will 
be conducted to determine the absolute amounts of specific proteins, to confirm expression of genes 
that are correlative of disease progression and/or response, and to determine the cutoff values for 
response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated 
by standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Figure 1: 
Study Treatment Schema 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Figure 2: 
Induction Phase Treatment Schema 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
 
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Figure 3: 
Maintenance Phase Treatment Schema 
 


NANT TNBC Vaccine 
NantK west, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 1 
APPENDIX 1. SPONSOR SIGNATURE 
Study 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 theranv. 
Study Number: 
QUILT-3.067 
Version Number: 
2 
Final Date: 
27 December 2017 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
Signed: 
. Lee, MD 
S nior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-6391 
Confidential and Proprietary 
158 
Date: / )-)._?-/-=/-


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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TITLE PAGE 
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 
 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
 
Protocol Version 
Date 
Version 1 
21 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human superagonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (RAS yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine) 
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Stereotactic Body Radiation Therapy (SBRT) 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-Brachyury  
5. Ad5 [E1-, E2b-]-MUC1 
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
7. Recombinant yeast-based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast-based vaccine expressing the human Brachyury oncoprotein 
9. NK-92 [CD16.158V, ER IL2] cells 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Radiation 
Title of Study:  
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. 
Study Number: 
QUILT-3.067 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC 
vaccine regimen in subjects with TNBC who have progressed on or after standard-of-care 
(SoC) therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective 
response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of 
response (DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported 
outcomes (PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses, and 
molecular changes in circulating tumor DNA (ctDNA) and RNA (ctRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen 
as assessed by ORR using RECIST Version 1.1 based on Blinded Independent Central 
Review (BICR). 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
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. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. Preliminary 
assessment of the safety of the treatment regimen will occur by the NantKwest Safety Review 
Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
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 


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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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography-computed tomography 
(PET-CT) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid 
Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC). In order to document 
PD, unscheduled tumor assessments may be done if the Investigator observes any signs and 
symptoms of PD.  For responding subjects (PR or CR), a confirmatory response assessment should be 
done at 4 weeks after the initial response. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on formalin-fixed, paraffin-embedded 
(FFPE) tumor tissue and whole blood (subject-matched normal comparator against the tumor tissue) 
collected prior to treatment on this study, as described in Section 3.1.1. More information on the 
collection of tumor tissue and whole blood is described in Section 6.4.1.2 and is similar to the 
collection of samples for the exploratory tumor molecular profiling. 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
Concurrent SBRT will be given during the first two 3-week cycles. Radiation will be administered to 
no more than 5 tumor sites using SBRT, as described in Section 5.1.5.1. 
 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV)  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV over 1 hour) 
Days 1–5, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours)   
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 


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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 virus particles [VP]/vaccine/dose 
subcutaneously [SC]) 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV over 30 minutes) 
• 
Cisplatin (20 mg/m2 IV over 1 hour)  
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Days 8–12, every 3 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter:  
• 
GI-4000, GI-6207, and GI-6301 (40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Day 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV)  
Day 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV) 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles.  
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
 


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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC, at least 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
ETBX-011, ETBX-051, ETBX-061 (1 × 1011 VP/vaccine/dose SC) 
• 
GI-4000, GI-6207, GI-6301 (40 YU/vaccine/dose SC), 2 hours after administration of the 
Ad5-based vaccines 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 
and irRC. 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE 
Version 4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by the Investigator; in the phase 2 
portion of the study, the primary assessment of response will be based on BICR. A charter for the 
conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 23 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 32 subjects 
will be enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
 
 


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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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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 ≥ 1.0 cm. 
6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent 
anticancer treatment 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, 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.   


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Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).   
5. Inadequate organ function, evidenced by the following laboratory results: 
a. Absolute neutrophil count (ANC) < 1,000 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. 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. 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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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. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
1 × 1011 VP/dose  
SC 
ETBX-051 
1 × 1011 VP/dose  
SC 
ETBX-061 
1 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
GI-6207 
40 YU/dose 
SC 
GI-6301 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID 
PO 
Cisplatin 
40 mg/m2 (day 1);  
20 mg/m2 (day 8) 
IV 
Cyclophosphamide  
25 mg BID (days 1–5, induction) 
25 mg daily (days 8–12, induction) 
25 mg BID (maintenance) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (induction); 
100 mg (maintenance) 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation 
oncologist) 
 
 
External beam radiation 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Duration of Treatment: 
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum). 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they 
experience progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. In order to document PD, unscheduled tumor 
assessments may be done if the Investigator observes any signs and symptoms of PD. For responding 
subjects (PR or CR), a confirmatory response assessment should be done at 4 weeks after the initial 
response. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
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Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will 
be conducted to determine the absolute amounts of specific proteins, to confirm expression of genes 
that are correlative of disease progression and/or response, and to determine the cutoff values for 
response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated 
by standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Figure 1: 
Study Treatment Schema 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Figure 2: 
Induction Phase Treatment Schema 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
 
Confidential and Proprietary 
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Figure 3: 
Maintenance Phase Treatment Schema 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 2 
APPENDIX 1. SPONSOR SIGNATURE 
Study 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. 
Study Number: 
QUILT-3.067 
Version Number: 
3 
Final Date: 
01March2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
Sign00.: _,,/
7-:d 
Date: /14,{lv(f? / }cJ/8 
JohJYif Lee, MD 
Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone:+ 1-605-610-6391 
Confidential and Proprietary 
155 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
Confidential and Proprietary 
1 
TITLE PAGE 
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 
 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
 
Protocol Version 
Date 
Version 1 
21 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
02 July 2018 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
Confidential and Proprietary 
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STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
Confidential and Proprietary 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human superagonist interleukin-15 (IL-15) complex [also known as IL-
15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (RAS yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine) 
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide Tablets, 
USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Stereotactic Body Radiation Therapy (SBRT) 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
Confidential and Proprietary 
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Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as IL-
15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-Brachyury  
5. Ad5 [E1-, E2b-]-MUC1 
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
7. Recombinant yeast-based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast-based vaccine expressing the human Brachyury oncoprotein 
9. NK-92 [CD16.158V, ER IL2] cells 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Radiation 
Title of Study: 
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. 
Study Number: 
QUILT-3.067 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
Confidential and Proprietary 
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Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC vaccine 
regimen in subjects with TNBC who have progressed on or after standard-of-care (SoC) 
therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective response 
rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response 
(DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported outcomes 
(PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses, and 
molecular changes in circulating tumor DNA (ctDNA) and RNA (ctRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen as 
assessed by ORR using RECIST Version 1.1 based on Blinded Independent Central 
Review (BICR). 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
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. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. Preliminary 
assessment of the safety of the treatment regimen will occur by the NantKwest Safety Review 
Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 3 subjects 
suggest that the combination therapy is tolerable. 
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 confirmed 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. 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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Treatment will continue in the maintenance phase until the subject experiences confirmed 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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or 
magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related response criteria 
(irRC). In order to document PD, unscheduled tumor assessments may be done if the Investigator 
observes any signs and symptoms of PD. Experimental treatment may continue and an imaging 
assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4–6 weeks 
after the initial response. Subjects who withdraw from the study for reasons other than progression are 
encouraged not to initiate another anticancer treatment unless/until progression has been documented at 
a follow-up visit. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on formalin-fixed, paraffin-embedded (FFPE) 
tumor tissue and whole blood (subject-matched normal comparator against the tumor tissue) collected 
prior to treatment on this study, as described in Section 3.1.1. More information on the collection of 
tumor tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples 
for the exploratory tumor molecular profiling. 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
Concurrent SBRT will be given during the first two 3-week cycles. Radiation will be administered to 
no more than 5 tumor sites using SBRT, as described in Section 5.1.5.1. 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV), for the first 2 cycles only  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV) 


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Days 1–5, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) (1 × 
1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV) 
• 
Cisplatin (20 mg/m2 IV)  
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for the 
first 2 cycles only) 
Days 8–12, every 3 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV) 
• 
ALT-803 (15 μg/kg SC) 
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter: 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (MUC1) (40 yeast 
units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Day 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for the 
first 2 cycles only) 
Day 16, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV) 
 
 


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Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID, up to a maximum of 1,000 mg per dose) 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (15 µg/kg SC) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) (1 × 
1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), GI-6301 (Brachyury) 
(40 YU/vaccine/dose SC), 2 hours after administration of the Ad5-based vaccines 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
Days 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 


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Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 and 
irRC. 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03. 


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Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter for 
the conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 23 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 32 subjects will 
be enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
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 ≥ 1.0 cm. 
6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent 
anticancer treatment 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 


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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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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: 
a. Absolute neutrophil count (ANC) < 1,000 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or 
>10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. 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. 


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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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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. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
15 µg/kg  
SC 
ETBX-011 (CEA) 
1 × 1011 VP/dose  
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose  
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose  
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID, up to a maximum 
of 1,000 mg per dose 
PO 
Cisplatin 
40 mg/m2 (day 1);  
20 mg/m2 (day 8) 
IV 


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Cyclophosphamide  
25 mg BID (days 1–5) 
25 mg daily (days 8–12) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (induction); 
100 mg (maintenance) 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation 
oncologist) 
External beam radiation 
Duration of Treatment: 
• 
Induction phase: Up to 1 year. 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they experience 
progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw consent, or if 
the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed for: 
• 
CT or MRI scan assessment (see Section 6.1.2) 
• 
Collection of vital status every 90 days (± 14 days) 
Subjects should be followed until either death (any cause) or for a minimum of 24 months past 
administration of the first dose of study drug.  
Following documented PD, subjects may continue to be followed by the investigational physician or a 
third party by phone or review of medical records until withdrawal of consent, lost to follow-up, or 
death (by any cause). Additional information from a subject’s medical records relevant to this study 
may be provided to NantKwest as needed to understand the safety and efficacy of the regimen tested in 
this protocol. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 


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Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time of their first study 
treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in accordance 
with RECIST Version 1.1 and irRC. In order to document PD, unscheduled tumor assessments may be 
done if the Investigator observes any signs and symptoms of PD. Experimental treatment may continue 
and an imaging assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4-6 weeks 
after the initial response. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will be 
conducted to determine the absolute amounts of specific proteins, to confirm expression of genes that 
are correlative of disease progression and/or response, and to determine the cutoff values for response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject outcomes 
will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole blood. 
Expression levels of specific tumor- and immune-related analytes will be assessed by quantitative real-
time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA sequencing) and 
analyzed for correlations with subject outcomes. 
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 


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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


NANT TNBC Vaccine 
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Figure 1: 
Study Treatment Schema 
 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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Figure 2: 
Induction Phase Treatment Schema 
 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 3 
 
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Figure 3: 
Maintenance Phase Treatment Schema 
 
 




NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 4 
 
Confidential and Proprietary 
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TITLE PAGE 
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 
 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
 
Protocol Version 
Date 
Version 1 
21 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
02 July 2018 
Version 5 
01 August 2018 


NANT TNBC Vaccine 
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STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human superagonist interleukin-15 (IL-15) complex [also known as IL-
15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (RAS yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine) 
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide Tablets, 
USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Stereotactic Body Radiation Therapy (SBRT) 


NANT TNBC Vaccine 
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Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-Brachyury  
5. Ad5 [E1-, E2b-]-MUC1 
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
7. Recombinant yeast-based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast-based vaccine expressing the human Brachyury oncoprotein 
9. NK-92 [CD16.158V, ER IL2] cells 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Radiation 
Title of Study: 
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. 
Study Number: 
QUILT-3.067 


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Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC vaccine 
regimen in subjects with TNBC who have progressed on or after standard-of-care (SoC) 
therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective response 
rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response 
(DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported outcomes 
(PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses, and 
molecular changes in circulating tumor DNA (ctDNA) and RNA (ctRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen as 
assessed by ORR using RECIST Version 1.1 based on Blinded Independent Central 
Review (BICR). 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
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. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. Preliminary 
assessment of the safety of the treatment regimen will occur by the NantKwest Safety Review 
Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 3 subjects 
suggest that the combination therapy is tolerable. 
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 confirmed 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. 


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Treatment will continue in the maintenance phase until the subject experiences confirmed 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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or 
magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related response criteria 
(irRC). In order to document PD, unscheduled tumor assessments may be done if the Investigator 
observes any signs and symptoms of PD. Experimental treatment may continue and an imaging 
assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4–6 weeks 
after the initial response. Subjects who withdraw from the study for reasons other than progression are 
encouraged not to initiate another anticancer treatment unless/until progression has been documented at 
a follow-up visit. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on formalin-fixed, paraffin-embedded (FFPE) 
tumor tissue and whole blood (subject-matched normal comparator against the tumor tissue) collected 
prior to treatment on this study, as described in Section 3.1.1. More information on the collection of 
tumor tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples 
for the exploratory tumor molecular profiling. 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year.  
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV), for the first 2 cycles only  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (32 mg/m2 IV) 
Days 1–5, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 


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• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) 
(1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC])  
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury) 
(40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (100 mg/m2 IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for up 
to 4 cycles) 
Days 8–12, every 3 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
ALT-803 (15 μg/kg SC) 
• 
Avelumab (10 mg/kg IV) 
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 15, every 3 weeks: 
• 
Nab-paclitaxel (100 mg IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for up 
to 4 cycles) 
Day 16, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Nab-paclitaxel (100 mg IV) 


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Days 1–5, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Days 1, 3, and 5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID, up to a maximum of 1,000 mg per dose) 
Day 2, every 2 weeks:  
• 
ALT-803 (15 µg/kg SC) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) 
(1 × 1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), GI-6301 (Brachyury) 
(40 YU/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
Days 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
 


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Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 and 
irRC. 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter for 
the conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 23 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 32 subjects will 
be enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
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 


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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 ≥ 1.0 cm. 
6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent 
anticancer treatment 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, 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: 
a. Absolute neutrophil count (ANC) < 1,000 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 


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documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or 
>10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. 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. 


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Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
100 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
15 µg/kg  
SC 
ETBX-011 (CEA) 
1 × 1011 VP/dose  
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose  
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose  
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID, up to a maximum 
of 1,000 mg per dose 
PO 
Cisplatin 
32 mg/m2  
IV 
Cyclophosphamide  
25 mg BID (days 1–5) 
25 mg daily (days 8–12) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (day 1 of induction); 
100 mg (day 15 of induction and 
day 1 of maintenance) 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation 
oncologist) 
External beam radiation 
Duration of Treatment: 
• 
Induction phase: Up to 1 year. 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they experience 
progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw consent, or if 
the Investigator feels it is no longer in their best interest to continue treatment. 


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Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed for: 
• 
CT or MRI scan assessment (see Section 6.1.2) 
• 
Collection of vital status every 90 days (± 14 days) 
Subjects should be followed until either death (any cause) or for a minimum of 24 months past 
administration of the first dose of study drug.  
Following documented PD, subjects may continue to be followed by the investigational physician or a 
third party by phone or review of medical records until withdrawal of consent, lost to follow-up, or 
death (by any cause). Additional information from a subject’s medical records relevant to this study 
may be provided to NantKwest as needed to understand the safety and efficacy of the regimen tested in 
this protocol. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time of their first study 
treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in accordance 
with RECIST Version 1.1 and irRC. In order to document PD, unscheduled tumor assessments may be 
done if the Investigator observes any signs and symptoms of PD. Experimental treatment may continue 
and an imaging assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4-6 weeks 
after the initial response. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will be 
conducted to determine the absolute amounts of specific proteins, to confirm expression of genes that 
are correlative of disease progression and/or response, and to determine the cutoff values for response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject outcomes 
will be assessed. 
 


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ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole blood. 
Expression levels of specific tumor- and immune-related analytes will be assessed by quantitative real-
time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA sequencing) and 
analyzed for correlations with subject outcomes. 
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


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Figure 1: 
Study Treatment Schema 
 


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Figure 2: 
Induction Phase Treatment Schema 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 
 


NANT TNBC Vaccine 
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Clinical Trial Protocol: QUILT-3.067 Amendment 4 
APPENDIX 2. SPONSOR SIGNATURE 
Study 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. 
Study Number: 
QUILT-3.067 
Version Number: 
5 
Final Date: 
01August2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
Signe 
H.Lee,MD 
enior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone:+ 1-605-610-6391 
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156 
Date: g-/-XJ0 


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TITLE PAGE 
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 
 
Study Number: 
QUILT-3.067 
IND Sponsor: 
NantKwest, Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Sponsor Contact:  
(For medical questions/emergencies) 
John H. Lee, MD 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
 
Protocol Version 
Date 
Version 1 
21 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
02 July 2018 
Version 5 
01 August 2018 
Version 6 
25 March 2019 


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STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6(R2)) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] 
vaccine) 
3. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
4. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
5. GI-4000 (RAS yeast vaccine) 
6. GI-6207 (CEA yeast vaccine) 
7. GI-6301 (Brachyury yeast vaccine) 
8. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion)  
9. N-803 (also known as ALT-803; recombinant human superagonist interleukin [IL]-15 complex 
[also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]) 
Name of Approved Products: 
10. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
11. Bevacizumab (AVASTIN® solution for IV infusion) 
12. Capecitabine (XELODA® tablets, for oral use) 
13. Cisplatin (CISplatin injection) 
14. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide Tablets, 
USP) 
15. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
16. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
17. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
18. Stereotactic Body Radiation Therapy (SBRT) 


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Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. Ad5 [E1-, E2b-]-CEA 
3. Ad5 [E1-, E2b-]-Brachyury  
4. Ad5 [E1-, E2b-]-MUC1 
5. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L); 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
6. Recombinant yeast-based vaccine expressing the full length human CEA, with a modified gene 
coding sequence to code for a single amino acid substitution (asparagine to aspartic acid) at the 
native protein amino acid position 610 
7. Recombinant yeast-based vaccine expressing the human Brachyury oncoprotein 
8. NK-92 [CD16.158V, ER IL2] cells  
9. N-803, recombinant human superagonist IL-15 complex  
(also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex) 
Approved Products: 
10. Avelumab 
11. Bevacizumab 
12. Capecitabine 
13. Cisplatin 
14. Cyclophosphamide (anhydrous) 
15. Fluorouracil, USP 
16. Leucovorin (calcium salt) 
17. Paclitaxel, USP 
18. Radiation 
Title of Study: 
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. 
Study Number: 
QUILT-3.067 


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Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT TNBC vaccine 
regimen in subjects with TNBC who have progressed on or after standard-of-care (SoC) 
therapy. 
• 
Secondary objectives are to obtain preliminary estimates of efficacy by objective response 
rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response 
(DOR), disease control rate (DCR), and quality of life (QoL) by patient-reported outcomes 
(PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles (genomics, 
transcriptomics, and proteomics), therapy-induced changes in immune responses; and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT TNBC vaccine regimen as 
assessed by ORR using RECIST Version 1.1 based on Blinded Independent Central 
Review (BICR). 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses; and their correlations with subject outcomes. 
Study Design: 
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. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. Preliminary 
assessment of the safety of the treatment regimen will occur by the NantKwest Safety Review 
Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 3 subjects 
suggest that the combination therapy is tolerable. 
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 confirmed 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 confirmed PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 


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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. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology analyses, as described in Section 6.4.2. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or 
magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related response criteria 
(irRC). In order to document PD, unscheduled tumor assessments may be done if the Investigator 
observes any signs and symptoms of PD. Experimental treatment may continue and an imaging 
assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4–6 weeks 
after the initial response. Subjects who withdraw from the study for reasons other than progression are 
encouraged not to initiate another anticancer treatment unless/until progression has been documented at 
a follow-up visit. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on formalin-fixed, paraffin-embedded (FFPE) 
tumor tissue and whole blood (subject-matched normal comparator against the tumor tissue) collected 
prior to treatment on this study, as described in Section 3.1.1. More information on the collection of 
tumor tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples 
for the exploratory tumor molecular profiling. 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year.  
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV), for the first 2 cycles only  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (32 mg/m2 IV) 
Days 1–5, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   


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• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) 
(1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC])  
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury) 
(40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (100 mg/m2 IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for up 
to 4 cycles) 
Days 8–12, every 3 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
N-803 (15 μg/kg SC) 
• 
Avelumab (10 mg/kg IV) 
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 15, every 3 weeks: 
• 
Nab-paclitaxel (100 mg IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for up 
to 4 cycles) 
Day 16, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 4-week cycles consisting of 
2 weeks of treatment followed by a 2-week rest period. 
Each cycle will consist of the following dosing regimen: 
Day 1, every 4 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 4 weeks: 


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• 
Cyclophosphamide (25 mg PO BID) 
Days 1, 3, and 5, every 4 weeks: 
• 
Capecitabine (650 mg/m2 PO BID, up to a maximum of 1,000 mg per dose) 
Day 2, every 2 weeks:  
• 
N-803 (15 µg/kg SC) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV)  
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-051 (Brachyury), ETBX-061 (MUC1) 
(1 × 1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), GI-6301 (Brachyury) 
(40 YU/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
Days 8–12, every 4 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
If a subject has had a dose reduction for any agent in the induction phase and that dose is lower than the 
maintenance phase starting dose for that agent, the subject may continue receiving the lower dose in the 
maintenance phase. 
Phase 1b 
Primary Endpoint: 
• 
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. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 


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Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 and 
irRC. 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter for 
the conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 23 subjects will be enrolled in the first stage of Simon’s two-stage optimal design. If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 32 subjects will 
be enrolled in the second stage, for a total of 55 subjects in the phase 2 portion of the study. The 
maximum total enrollment for the study is 79 subjects. 
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 other approved standard of care therapy) or subject 


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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 ≥ 1.0 cm. 
6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent 
anticancer treatment 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. 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 for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, 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: 
a. Absolute neutrophil count (ANC) < 1,000 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 


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f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or 
>10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. 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. 


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Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
100 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ETBX-011 (CEA) 
1 × 1011 VP/dose  
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose  
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose  
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
N-803 
15 µg/kg  
SC 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID, up to a maximum 
of 1,000 mg per dose 
PO 
Cisplatin 
32 mg/m2  
IV 
Cyclophosphamide  
25 mg BID (days 1–5) 
25 mg daily (days 8–12) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (day 1 of induction); 
100 mg (day 15 of induction and 
day 1 of maintenance) 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation 
oncologist) 
External beam radiation 
Duration of Treatment: 
• 
Induction phase: Up to 1 year. 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase) or until they experience 
progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw consent, or if 
the Investigator feels it is no longer in their best interest to continue treatment. 


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Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed for: 
• 
CT or MRI scan assessment (see Section 6.1.2) 
• 
Collection of vital status every 90 days (± 14 days) 
Subjects should be followed until either death (any cause) or for a minimum of 24 months past 
administration of the first dose of study drug.  
Following documented PD, subjects may continue to be followed by the investigational physician or a 
third party by phone or review of medical records until withdrawal of consent, lost to follow-up, or 
death (by any cause). Additional information from a subject’s medical records relevant to this study 
may be provided to NantKwest as needed to understand the safety and efficacy of the regimen tested in 
this protocol. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time of their first study 
treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in accordance 
with RECIST Version 1.1 and irRC. In order to document PD, unscheduled tumor assessments may be 
done if the Investigator observes any signs and symptoms of PD. Experimental treatment may continue 
and an imaging assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For responding subjects (PR or CR), a confirmatory response assessment should be done 4-6 weeks 
after the initial response. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Breast Cancer (FACT-B) instrument on study day 1, every 6 weeks thereafter (day 1 of 
weeks 7, 13, 19, etc) prior to treatment, during induction phase, every 12 weeks during maintenance, 
and at the end-of-treatment (EOT) visit. 
Exploratory Analysis: 
Tumor Molecular Profiling: Genomic sequencing of tumor cells from tissue relative to non-tumor 
cells from whole blood will be conducted to identify tumor-specific genomic variances that may 
contribute to disease progression and/or response to treatment. RNA sequencing will be conducted to 
provide expression data and give relevance to DNA mutations. Quantitative proteomics analysis will be 
conducted to determine the absolute amounts of specific proteins, to confirm expression of genes that 
are correlative of disease progression and/or response, and to determine the cutoff values for response. 
Immunologic Analysis: Immune responses to the NANT TNBC vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject outcomes 
will be assessed. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with TNBC whose tumors have progressed on or after SoC treatment. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles and therapy-induced changes in immune responses with 
subject outcomes will be explored. 
 


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Figure 1: 
Study Treatment Schema 
 


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Figure 2: 
Induction Phase Treatment Schema 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 
 


NANT TNBC Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.067 Amendment 5 
APPENDIX 2. 
SPONSOR SIGNATURE 
Study 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. 
Study Number: 
QUILT-3.067 
Version Number: 
6 
Final Date: 
25 March 2019 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
//---/ 
./ 
/ 
Senior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-63 91 
Confidential and Proprietary 
158 
Date: 
/