Conditions: Pancreatic Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with pancreatic cancer who have progressed on or after previous Standard of Care (SoC) chemotherapy.

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 were administered to subjects in this study: Aldoxorubicin HCl, ALT-803, ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), ETBX-061 (MUC1), GI-4000, GI-6207, GI-6301, haNK for infusion, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, oxaliplatin, and Stereotactic Body Radiation Therapy (SBRT).

Interventions: intervention 1: Aldoxorubicin HCl intervention 2: ALT-803 intervention 3: ETBX-011 intervention 4: ETBX-021 intervention 5: ETBX-051 intervention 6: ETBX-061 intervention 7: GI-4000 intervention 8: GI-6207 intervention 9: GI-6301 intervention 10: haNK for infusion intervention 11: bevacizumab intervention 12: Capecitabine intervention 13: Cyclophosphamide intervention 14: Fluorouracil intervention 15: Leucovorin intervention 16: nab-Paclitaxel intervention 17: Oxaliplatin intervention 18: Avelumab intervention 19: 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 \[E1-, E2b-\]-HER2 intervention 5: Ad5 \[E1-, E2b-\]-Brachyury intervention 6: Ad5 \[E1-, E2b-\]-MUC1 intervention 7: RAS yeast intervention 8: Carcinoembryonic Antigen (CEA) yeast intervention 9: Brachyury yeast intervention 10: NK-92 \[CD16.158V, ER IL-2\] intervention 11: Recombinant human anti-Vascular Endothelial Growth Factor (VEGF) IgG1 monoclonal intervention 12: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine intervention 13: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate intervention 14: 5-fluoro-2,4 (1H,3H)-pyrimidinedione intervention 15: 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 16: 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 17: cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum intervention 18: Recombinant human anti-programmed death-ligand 1 (PD-L1) IgG1 monoclonal antibody intervention 19: Stereotactic Body Radiation Therapy

Protocol document:
Prot_SAP_000.pdf: 
NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
1 
Title Page 
PHASE 1B/2 TRIAL OF THE NANT PANCREATIC 
CANCER VACCINE AS TREATMENT FOR SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
Study Number: 
QUILT-3.080 
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 
28 June 2018 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
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 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-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine)
5.
ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine)
6.
ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)
7.
GI-4000 (RAS yeast vaccine)
8.
GI-6207 (CEA yeast vaccine)
9.
GI-6301 (Brachyury yeast vaccine)
10. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion)
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for intravenous [IV] use)
12. Bevacizumab (AVASTIN® solution for IV infusion)
13. Capecitabine (XELODA® tablets, for oral use)
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. Oxaliplatin (ELOXATIN® injection for IV use)
19. Stereotactic Body Radiation Therapy (SBRT)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
4 
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-]-HER2
5.
Ad5 [E1-, E2b-]-Brachyury
6.
Ad5 [E1-, E2b-]-MUC1
7.
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)
8.
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
9.
Recombinant yeast based vaccine expressing the human brachyury oncoprotein
10. NK92 [CD16.158V, ER IL2] cells
Approved Products: 
11. Avelumab
12. Bevacizumab
13. Capecitabine
14. Cyclophosphamide (anhydrous)
15. Fluorouracil, USP
16. Leucovorin (calcium salt)
17. Paclitaxel, USP
18. Oxaliplatin, USP
19. Radiation
Title of Study: 
Phase 1b/2 trial of the NANT Pancreatic Cancer Vaccine as treatment for subjects with pancreatic 
cancer who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.080 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
5 
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 Pancreatic
Cancer Vaccine regimen in subjects with pancreatic cancer 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 cancer antigen 19-9 (CA 19-9), 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 Pancreatic Cancer
Vaccine regimen as assessed by ORR using Response Evaluation Criteria in Solid
Tumors (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 CA 19-9, 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 pancreatic cancer who have progressed on or after previous SoC chemotherapy.  
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee after the first 3 subjects have completed the dose-limiting toxicity (DLT) 
assessment period. Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggests that the combination therapy is tolerable. 
In phase 2, subjects will be enrolled into 1 of 2 cohorts: (1) subjects who have failed first-line SoC 
therapy (first-line metastatic or progressed after adjuvant chemotherapy specifically including 
FOLFIRINOX, gemcitabine and nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), 
and (2) subjects who have been treated with more than one line of SoC therapy. In phase 2, ORR will 
be evaluated separately for each cohort using Simon’s two-stage optimal design. 
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 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
6 
the subject’s best interest to continue treatment. Subjects with PD upon radiologic evaluation per 
RECIST Version 1.1 may, at the discretion of the treating physician, continue to receive study 
treatment for additional treatment cycles (ie, continue to receive treatment for up to 6 additional 
weeks following the conclusion of the subject’s current treatment cycle) in case of pseudoprogression. 
If pseudoprogression is observed, subjects are allowed to continue treatment. The maximum time on 
study treatment is 2 years. 
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 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. 
Subjects who withdraw from the trial for reasons other than progression are encouraged not to initiate 
another anticancer treatment unless/until progression has been documented at a follow-up visit.  
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 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. When 
disease progression per RECIST Version 1.1 is initially observed, an imaging assessment should be 
done 4–6 weeks after the initial PD assessment to rule out tumor pseudoprogression. If 
pseudoprogression is observed, subjects are allowed to continue treatment and response assessments 
will continue every 8 or 12 weeks and evaluated per irRC. For subjects exhibiting a response (PR or 
CR), a confirmatory imaging assessment should be done 4–6 weeks after the initial response. 
Prospective Tumor Molecular Profiling 
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, 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. 
RAS mutational status and HER-2 positivity will be used to determine which subjects will receive 
GI-4000 (RAS) and/or ETBX-021 (HER2), respectively. Subjects will receive GI-4000 (RAS) if their 
tumor is positive for specific RAS mutations, as determined by whole genome sequencing. Subjects 
will receive ETBX-021 (HER2) if their tumor is HER2-positive (IHC 3+ or FISH positive), as 
determined by an FDA-approved test. Treatment with all study drugs except GI-4000 (RAS) and 
ETBX-021 (HER2) 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 RAS mutations targeted by GI-4000 (RAS) and/or positive for HER2 by ETBX-021 
(HER2) will begin as soon as molecular profiling results are available. All other agents in the NANT 
Pancreatic Cancer Vaccine regimen will be administered regardless of tumor molecular profile. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
7 
Induction Phase: 
Treatment in the induction phase will consist of repeated 3-week cycles for a maximum treatment 
period of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
•
Bevacizumab (5 mg/kg IV)
Day 1, every 3 weeks: 
•
Leucovorin (20 mg/m2 IV bolus)
•
Nab-paclitaxel (125 mg IV)
•
Oxaliplatin (40 mg/m2 IV)
Days 1–5, every 3 weeks: 
•
5-FU (1,500 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-021 (HER2), ETBX-051 (Brachyury),
and ETBX-061 (MUC1) (1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC])
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) will be
administered, as described above.
Day 8, every 3 weeks: 
•
Aldoxorubicin HCl (80 mg/m2 IV)
•
Oxaliplatin (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: 
•
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 11, every 3 weeks for 3 cycles and every 9 weeks thereafter: 
•
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury)
(40 yeast units [YU]/vaccine/dose SC)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
8 
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be 
administered, as described above. 
Day 15, every 3 weeks for 2 cycles: 
•
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist)
Day 16, every 3 weeks: 
•
haNK (2 × 109 cells/dose IV)
Day 18, every 3 weeks: 
•
haNK (2 × 109 cells/dose IV)
Maintenance Phase: 
Treatment in the maintenance phase will consist of repeated 2-week cycles for up to 1 year following 
completion of the last treatment in the induction phase, as follows: 
Day 1, every 2 weeks: 
•
Aldoxorubicin HCl (60 mg/m2 IV)
•
Nab-paclitaxel (100 mg IV)
Day 1, every 12 weeks thereafter: 
•
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury),
and ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC)
•
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (40
YU/vaccine/dose SC)
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) and
GI-4000 (RAS) will be administered, as described above.
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)
•
haNK (2 × 109 cells/dose IV)
Days 8–12, every 2 weeks: 
•
Cyclophosphamide (25 mg PO daily)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
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
and irRC.
•
QoL by PROs.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
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.


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
10 
•
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version
4.03.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
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 response will be assessed by 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. 
In the phase 2 portion of the study, ORR will be evaluated separately using Simon’s two-stage 
optimal design for cohorts that include: (1) subjects who have failed first-line SoC therapy (first-line 
metastatic or progressed after adjuvant chemotherapy specifically including FOLFIRINOX, 
gemcitabine and nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), and (2) subjects 
who have been treated with more than one line of SoC therapy. 
For cohort 1, 37 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 57 subjects 
will be enrolled in the second stage, for a total of 94 subjects in the phase 2 portion of the study for 
cohort 1.  
For cohort 2, 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 for 
cohort 2.  
The maximum total enrollment for the study is 173 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 pancreatic adenocarcinoma with progression on or after SoC
therapy.
4.
ECOG performance status of 0 to 2.
5.
Have at least 1 measurable lesion of ≥ 1.0 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,


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
11 
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 < 1,000 cells/mm3.
b.
Platelet count < 75,000 cells/mm3.
c.
Total bilirubin greater than 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.
h.
Medically uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
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.


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 
Confidential and Proprietary 
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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 14 days prior to initiation of treatment on this study, except for receipt of
testosterone-lowering therapy in men with prostate cancer, or treatment with any NANT
Cancer Vaccine therapy.
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-021 (HER2) 
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 


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Products, Dosage, and Mode of Administration: 
Investigational Products 
Investigational Products 
Investigational Products 
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 
Cyclophosphamide 
25 mg BID (days 1-5 of induction 
and maintenance); 
25 mg daily (days 8-12 of induction 
and maintenance) 
PO 
5-FU 
1,500 mg/m2 
85-hour to 96-hour 
continuous IV infusion 
Leucovorin 
20 mg/m2 
IV bolus 
Nab-paclitaxel 
125 mg (induction); 
100 mg (maintenance) 
IV 
Oxaliplatin 
40 mg/m2 (day 1 of induction); 
20 mg/m2 (day 8 of induction) 
IV 
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 confirmed 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 imaging and response assessments (see Section 6.1.2)
•
Assessment of serum CA19-9 level (co-incident with CT/MRI assessments)
•
Collection of vital status every 90 days (± 14 days)
Subjects should be followed until either death (any cause) or for a minimum of 18 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 (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.  
OS, DOR, and DCR will also be assessed. 
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. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Hepatobiliary Cancer (FACT-Hep) 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 pancreatic cancer 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. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and efficacy of metronomic combination 
therapy in subjects with pancreatic cancer 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 and presented separately for cohorts 1 and 2. 
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 CA 19-9 level, 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 


NANT Pancreatic Cancer Vaccine 
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Figure 2: 
Induction Phase Treatment Schema 


NANT Pancreatic Cancer Vaccine 
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Figure 3: 
Maintenance Phase Treatment Schema 


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Table 18: Schedule of Events for Induction Phase of Study 
Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visitc 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
General Assessments 
Informed consent 
X 
Inclusion/exclusiond 
X 
Demographics 
X 
Medical historye 
X 
Confirm availability of FFPE 
tumor samplef
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Physical exam: height, weight
g
X 
X 
X 
X 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
X 
X 
12-lead ECGi
X 
Xj 
Every 6 weeks 
X 
ECHO (with ejection fraction) 
X 
X
j 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
FACT-Hep Questionnaire 
X 
X 
Every 6 weeks 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
Chemistry panelk 
X 
X
j 
X 
X 
X 
CA19-9 
X 
X
j 
Every 3 weeks 
X 
Hematologyl 
X 
X
j 
X 
X 
X 


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visitc 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Urinalysis 
X 
X
j 
X 
X 
X 
Pregnancy testm 
X 
X
j 
Every 6 weeks 
X 
Serum virology (HIV)n 
X 
Determine HER2 positivity 
and RAS mutational statuso 
X 
Collect whole blood for tumor 
molecular profilingp 
X 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect whole blood for 
ctDNA/ctRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
Tumor Imaging and Assessments 
CT or MRIs
 
X 
Every 8 weeks 
X 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction 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. Those who have a CR in the induction phase will enter the maintenance phase of the study.  Any required blood draws and safety 
laboratory sample collections (including urinalysis) may be performed within a 3-day window of the time indicated. 
b End-of-treatment visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the Investigator or treating physician and must be recorded in the 
subject’s source documents and on the Unscheduled Visit eCRF. 
d Inclusion/exclusion criteria will also be evaluated at enrollment. 
e Medical history will also be evaluated at enrollment. 


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f Subject’s FFPE tumor tissue sample must be obtained following the conclusion of the most recent anticancer treatment and prior to first study treatment. If not 
available, a fresh tumor biopsy must be performed, if considered safe by the Investigator. In the event a fresh biopsy needs to be scheduled, the site may 
consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose of any study 
drug. 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. Treatment on this study 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 HER2 and specific RAS mutations targeted by GI-4000 
(RAS) will begin as soon as molecular profiling results are available. 
g Height required at screening visit only. Weight on day 1 of each treatment cycle should be used to calculate drug doses. 
h Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is 
receiving an infusion of any study compounds, vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior 
to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion 
assessment of vital signs and subsequently if clinically indicated. 
i 12-lead ECG to be performed in triplicate at screening. 
j Day 1 assessments can be skipped if the screening assessment was performed within 1 week prior to the start of treatment. 
k Chemistry panel to include laboratory assessments noted in Table 17. HbA1c to be assessed in screening blood draw only. 
l Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit.
m Serum pregnancy tests for females of child-bearing potential.
n HIV status to be determined by an approved test.
o Assessment of HER2 positivity and RAS mutational status to determine whether ETBX-021 (HER2) and GI-4000 (RAS) will be administered to the subject, as
described in Section 3.1.1.
p Whole blood for tumor molecular profiling will be collected during the screening period for subjects who have been enrolled in the study. 
q Whole blood for immunology and ctDNA/ctRNA analyses will be collected during the screening period for subjects who have been enrolled in the study, every 
6 weeks in the induction phase during routine blood draws, and at the EOT visit. 
r Historic tumor biopsy specimen for tumor molecular profiling will be collected only for subjects enrolled in the study. If an historic specimen is not available, a 
fresh tumor biopsy must be performed, 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. In the event a fresh biopsy needs to be scheduled, 
the site may consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose 
of any study medications. A tumor biopsy is also required 8 weeks after the start of treatment, if considered safe by the Investigator. 
s Tumor imaging by CT or MRI will be performed at screening and every 8 weeks thereafter in the induction phase, as described in Section 6.1.2. 


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Table 19: 
Schedule of Events for Maintenance Phase of Study 
Maintenance Phase Treatment (repeats every 2 weeks, except where noted)a 
Study Week 
1 
2 
EOT Visitb 
Unscheduled 
Visitc 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Concomitant medications 
X 
X 
X 
Physical exam, weight 
X 
X 
X 
Vital signsd 
X 
X 
X 
X 
ECOG performance status 
X 
X 
12-lead ECG
X 
Every 12 weeks 
X 
ECHO (with ejection fraction) 
X 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
Adverse event collection 
X 
X 
X 
X 
FACT-Hep questionnaire 
X 
Every 12 weeks 
X 
Laboratory Assessments 
Chemistry panele 
X 
X 
CA19-9 
X 
Every 4 weeks 
X 
Hematologyf 
X 
X 
Urinalysis 
X 
X 
Pregnancy testg 
X 
Every 12 weeks 
X 
Collect whole blood for 
immunology analysish 
X 
Every 8 weeks during routine blood draws 
X 
Collect whole blood for 
ctDNA/ctRNA analysish 
X 
Every 8 weeks during routine blood draws 
X 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion 
Tumor Imaging and Assessments 
 CT or MRIi 
X 
Every 12 weeks 
X 


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a Subjects will remain in 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 feels it is no longer in the subject’s best 
interest to continue treatment. Any required blood draws and safety laboratory sample collections (including urinalysis) may be performed within a 3-day 
window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is 
receiving an infusion of any study compounds, vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior 
to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion 
assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and ctDNA/ctRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
 CT or MRIi 
Tumor imaging by CT or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6.1.2. 


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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Title Page 
PHASE 1B/2 TRIAL OF THE NANT PANCREATIC 
CANCER VACCINE AS TREATMENT FOR SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
Study Number: 
QUILT-3.080 
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 
28 June 2018 
Version 2 
15 August 2018 
Version 3 
01 October 2018 


NANT Pancreatic Cancer Vaccine 
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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-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] 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)
10. N-803 (also known as ALT-803; recombinant human superagonist interleukin-15 (IL-15)
complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex])
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for intravenous [IV] use)
12. Bevacizumab (AVASTIN® solution for IV infusion)
13. Capecitabine (XELODA® tablets, for oral use)
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. Oxaliplatin (ELOXATIN® injection for IV use)
19. Stereotactic Body Radiation Therapy (SBRT)


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
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Name of Active Ingredients 
Investigational Products: 
1.
Aldoxorubicin HCl
2.
Ad5 [E1-, E2b-]-CEA
3.
Ad5 [E1-, E2b-]-HER2
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
10. N-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as
IL-15N72D:IL-15RαSu/IgG1 Fc complex)
Approved Products: 
11. Avelumab
12. Bevacizumab
13. Capecitabine
14. Cyclophosphamide (anhydrous)
15. Fluorouracil, USP
16. Leucovorin (calcium salt)
17. Paclitaxel, USP
18. Oxaliplatin, USP
19. Radiation
Title of Study: 
Phase 1b/2 trial of the NANT Pancreatic Cancer Vaccine as treatment for subjects with pancreatic 
cancer who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.080 


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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 Pancreatic
Cancer Vaccine regimen in subjects with pancreatic cancer 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 cancer antigen 19-9 (CA 19-9), tumor
molecular profiles (genomics, transcriptomics, and proteomics), therapy-induced changes
in immune responses, and molecular changes in cell-free circulating DNA (cfDNA) and
RNA (cfRNA); and their correlations with subject outcomes.
Phase 2 
•
The primary objective is to determine the efficacy of the NANT Pancreatic Cancer
Vaccine regimen as assessed by ORR using Response Evaluation Criteria in Solid Tumors
(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 CA 19-9, tumor molecular profiles,
therapy-induced changes in immune responses, and molecular changes in cfDNA and
cfRNA; 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 pancreatic cancer who have progressed on or after previous SoC chemotherapy.  
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee after the first 3 subjects have completed the dose-limiting toxicity (DLT) 
assessment period. Enrollment into the phase 1b portion will continue if data from the initial 3 subjects 
suggests that the combination therapy is tolerable. 
In phase 2, subjects will be enrolled into 1 of 2 cohorts: (1) subjects who have failed first-line SoC 
therapy (first-line metastatic or progressed after adjuvant chemotherapy specifically including 
FOLFIRINOX, gemcitabine and nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), 
and (2) subjects who have been treated with more than one line of SoC therapy. In phase 2, ORR will 
be evaluated separately for each cohort using Simon’s two-stage optimal design. 
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 


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subject’s best interest to continue treatment. Subjects with an initial assessment of PD per RECIST 
Version 1.1 may, at the discretion of the Investigator, continue to receive study treatment until PD is 
confirmed as detailed in Section 6.1.2. The maximum time on study treatment is 2 years. 
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. 
Subjects who withdraw from the trial for reasons other than progression are encouraged not to initiate 
another anticancer treatment unless/until progression has been documented at a follow-up visit.  
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 cfDNA/cfRNA 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 RECIST 
Version 1.1 and immune-related response criteria (irRC). Unscheduled tumor assessments should be 
carried out if the Investigator observes any signs or symptoms of PD. When disease progression per 
RECIST Version 1.1 is initially observed, 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, subjects are allowed to continue treatment and 
response assessments will continue every 8 or 12 weeks and be evaluated per irRC. For subjects 
exhibiting a response (PR or CR), a confirmatory imaging assessment should be done 4–6 weeks after 
the initial response. 
Prospective Tumor Molecular Profiling 
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, 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. 
RAS mutational status will be used to determine which subjects will receive GI-4000 (RAS). Subjects 
will receive GI-4000 (RAS) if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. Treatment with all study drugs except GI-4000 (RAS) 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 RAS mutations targeted by 
GI-4000 (RAS) will begin as soon as molecular profiling results are available. All other agents in the 
NANT Pancreatic Cancer Vaccine regimen will be administered regardless of tumor molecular profile. 
Induction Phase: 
Treatment in the induction phase will consist of repeated 3-week cycles for a maximum treatment 
period of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
•
Bevacizumab (5 mg/kg IV)


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
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Day 1, every 3 weeks: 
•
Leucovorin (20 mg/m2 IV bolus)
•
Nab-paclitaxel (125 mg IV)
•
Oxaliplatin (40 mg/m2 IV)
Days 1–5, every 3 weeks: 
•
5-FU (1,500 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-021 (HER2), ETBX-051 (Brachyury), and
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 (RAS) will be
administered, as described above.
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
≤ 4 cycles only)
Days 8–12, every 3 weeks: 
•
Cyclophosphamide (25 mg PO daily)
Day 9, every 3 weeks: 
•
Avelumab (10 mg/kg IV)
•
haNK (2 × 109 cells/dose IV)
•
N-803 (15 μg/kg SC)
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 ≤ 4
cycles only)
Day 16, every 3 weeks: 
•
haNK (2 × 109 cells/dose IV)


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Maintenance Phase: 
Treatment in the maintenance phase will consist of repeated 2-week cycles for up to 1 year following 
completion of the last treatment in the induction phase, as follows: 
Day 1, every 2 weeks: 
•
Aldoxorubicin HCl (60 mg/m2 IV)
•
Nab-paclitaxel (100 mg IV)
Day 1, every 12 weeks thereafter: 
•
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and
ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC)
•
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury)
(40 YU/vaccine/dose SC)
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be
administered, as described above.
Days 1,3, and 5, every 2 weeks: 
•
Capecitabine (650 mg/m2 PO BID; up to a maximum of 1,000 mg per dose)
Days 1–5, every 2 weeks: 
•
Cyclophosphamide (25 mg PO BID)
Day 2, every 2 weeks: 
•
Avelumab (10 mg/kg IV)
•
haNK (2 × 109 cells/dose IV)
•
N-803 (15 µg/kg SC)
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 SD lasting for at least 2 months) by RECIST Version 1.1 and
irRC.
•
QoL by PROs.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
Tumor molecular profiles and correlations with subject outcomes.
•
Therapy-induced changes in immune responses and correlations with subject outcomes.
•
Molecular changes in cfDNA and cfRNA 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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•
Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version
4.03.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
Tumor molecular profiles and correlations with subject outcomes.
•
Therapy-induced changes in immune responses and correlations with subject outcomes.
•
Molecular changes in cfDNA and cfRNA 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. 
In the phase 2 portion of the study, ORR will be evaluated separately using Simon’s two-stage optimal 
design for cohorts that include: (1) subjects who have failed first-line SoC therapy (first-line metastatic 
or progressed after adjuvant chemotherapy specifically including FOLFIRINOX, gemcitabine and 
nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), and (2) subjects who have been 
treated with more than one line of SoC therapy. 
For cohort 1, 37 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 57 subjects will 
be enrolled in the second stage, for a total of 94 subjects in the phase 2 portion of the study for 
cohort 1.  
For cohort 2, 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 for 
cohort 2.  
The maximum total enrollment for the study is 173 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 pancreatic adenocarcinoma with progression on or after SoC therapy.
4.
ECOG performance status of 0 to 2.
5.
Have at least 1 measurable lesion of ≥ 1.0 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


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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 < 1,000 cells/mm3.
b.
Platelet count < 75,000 cells/mm3.
c.
Total bilirubin greater than 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.
h.
Medically uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
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.


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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 14 days prior to initiation of treatment on this study, except for receipt of
testosterone-lowering therapy in men with prostate cancer, or treatment with any
NANT Cancer Vaccine therapy.
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 
100 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ETBX-011 (CEA) 
1 × 1011 VP/dose 
SC 
ETBX-021 (HER2) 
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 


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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 1000 mg per dose 
PO 
Cyclophosphamide 
25 mg BID (days 1-5 of induction 
and maintenance); 
25 mg daily (days 8-12 of induction 
and maintenance) 
PO 
5-FU 
1500 mg/m2 
85-hour 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 
Oxaliplatin 
40 mg/m2 (induction) 
IV 
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 
confirmed progressive disease or 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 imaging and response assessments (see Section 6.1.2)
•
Assessment of serum CA 19-9 level (co-incident with CT/MRI assessments)
•
Collection of vital status every 90 days (± 14 days)
Subjects should be followed until either death (any cause) or for a minimum of 18 months past 
administration of the first dose of study drug. 
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 or MRI 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. 
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. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Hepatobiliary Cancer (FACT-Hep) 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 Pancreatic Cancer Vaccine regimen will be 
evaluated by standard immune assays. Correlations between therapy-induced immune changes and 
subject outcomes will be assessed. 
cfDNA/cfRNA Analysis: cfDNA and cfRNA 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. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and efficacy of metronomic combination 
therapy in subjects with pancreatic cancer 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 and presented separately for cohorts 1 and 2. 
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 CA 19-9 level, tumor molecular profiles, therapy-induced changes in immune 
responses, and molecular changes in cfDNA and cfRNA 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 


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Table 18: Schedule of Events for Induction Phase of Study 
Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visit
c 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
General Assessments 
Informed consent 
X 
Inclusion/exclusion
d 
X 
Demographics 
X 
Medical history
e 
X 
Confirm availability of FFPE 
tumor sample
f
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Physical exam: height, weight
g
X 
X 
X 
X 
X 
X 
Vital signs
h
X 
X 
X 
X 
X 
X 
 X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
X 
X 
12-lead ECG
i
X 
X
j 
Every 6 weeks 
X 
ECHO (with ejection 
fraction) 
X 
Xj 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
FACT-Hep Questionnaire 
X 
X 
Every 6 weeks 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
Chemistry panel
k 
X 
Xj 
X 
X 
X 
CA 19-9 
X 
Xj 
Every 3 weeks 
X 


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visit
c 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Hematology
l 
X 
Xj 
X 
X 
X 
Urinalysis 
X 
Xj 
X 
X 
X 
Pregnancy test
m 
X 
Xj 
Every 6 weeks 
X 
Serum virology (HIV)
n
X 
Determine HER2 positivity 
and RAS mutational status
o 
X 
Collect whole blood for 
tumor molecular profiling
p 
X 
Collect whole blood for 
immunology analysis
q 
X 
Every 6 weeks during routine blood draws 
X 
Collect whole blood for 
cfDNA/cfRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
Tumor biopsy
r 
X 
8 weeks after the start of treatment 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
Tumor Imaging and Assessments 
CT or MRI
s
 
X 
Every 8 weeks 
X 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction 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. Those who have a CR in the induction phase will enter the maintenance phase of the study.  Any required blood draws and safety 
laboratory sample collections (including urinalysis) may be performed within a 3-day window of the time indicated. 
b End-of-treatment visit must be performed 30 (±5) days after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the Investigator or treating physician and must be recorded in the 
subject’s source documents and on the Unscheduled Visit eCRF. 
d Inclusion/exclusion criteria will also be evaluated at enrollment. 


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e Medical history will also be evaluated at enrollment. 
f Subject’s FFPE tumor tissue sample must be obtained following the conclusion of the most recent anticancer treatment and prior to first study treatment. If not 
available, a fresh tumor biopsy must be performed, if considered safe by the Investigator. In the event a fresh biopsy needs to be scheduled, the site may 
consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose of any study 
drug. 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. Treatment on this study 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 (RAS) will begin 
as soon as molecular profiling results are available. 
g Height required at screening visit only. Weight on day 1 of each treatment cycle should be used to calculate drug doses. 
h Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Assessment of vital signs and AEs on day 15 is 
required only if study treatment is administered on that day. Vital signs are to be obtained after the subject has been in a seated resting position for at least 5 
minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is receiving an infusion of any study compounds, 
vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, 
and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if 
clinically indicated. 
i 12-lead ECG to be performed in triplicate at screening. 
j Day 1 assessments can be skipped if the screening assessment was performed within 1 week prior to the start of treatment. For ECG and ECHO assessments 
only, day 1 assessments can be skipped if the screening assessment was performed within 28 days prior to the start of treatment. 
k Chemistry panel to include laboratory assessments noted in Table 17. HbA1c to be assessed in screening blood draw only. 
l Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit.
m Serum pregnancy tests for females of child-bearing potential.
n HIV status to be determined by an approved test.
o Assessment of RAS mutational status to determine whether GI-4000 (RAS) will be administered to the subject, as described in Section 3.1.1. Assessment of
HER2 positivity may be conducted as soon as tumor tissue is available, and results from this assessment will not affect the drug regimen administered to
subjects in this study.
p Whole blood for tumor molecular profiling will be collected during the screening period for subjects who have been enrolled in the study. 
q Whole blood for immunology and cfDNA/cfRNA analyses will be collected during the screening period for subjects who have been enrolled in the study, every 
6 weeks in the induction phase during routine blood draws, and at the EOT visit. 
r Historic tumor biopsy specimen for tumor molecular profiling will be collected only for subjects enrolled in the study. If an historic specimen is not available, a 
fresh tumor biopsy must be performed, 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. In the event a fresh biopsy needs to be scheduled, 
the site may consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose 
of any study medications. A tumor biopsy is also required 8 weeks after the start of treatment, if considered safe by the Investigator. 
s Tumor imaging by CT or MRI will be performed at screening and every 8 weeks in the induction phase, as described in Section 6.1.2. 


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Table 19: 
Schedule of Events for Maintenance Phase of Study 
Maintenance Phase Treatment (repeats every 2 weeks, except where noted)
a 
Study Week 
1 
2 
EOT Visit
b 
Unscheduled 
Visit
c 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Concomitant medications 
X 
X 
X 
Physical exam, weight 
X 
X 
X 
Vital signs
d 
X 
X 
X 
X 
ECOG performance status 
X 
X 
12-lead ECG
X 
Every 12 weeks 
X 
ECHO (with ejection fraction) 
X 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
Adverse event collection 
X 
X 
X 
X 
FACT-Hep questionnaire 
X 
Every 12 weeks 
X 
Laboratory Assessments 
Chemistry panel
e 
X 
X 
CA 19-9 
X 
Every 4 weeks 
X 
Hematology
f 
X 
X 
Urinalysis 
X 
X 
Pregnancy test
g 
X 
Every 12 weeks 
X 
Collect whole blood for 
immunology analysis
h 
X 
Every 8 weeks during routine blood draws 
X 
Collect whole blood for 
cfDNA/cfRNA analysish 
X 
Every 8 weeks during routine blood draws 
X 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion 
Tumor Imaging and Assessments 
CT or MRI
i
X 
Every 12 weeks 
X 


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a Subjects will remain in 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 feels it is no longer in the subject’s best 
interest to continue treatment. Any required blood draws and safety laboratory sample collections (including urinalysis) may be performed within a 3-day 
window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is 
receiving an infusion of any study compounds, vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior 
to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion 
assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and cfDNA/cfRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6.1.2. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
APPENDIX 2. SPONSOR SIGNATURE 
Study Title: 
Phase I b/2 trial of the NANT Pancreatic Cancer Vaccine as 
treatment for subjects with pancreatic cancer who have progressed 
on or after standard-of-care therapy. 
Study Number: 
QUILT-3.080 
Version Number: 
3 
Final Date: 
0 I October 2018 
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: 
. Lee, MD 
Sen· r Vice President Adult Medical Affairs, 
NantK west Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-6391 
Confidential and Proprietary 
166 
Date: 
_ (_ ) 0 !If 


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
1 
Title Page 
PHASE 1B/2 TRIAL OF THE NANT PANCREATIC 
CANCER VACCINE AS TREATMENT FOR SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
Study Number: 
QUILT-3.080 
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 
28 June 2018 
Version 2 
15 August 2018 
Version 3 
01 October 2018 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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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-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] 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)
10. N-803 (also known as ALT-803; recombinant human superagonist interleukin-15 (IL-15)
complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex])
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for intravenous [IV] use)
12. Bevacizumab (AVASTIN® solution for IV infusion)
13. Capecitabine (XELODA® tablets, for oral use)
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. Oxaliplatin (ELOXATIN® injection for IV use)
19. Stereotactic Body Radiation Therapy (SBRT)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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Name of Active Ingredients 
Investigational Products: 
1.
Aldoxorubicin HCl
2.
Ad5 [E1-, E2b-]-CEA
3.
Ad5 [E1-, E2b-]-HER2
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
10. N-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as
IL-15N72D:IL-15RαSu/IgG1 Fc complex)
Approved Products: 
11. Avelumab
12. Bevacizumab
13. Capecitabine
14. Cyclophosphamide (anhydrous)
15. Fluorouracil, USP
16. Leucovorin (calcium salt)
17. Paclitaxel, USP
18. Oxaliplatin, USP
19. Radiation
Title of Study: 
Phase 1b/2 trial of the NANT Pancreatic Cancer Vaccine as treatment for subjects with pancreatic 
cancer who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.080 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
5 
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 Pancreatic
Cancer Vaccine regimen in subjects with pancreatic cancer 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 cancer antigen 19-9 (CA 19-9), tumor
molecular profiles (genomics, transcriptomics, and proteomics), therapy-induced changes
in immune responses, and molecular changes in cell-free circulating DNA (cfDNA) and
RNA (cfRNA); and their correlations with subject outcomes.
Phase 2 
•
The primary objective is to determine the efficacy of the NANT Pancreatic Cancer
Vaccine regimen as assessed by ORR using Response Evaluation Criteria in Solid Tumors
(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 CA 19-9, tumor molecular profiles,
therapy-induced changes in immune responses, and molecular changes in cfDNA and
cfRNA; 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 pancreatic cancer who have progressed on or after previous SoC chemotherapy.  
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee after the first 3 subjects have completed the dose-limiting toxicity (DLT) 
assessment period. Enrollment into the phase 1b portion will continue if data from the initial 3 subjects 
suggests that the combination therapy is tolerable. 
In phase 2, subjects will be enrolled into 1 of 2 cohorts: (1) subjects who have failed first-line SoC 
therapy (first-line metastatic or progressed after adjuvant chemotherapy specifically including 
FOLFIRINOX, gemcitabine and nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), 
and (2) subjects who have been treated with more than one line of SoC therapy. In phase 2, ORR will 
be evaluated separately for each cohort using Simon’s two-stage optimal design. 
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 


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
6 
subject’s best interest to continue treatment. Subjects with an initial assessment of PD per RECIST 
Version 1.1 may, at the discretion of the Investigator, continue to receive study treatment until PD is 
confirmed as detailed in Section 6.1.2. The maximum time on study treatment is 2 years. 
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. 
Subjects who withdraw from the trial for reasons other than progression are encouraged not to initiate 
another anticancer treatment unless/until progression has been documented at a follow-up visit.  
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 cfDNA/cfRNA 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 RECIST 
Version 1.1 and immune-related response criteria (irRC). Unscheduled tumor assessments should be 
carried out if the Investigator observes any signs or symptoms of PD. When disease progression per 
RECIST Version 1.1 is initially observed, 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, subjects are allowed to continue treatment and 
response assessments will continue every 8 or 12 weeks and be evaluated per irRC. For subjects 
exhibiting a response (PR or CR), a confirmatory imaging assessment should be done 4–6 weeks after 
the initial response. 
Prospective Tumor Molecular Profiling 
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, 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. 
RAS mutational status will be used to determine which subjects will receive GI-4000 (RAS). Subjects 
will receive GI-4000 (RAS) if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. Treatment with all study drugs except GI-4000 (RAS) 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 RAS mutations targeted by 
GI-4000 (RAS) will begin as soon as molecular profiling results are available. All other agents in the 
NANT Pancreatic Cancer Vaccine regimen will be administered regardless of tumor molecular profile. 
Induction Phase: 
Treatment in the induction phase will consist of repeated 3-week cycles for a maximum treatment 
period of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
•
Bevacizumab (5 mg/kg IV)


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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Day 1, every 3 weeks: 
•
Leucovorin (20 mg/m2 IV bolus)
•
Nab-paclitaxel (125 mg IV)
•
Oxaliplatin (40 mg/m2 IV)
Days 1–5, every 3 weeks: 
•
5-FU (1,500 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-021 (HER2), ETBX-051 (Brachyury), and
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 (RAS) will be
administered, as described above.
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
≤ 4 cycles only)
Days 8–12, every 3 weeks: 
•
Cyclophosphamide (25 mg PO daily)
Day 9, every 3 weeks: 
•
Avelumab (10 mg/kg IV)
•
haNK (2 × 109 cells/dose IV)
•
N-803 (15 μg/kg SC)
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 ≤ 4
cycles only)
Day 16, every 3 weeks: 
•
haNK (2 × 109 cells/dose IV)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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Maintenance Phase: 
Treatment in the maintenance phase will consist of repeated 2-week cycles for up to 1 year following 
completion of the last treatment in the induction phase, as follows: 
Day 1, every 2 weeks: 
•
Aldoxorubicin HCl (60 mg/m2 IV)
•
Nab-paclitaxel (100 mg IV)
Day 1, every 12 weeks thereafter: 
•
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and
ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC)
•
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury)
(40 YU/vaccine/dose SC)
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be
administered, as described above.
Days 1,3, and 5, every 2 weeks: 
•
Capecitabine (650 mg/m2 PO BID; up to a maximum of 1,000 mg per dose)
Days 1–5, every 2 weeks: 
•
Cyclophosphamide (25 mg PO BID)
Day 2, every 2 weeks: 
•
Avelumab (10 mg/kg IV)
•
haNK (2 × 109 cells/dose IV)
•
N-803 (15 µg/kg SC)
Days 8–12, every 2 weeks: 
•
Cyclophosphamide (25 mg PO daily)


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
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 SD lasting for at least 2 months) by RECIST Version 1.1 and
irRC.
•
QoL by PROs.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
Tumor molecular profiles and correlations with subject outcomes.
•
Therapy-induced changes in immune responses and correlations with subject outcomes.
•
Molecular changes in cfDNA and cfRNA 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.


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
10 
•
Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version
4.03.
Exploratory Endpoints: 
•
CA 19-9 level and correlations with subject outcomes.
•
Tumor molecular profiles and correlations with subject outcomes.
•
Therapy-induced changes in immune responses and correlations with subject outcomes.
•
Molecular changes in cfDNA and cfRNA 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. 
In the phase 2 portion of the study, ORR will be evaluated separately using Simon’s two-stage optimal 
design for cohorts that include: (1) subjects who have failed first-line SoC therapy (first-line metastatic 
or progressed after adjuvant chemotherapy specifically including FOLFIRINOX, gemcitabine and 
nab-paclitaxel, gemcitabine and capecitabine, or gemcitabine alone), and (2) subjects who have been 
treated with more than one line of SoC therapy. 
For cohort 1, 37 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 57 subjects will 
be enrolled in the second stage, for a total of 94 subjects in the phase 2 portion of the study for 
cohort 1.  
For cohort 2, 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 for 
cohort 2.  
The maximum total enrollment for the study is 173 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 pancreatic adenocarcinoma with progression on or after SoC therapy.
4.
ECOG performance status of 0 to 2.
5.
Have at least 1 measurable lesion of ≥ 1.0 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


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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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 < 1,000 cells/mm3.
b.
Platelet count < 75,000 cells/mm3.
c.
Total bilirubin greater than 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.
h.
Medically uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
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.


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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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 14 days prior to initiation of treatment on this study, except for receipt of
testosterone-lowering therapy in men with prostate cancer, or treatment with any
NANT Cancer Vaccine therapy.
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 
100 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ETBX-011 (CEA) 
1 × 1011 VP/dose 
SC 
ETBX-021 (HER2) 
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 


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
Confidential and Proprietary 
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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 1000 mg per dose 
PO 
Cyclophosphamide 
25 mg BID (days 1-5 of induction 
and maintenance); 
25 mg daily (days 8-12 of induction 
and maintenance) 
PO 
5-FU 
1500 mg/m2 
85-hour 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 
Oxaliplatin 
40 mg/m2 (induction) 
IV 
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 
confirmed progressive disease or 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 imaging and response assessments (see Section 6.1.2)
•
Assessment of serum CA 19-9 level (co-incident with CT/MRI assessments)
•
Collection of vital status every 90 days (± 14 days)
Subjects should be followed until either death (any cause) or for a minimum of 18 months past 
administration of the first dose of study drug. 
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 or MRI 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.  
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. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Hepatobiliary Cancer (FACT-Hep) 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 Pancreatic Cancer Vaccine regimen will be 
evaluated by standard immune assays. Correlations between therapy-induced immune changes and 
subject outcomes will be assessed. 
cfDNA/cfRNA Analysis: cfDNA and cfRNA 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. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and efficacy of metronomic combination 
therapy in subjects with pancreatic cancer 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 and presented separately for cohorts 1 and 2. 
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 CA 19-9 level, tumor molecular profiles, therapy-induced changes in immune 
responses, and molecular changes in cfDNA and cfRNA 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 


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Table 18: Schedule of Events for Induction Phase of Study 
Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visit
c 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
General Assessments 
Informed consent 
X 
Inclusion/exclusion
d 
X 
Demographics 
X 
Medical history
e 
X 
Confirm availability of FFPE 
tumor sample
f
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Physical exam: height, weight
g
X 
X 
X 
X 
X 
X 
Vital signs
h
X 
X 
X 
X 
X 
X 
 X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
X 
X 
12-lead ECG
i
X 
X
j 
Every 6 weeks 
X 
ECHO (with ejection 
fraction) 
X 
Xj 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
FACT-Hep Questionnaire 
X 
X 
Every 6 weeks 
X 
Adverse event collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
Chemistry panel
k 
X 
Xj 
X 
X 
X 
CA 19-9 
X 
Xj 
Every 3 weeks 
X 


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a 
Study Week 
1 
2 
3 
EOT 
Visit
b
Unscheduled 
Visit
c 
Study Day 
-28 to -1
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Hematology
l 
X 
Xj 
X 
X 
X 
Urinalysis 
X 
Xj 
X 
X 
X 
Pregnancy test
m 
X 
Xj 
Every 6 weeks 
X 
Serum virology (HIV)
n
X 
Determine HER2 positivity 
and RAS mutational status
o 
X 
Collect whole blood for 
tumor molecular profiling
p 
X 
Collect whole blood for 
immunology analysis
q 
X 
Every 6 weeks during routine blood draws 
X 
Collect whole blood for 
cfDNA/cfRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
Tumor biopsy
r 
X 
8 weeks after the start of treatment 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
Tumor Imaging and Assessments 
CT or MRI
s
 
X 
Every 8 weeks 
X 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction 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. Those who have a CR in the induction phase will enter the maintenance phase of the study.  Any required blood draws and safety 
laboratory sample collections (including urinalysis) may be performed within a 3-day window of the time indicated. 
b End-of-treatment visit must be performed 30 (±5) days after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the Investigator or treating physician and must be recorded in the 
subject’s source documents and on the Unscheduled Visit eCRF. 
d Inclusion/exclusion criteria will also be evaluated at enrollment. 


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e Medical history will also be evaluated at enrollment. 
f Subject’s FFPE tumor tissue sample must be obtained following the conclusion of the most recent anticancer treatment and prior to first study treatment. If not 
available, a fresh tumor biopsy must be performed, if considered safe by the Investigator. In the event a fresh biopsy needs to be scheduled, the site may 
consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose of any study 
drug. 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. Treatment on this study 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 (RAS) will begin 
as soon as molecular profiling results are available. 
g Height required at screening visit only. Weight on day 1 of each treatment cycle should be used to calculate drug doses. 
h Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Assessment of vital signs and AEs on day 15 is 
required only if study treatment is administered on that day. Vital signs are to be obtained after the subject has been in a seated resting position for at least 5 
minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is receiving an infusion of any study compounds, 
vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, 
and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if 
clinically indicated. 
i 12-lead ECG to be performed in triplicate at screening. 
j Day 1 assessments can be skipped if the screening assessment was performed within 1 week prior to the start of treatment. For ECG and ECHO assessments 
only, day 1 assessments can be skipped if the screening assessment was performed within 28 days prior to the start of treatment. 
k Chemistry panel to include laboratory assessments noted in Table 17. HbA1c to be assessed in screening blood draw only. 
l Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit.
m Serum pregnancy tests for females of child-bearing potential.
n HIV status to be determined by an approved test.
o Assessment of RAS mutational status to determine whether GI-4000 (RAS) will be administered to the subject, as described in Section 3.1.1. Assessment of
HER2 positivity may be conducted as soon as tumor tissue is available, and results from this assessment will not affect the drug regimen administered to
subjects in this study.
p Whole blood for tumor molecular profiling will be collected during the screening period for subjects who have been enrolled in the study. 
q Whole blood for immunology and cfDNA/cfRNA analyses will be collected during the screening period for subjects who have been enrolled in the study, every 
6 weeks in the induction phase during routine blood draws, and at the EOT visit. 
r Historic tumor biopsy specimen for tumor molecular profiling will be collected only for subjects enrolled in the study. If an historic specimen is not available, a 
fresh tumor biopsy must be performed, 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. In the event a fresh biopsy needs to be scheduled, 
the site may consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose 
of any study medications. A tumor biopsy is also required 8 weeks after the start of treatment, if considered safe by the Investigator. 
s Tumor imaging by CT or MRI will be performed at screening and every 8 weeks in the induction phase, as described in Section 6.1.2. 


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Table 19: 
Schedule of Events for Maintenance Phase of Study 
Maintenance Phase Treatment (repeats every 2 weeks, except where noted)
a 
Study Week 
1 
2 
EOT Visit
b 
Unscheduled 
Visit
c 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Concomitant medications 
X 
X 
X 
Physical exam, weight 
X 
X 
X 
Vital signs
d 
X 
X 
X 
X 
ECOG performance status 
X 
X 
12-lead ECG
X 
Every 12 weeks 
X 
ECHO (with ejection fraction) 
X 
Every 12 weeks 
X 
Confirm contraceptive 
measures 
X 
Adverse event collection 
X 
X 
X 
X 
FACT-Hep questionnaire 
X 
Every 12 weeks 
X 
Laboratory Assessments 
Chemistry panel
e 
X 
X 
CA 19-9 
X 
Every 4 weeks 
X 
Hematology
f 
X 
X 
Urinalysis 
X 
X 
Pregnancy test
g 
X 
Every 12 weeks 
X 
Collect whole blood for 
immunology analysis
h 
X 
Every 8 weeks during routine blood draws 
X 
Collect whole blood for 
cfDNA/cfRNA analysish 
X 
Every 8 weeks during routine blood draws 
X 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion 
Tumor Imaging and Assessments 
CT or MRI
i
X 
Every 12 weeks 
X 


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a Subjects will remain in 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 feels it is no longer in the subject’s best 
interest to continue treatment. Any required blood draws and safety laboratory sample collections (including urinalysis) may be performed within a 3-day 
window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is 
receiving an infusion of any study compounds, vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior 
to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is discharged. Temperature will be documented each visit at the first pre-infusion 
assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and cfDNA/cfRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6.1.2. 


NANT Pancreatic Cancer Vaccine 
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Clinical Trial Protocol: QUILT-3.080 Amendment 2 
APPENDIX 2. SPONSOR SIGNATURE 
Study Title: 
Phase I b/2 trial of the NANT Pancreatic Cancer Vaccine as 
treatment for subjects with pancreatic cancer who have progressed 
on or after standard-of-care therapy. 
Study Number: 
QUILT-3.080 
Version Number: 
3 
Final Date: 
0 I October 2018 
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: 
. Lee, MD 
Sen· r Vice President Adult Medical Affairs, 
NantK west Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-6391 
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Date: 
_ (_ ) 0 !If