Clinical trial NCT03136406
Conditions: Pancreatic Cancer
Sponsor: ImmunityBio, Inc.
Start date: 2017-08-11; Completion date: 2019-11-01
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Detailed description:
Treatment will be administered in two phases. Subjects will continue treatment until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or the investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) will enter phase 2 of the study. Subjects may remain on phase 2 of the study for up to 1 year. Treatment will continue throughout phase 2 until the subject experiences PD or unacceptable toxicity, withdraws consent, or the investigator feels it is no longer in the subject's best interest to continue treatment.

Arms: arm 1: A combination of agents will be administered to subjects in this study:

cyclophosphamide, oxaliplatin, capecitabine, fluorouracil, leucovorin, nab-paclitaxel, bevacizumab, avelumab, ALT-803, aNK, GI-4000, and ETBX-011.
Interventions: intervention 1: Cyclophosphamide intervention 2: Oxaliplatin intervention 3: Capecitabine intervention 4: 5-Fluorouracil intervention 5: Leucovorin intervention 6: nab-paclitaxel intervention 7: bevacizumab intervention 8: avelumab intervention 9: ALT-803 intervention 10: aNK for Infusion intervention 11: ETBX-011 intervention 12: GI-4000
Intervention descriptions: intervention 1: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate intervention 2: cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum intervention 3: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine intervention 4: 5-fluoro-2,4 (1H,3H)-pyrimidinedione intervention 5: 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 6: 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 7: Recombinant human anti-VEGF IgG1 monoclonal intervention 8: Recombinant human anti-PD-L1 IgG1 monoclonal antibody intervention 9: Recombinant human super agonist interleukin-15 (IL-15) complex intervention 10: NK-92 cells intervention 11: Ad5 \[E1-, E2b-\]-CEA intervention 12: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins

Protocol documents:
Prot_SAP_000.pdf: 
NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
NANT PANCREATIC CANCER VACCINE: 
COMBINATION IMMUNOTHERAPY IN SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
 
Study Number: 
QUILT-3.039 
IND Sponsor: 
NantCell, 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 
16 March 2017 
Confidential and Proprietary 
1 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki.  The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement.  The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantCell and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
Confidential and Proprietary 
2 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantCell, Inc. 
Name of Investigational Products: 
Approved 
1. CYCLOPHOSPHAMIDE tablets, for oral use 
2. ELOXATIN® (oxaliplatin) injection for intravenous (IV) use 
3. XELODA (capecitabine) tablets, for oral use 
4. Fluorouracil Injection, for IV use 
5. LEUCOVORIN Calcium for Injection, for IV or IM use 
6. ABRAXANE® (Nab-paclitaxel) for injectable suspension 
7. AVASTIN (Bevacizumab) solution for IV infusion 
Investigational  
1. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
2. aNK™, NK-92 ( activated natural killer cell line, aNK™ for Infusion) 
3. ETBX-011: Ad5 [E1-, E2b-]-CEA (carcinoembryonic antigen) 
4. Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody  
5. GI-4000, a vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing 
mutant Ras proteins 
6. Trabedersen (AP 12009), TGF-β2-Specific phosphorothioate antisense oligonucleotide 
Confidential and Proprietary 
3 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Name of Active Ingredients: 
Approved 
1. 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide 
monohydrate (cyclophosphamide) 
2. cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N’] [oxalato(2-)- O,O’] platinum 
(oxaliplatin) 
3. 5’-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine (capecitabine) 
4. 5-fluoro-2,4 (1H,3H)-pyrimidinedione (5-Fluorouracil) 
5. 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 (leucovorin) 
6. 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 (nab-paclitaxel) 
7. Recombinant human anti-VEGF IgG1 monoclonal (bevacizumab) 
Investigational  
1. Recombinant human super agonist interleukin-15 (IL-15) complex (ALT-803) 
2. NK-92 cells (aNK for Infusion) 
3. Ad5 [E1-, E2b-]-CEA 
4. Recombinant human anti-PD-L1 IgG1 monoclonal antibody (avelumab) 
5. GI-4000 Ras vaccine 
6. TGF-β2-specific phosphorothioate antisense oligonucleotide 
Title of Study:  
NANT Pancreatic Cancer Vaccine: combination immunotherapy in subjects with pancreatic cancer 
who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.039 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Confidential and Proprietary 
4 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT regimen in 
subjects with pancreatic cancer who have progressed 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 patient-reported outcomes (PROs) of 
pancreatic cancer symptoms. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT regimen as assessed by 
ORR. 
• 
The secondary objectives are to determine additional measures of efficacy (PFS, DOR, 
DCR, PROs of pancreatic cancer symptoms), and additional safety data. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
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 first line therapy and 
chemotherapy.  Phase 2 will be based on 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 until they experience progressive disease (PD) or 
experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or the 
investigator feels it is no longer in the subject’s best interest to continue treatment.  Those who have a 
complete response (CR) in the induction phase will enter the maintenance phase of the study.  
Subjects may remain on the maintenance phase of the study for up to 1 year.  Treatment will continue 
throughout the maintenance phase until the subject experiences PD or unacceptable toxicity, 
withdraws consent, or the investigator feels it is no longer in the subject’s best interest to continue 
treatment. 
Tumor biopsies and tumor molecular profiling will be conducted at screening and at the end of the 
initial induction (8 weeks) and during a potential prolonged induction phase (depending on response).  
In addition, during routine weekly blood draws, a separate blood tube will be collected to analyse 
blood for changes in circulating RNA. 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 3 months during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography (PET) of target and non-target 
lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and 
immune-related response criteria (irRC).  
Induction Phase: 
The induction phase will consist of repeated 2 week cycles of low-dose radiation and metronomic 
chemotherapy.  The treatment regimen of cyclophosphamide, oxaliplatin, 5-FU/leucovorin, nab-
paclitaxel, trabedersen, bevacizumab, ALT-803, aNK, vaccines (Ad5 and GI-4000), and avelumab 
will be repeated every 2 weeks.  Concurrent stereotactic body radiotherapy (SBRT) will be given 
during the first four 2-week cycles.  Radiation will be administered to all feasible tumor sites using 
SBRT.  Techniques allowed include linear-accelerator based therapies (3D and intensity-modulated 
radiation therapy [IMRT]) and gamma and cyber knife. 
The induction treatment will continue until the subject experiences PD or unacceptable toxicity (not 
correctable with dose reduction), withdraws consent, or the investigator feels it is no longer in the 
subject’s best interest to continue treatment.  Subjects that have a CR in the induction phase will enter 
the maintenance phase of the study.  Response assessments using CT/MRI evaluated according to 
RECIST Version 1.1 and irRC will be performed every 8 weeks during the induction phase. 
Days 1–4 every 2 weeks:  
• Trabedersen (140 mg/m2/day over 24 hours as a continuous infusion). 
Days 1–5 and 8–12, every 2 weeks:  
• 
Cyclophosphamide (50 mg twice a day [BID]). 
Day 1 and 8, every 2 weeks:  
• 
Oxaliplatin (40 mg/m2 IV) 
• 
Nab-paclitaxel (125 mg IV) 
Day 1 every 2 weeks:  
• 
Bevacizumab (5 mg/kg IV) 
Days 1, 3, 5, 8, 10 and 12, every 2 weeks: 
• 
5-fluorouracil (400 mg/m2 over 24 hours as a continuous infusion)   
• 
Leucovorin (20 mg/m2 IV bolus) 
Day 8, 22, 36, 50 (every 2 weeks for 4 doses): 
• 
SBRT (8 Gy) 
Day 9, every 2 weeks:  
• 
ALT-803 (10 μg/kg subcutaneously [SC] 30 minutes prior to aNK infusion) 
 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Day 9 and 11, every 2 weeks:  
• 
aNK (2 x 109 cells/dose IV) 
Day 5, 19, 33 (every 2 weeks for 3 doses then every 8 weeks thereafter):   
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 yeast units [YU] SC; use dependent on genomic sequencing indicating 
required KRAS mutations) 
Day 8, every 2 weeks: 
• 
Avelumab (10 mg/kg IV over 1 h) 
Maintenance Phase: 
The duration of the maintenance phase will be 1 year following completion of the last treatment in the 
induction phase.  Treatment will continue throughout the maintenance phase unless the subject 
experiences PD or unacceptable toxicity, withdraws consent, or the investigator feels it is no longer in 
the subject’s best interest to continue treatment.  Response assessments using CT/MRI evaluated 
according to RECIST Version 1.1 and irRC will be performed every 3 months during the maintenance 
phase. 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (50 mg BID) 
• 
Capecitabine (650 mg/m2 PO BID) 
Day 1, every 2 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Avelumab (10 mg/kg IV over 1 h)  
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC) (30 minutes prior to aNK infusion) 
• 
aNK (2 x 109 cells/dose IV)  
Day 5, every 8 weeks thereafter: 
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 YU SC) 
Confidential and Proprietary 
7 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
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 and irRC. 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months). 
• 
PROs of pancreatic cancer symptoms. 
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes. 
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST and irRC.  
Secondary Endpoints: 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR . 
• 
PROs of pancreatic cancer symptoms. 
• 
 Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 
4.03.  
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes.  
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
Confidential and Proprietary 
8 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
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, 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 33 subjects will be 
enrolled in the second stage, for a total of 56 subjects in the phase 2 portion of the study.  The 
maximum total enrollment will the study is 80 subjects. 
Diagnosis and Main Criteria for Inclusion:  
Inclusion Criteria: 
• 
Age ≥ 18 years old. 
• 
Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
• 
Histologically-confirmed pancreatic cancer with progression on or after SoC therapy. 
• 
ECOG performance status of 0 to 2. 
• 
Have at least 1 measurable lesion and/or non-measurable disease evaluable according to 
RECIST Version 1.1. 
• 
Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anti-cancer treatment and be willing to 
release the specimen for tumor molecular profiling analysis.  If an historic specimen is 
not available, the subject must be willing to undergo a biopsy during the screening 
period. 
• 
Must be willing to provide blood samples for exploratory analyses. 
• 
Ability to attend required study visits and return for adequate follow-up, as required by 
this protocol. 
• 
Agreement to practice effective contraception for female subjects with child-bearing 
potential and non-sterile males.  
Exclusion Criteria: 
• 
History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity 
resulting from previous therapy. 
• 
History of other active malignancies or brain metastasis except: controlled basal cell 
carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of 
prostate cancer that is not under active systemic treatment (except hormonal therapy) and 
with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) 
disease with metastasis in the central hilar area of the chest and involving the pulmonary 
vasculature.  Subjects with a history of another malignancy must have > 5 years without 
evidence of disease. 
• 
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. 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
• 
Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's 
disease, autoimmune disease associated with lymphoma).   
• 
History of organ transplant requiring immunosuppression.   
• 
History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).   
• 
Requires whole blood transfusion to meet eligibility criteria. 
• 
Inadequate organ function, evidenced by the following laboratory results: 
− 
White blood cell (WBC) count < 3,500 cells/mm3  
− 
Absolute neutrophil count < 1,500 cells/mm3. 
− 
Platelet count < 100,000 cells/mm3. 
− 
Hemoglobin < 9 g/dL. 
− 
Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
− 
Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT 
[SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
− 
Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver 
metastases, or >10 × ULN in subjects with bone metastases). 
− 
Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
− 
International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 
or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-
coagulation). 
• 
Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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. 
• 
Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
• 
Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B 
virus (HBV), or hepatitis C virus (HCV). 
• 
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. 
• 
Known hypersensitivity to any component of the study medication(s). 
• 
Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications.  See Excluded Medications list. 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
• 
Participation in an investigational drug study or history of receiving any investigational 
treatment within 14 days prior to screening for this study, except for testosterone-
lowering therapy in men with prostate cancer. 
• 
Assessed by the investigator to be unable or unwilling to comply with the requirements of 
the protocol. 
• 
Concurrent participation in any interventional clinical trial. 
• 
Pregnant and nursing women. 
Investigational Product, Dosage, and Mode of Administration:  
• 
Cyclophosphamide 50 mg BID (induction and maintenance) 
• 
Oxaliplatin 40 mg/m2 IV (induction) 
• 
Trabedersen 140 mg/m2 IV (induction) 
• 
Capecitabine 650 mg/m2 PO BID (maintenance) 
• 
5-FU 400 mg/m2 over 24 hours as a continuous infusion (induction) 
• 
Leucovorin 20 mg/m2 IV bolus (induction) 
• 
Nab-paclitaxel 125 mg IV (induction and maintenance) 
• 
Bevacizumab 5 mg/kg IV (induction and maintenance) 
• 
Avelumab 10 mg/kg IV(induction and maintenance) 
• 
SBRT 8 Gy (induction) 
• 
ALT-803 10 µg/kg SC (induction and maintenance) 
• 
aNK 2 x 109 cells/dose IV (induction and maintenance) 
• 
Ad5 [E1-, E2b-]-CEA 5 x 1011 VP/dose SC (induction and maintenance) 
• 
GI-4000 RAS vaccine 40 YU (induction and maintenance) 
Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum). 
• 
Maintenance phase: 1 year. 
Subjects will be treated until they experience progressive disease, unacceptable toxicity, withdraw 
consent, or if the investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
After discontinuation or completion of the study, subjects will be followed every 3 months for 18 
months to collect follow-up information, including survival status and any current cancer treatment 
regimen.   
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, 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 and will 
be evaluated according to RECIST Version 1.1 and irRC.  OS, DOR, and DCR will also be assessed. 
An assessment of pancreatic cancer symptoms will be conducted via PROs using the Functional 
Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) instrument on 
study day 1, every 28 days thereafter, and at the day 28 follow-up visit. 
Exploratory Analysis: 
Molecular Profiling and Analysis:  
Genomic sequencing of tumor cells from tissue relative to non-tumor cells from whole blood will be 
profiled to identify the genomic variances that may contribute to response or disease progression and 
provide an understanding of molecular abnormalities.  RNA sequencing will be conducted to provide 
expression data and give relevance to DNA mutations.  Quantitative proteomics analysis will be 
conducted to determine the exact amounts of specific proteins and to confirm expression of genes that 
are correlative of response and disease progression.  All genomic, transcriptomic, and proteomic 
molecular analyses will be retrospective and exploratory. 
Plasma will be collected and circulating tumor RNA (ctRNA) will be isolated.  A PCR-based assay 
(LiquidGenomicsDx) will be used to assess the level of PD-L1 circulating RNA.  The levels of 
PD-L1 ctRNA will be correlated with efficacy outcomes.  
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with pancreatic cancer patients whose tumors have progressed on or 
after SoC treatment. 
Results will be presented separately for the induction and maintenance phases of treatment as well as 
overall for the entire treatment regimen.  Overall safety will be assessed by descriptive analyses using 
tabulated frequencies of AEs by grade using CTCAE version 4.03 in terms of treatment-emergent 
AEs, SAEs, and clinically significant changes in safety laboratory tests, physical examinations, 
ECGs, and vital signs. 
ORR will be evaluated according to 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 between genomic/proteomic profiles and efficacy outcomes will be assessed. 
 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
Figure 1: 
Study Treatment Schema 
 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
 
Confidential and Proprietary 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 
 
 
Confidential and Proprietary 
15 




NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
NANT PANCREATIC CANCER VACCINE: 
COMBINATION IMMUNOTHERAPY IN SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
 
Study Number: 
QUILT-3.039 
IND Sponsor: 
NantCell, 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 
16 March 2017 
Version 2 
06 April 2017 
Confidential and Proprietary 
1 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki.  The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement.  The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantCell and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
Confidential and Proprietary 
2 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantCell, Inc. 
Name of Investigational Products: 
Approved 
1. CYCLOPHOSPHAMIDE tablets, for oral use 
2. ELOXATIN® (oxaliplatin) injection for intravenous (IV) use 
3. XELODA (capecitabine) tablets, for oral use 
4. Fluorouracil Injection, for IV use 
5. LEUCOVORIN Calcium for Injection, for IV or IM use 
6. ABRAXANE® (Nab-paclitaxel) for injectable suspension 
7. AVASTIN (Bevacizumab) solution for IV infusion 
Investigational 
1. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
2. aNK™, NK-92 ( activated natural killer cell line, aNK™ for Infusion) 
3. ETBX-011: Ad5 [E1-, E2b-]-CEA (carcinoembryonic antigen) 
4. Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody  
5. GI-4000, a vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing 
mutant Ras proteins 
Confidential and Proprietary 
3 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Name of Active Ingredients: 
Approved 
1. 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate 
(cyclophosphamide) 
2. cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N’] [oxalato(2-)- O,O’] platinum (oxaliplatin) 
3. 5’-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine (capecitabine) 
4. 5-fluoro-2,4 (1H,3H)-pyrimidinedione (5-Fluorouracil) 
5. 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 (leucovorin) 
6. 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 (nab-paclitaxel) 
7. Recombinant human anti-VEGF IgG1 monoclonal (bevacizumab) 
Investigational  
1. Recombinant human super agonist interleukin-15 (IL-15) complex (ALT-803) 
2. NK-92 cells (aNK for Infusion) 
3. Ad5 [E1-, E2b-]-CEA 
4. Recombinant human anti-PD-L1 IgG1 monoclonal antibody (avelumab) 
5. GI-4000 Ras vaccine 
Title of Study:  
NANT Pancreatic Cancer Vaccine: combination immunotherapy in subjects with pancreatic cancer 
who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.039 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Confidential and Proprietary 
4 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT regimen in 
subjects with pancreatic cancer who have progressed 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 patient-reported outcomes (PROs) of 
pancreatic cancer symptoms. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT regimen as assessed by 
ORR. 
• 
The secondary objectives are to determine additional measures of efficacy (PFS, DOR, 
DCR, PROs of pancreatic cancer symptoms), and additional safety data. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
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 first line therapy and 
chemotherapy.  Phase 2 will be based on 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 until they experience progressive disease (PD) or 
experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or the 
investigator feels it is no longer in the subject’s best interest to continue treatment.  Those who have a 
complete response (CR) in the induction phase will enter the maintenance phase of the study.  
Subjects may remain on the maintenance phase of the study for up to 1 year.  Treatment will continue 
throughout the maintenance phase until the subject experiences PD or unacceptable toxicity, 
withdraws consent, or the investigator feels it is no longer in the subject’s best interest to continue 
treatment. 
Tumor biopsies and tumor molecular profiling will be conducted at screening and at the end of the 
initial induction (8 weeks) and during a potential prolonged induction phase (depending on response).  
In addition, during routine weekly blood draws, a separate blood tube will be collected to analyse 
blood for changes in circulating RNA. 
Confidential and Proprietary 
5 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 3 months during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography (PET) of target and non-target 
lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and 
immune-related response criteria (irRC).  
Induction Phase: 
The induction phase will consist of repeated 2 week cycles of low-dose radiation and metronomic 
chemotherapy.  The treatment regimen of cyclophosphamide, oxaliplatin, 5-FU/leucovorin, nab-
paclitaxel, bevacizumab, ALT-803, aNK, vaccines (Ad5 and GI-4000), and avelumab will be 
repeated every 2 weeks.  Concurrent stereotactic body radiotherapy (SBRT) will be given during the 
first four 2-week cycles.  Radiation will be administered to all feasible tumor sites using SBRT.  
Techniques allowed include linear-accelerator based therapies (3D and intensity-modulated radiation 
therapy [IMRT]) and gamma and cyber knife. 
The induction treatment will continue until the subject experiences PD or unacceptable toxicity (not 
correctable with dose reduction), withdraws consent, or the investigator feels it is no longer in the 
subject’s best interest to continue treatment.  Subjects that have a CR in the induction phase will enter 
the maintenance phase of the study.  Response assessments using CT/MRI evaluated according to 
RECIST Version 1.1 and irRC will be performed every 8 weeks during the induction phase. 
Days 1–5 and 8–12, every 2 weeks:  
• 
Cyclophosphamide (50 mg twice a day [BID]). 
Day 1 and 8, every 2 weeks:  
• 
Oxaliplatin (40 mg/m2 IV) 
• 
Nab-paclitaxel (125 mg IV) 
Day 1 every 2 weeks:  
• 
Bevacizumab (5 mg/kg IV) 
Days 1, 3, 5, 8, 10 and 12, every 2 weeks: 
• 
5-fluorouracil (400 mg/m2 over 24 hours as a continuous infusion)   
• 
Leucovorin (20 mg/m2 IV bolus) 
Day 8, 22, 36, 50 (every 2 weeks for 4 doses): 
• 
SBRT (8 Gy) 
Day 9, every 2 weeks:  
• 
ALT-803 (10 μg/kg subcutaneously [SC] 30 minutes prior to aNK infusion) 
Day 9 and 11, every 2 weeks:  
• 
aNK (2 x 109 cells/dose IV) 
 
Confidential and Proprietary 
6 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Day 5, 19, 33 (every 2 weeks for 3 doses then every 8 weeks thereafter):   
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 yeast units [YU] SC; use dependent on genomic sequencing indicating 
required KRAS mutations) 
Day 8, every 2 weeks: 
• 
Avelumab (10 mg/kg IV over 1 h) 
Maintenance Phase: 
The duration of the maintenance phase will be 1 year following completion of the last treatment in the 
induction phase.  Treatment will continue throughout the maintenance phase unless the subject 
experiences PD or unacceptable toxicity, withdraws consent, or the investigator feels it is no longer in 
the subject’s best interest to continue treatment.  Response assessments using CT/MRI evaluated 
according to RECIST Version 1.1 and irRC will be performed every 3 months during the maintenance 
phase. 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (50 mg BID) 
• 
Capecitabine (650 mg/m2 PO BID) 
Day 1, every 2 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Avelumab (10 mg/kg IV over 1 h)  
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC) (30 minutes prior to aNK infusion) 
• 
aNK (2 x 109 cells/dose IV)  
Day 5, every 8 weeks thereafter: 
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 YU SC) 
Confidential and Proprietary 
7 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
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 and irRC. 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months). 
• 
PROs of pancreatic cancer symptoms. 
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes. 
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST and irRC.  
Secondary Endpoints: 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR . 
• 
PROs of pancreatic cancer symptoms. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 
4.03.  
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes.  
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
Confidential and Proprietary 
8 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
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, 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 33 subjects will be 
enrolled in the second stage, for a total of 56 subjects in the phase 2 portion of the study.  The 
maximum total enrollment will the study is 80 subjects. 
Diagnosis and Main Criteria for Inclusion:  
Inclusion Criteria: 
• 
Age ≥ 18 years old. 
• 
Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
• 
Histologically-confirmed pancreatic cancer with progression on or after SoC therapy. 
• 
ECOG performance status of 0 to 2. 
• 
Have at least 1 measurable lesion and/or non-measurable disease evaluable according to 
RECIST Version 1.1. 
• 
Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anti-cancer treatment and be willing to 
release the specimen for tumor molecular profiling analysis.  If an historic specimen is 
not available, the subject must be willing to undergo a biopsy during the screening 
period. 
• 
Must be willing to provide blood samples for exploratory analyses. 
• 
Ability to attend required study visits and return for adequate follow-up, as required by 
this protocol. 
• 
Agreement to practice effective contraception for female subjects with child-bearing 
potential and non-sterile males.  
Exclusion Criteria: 
• 
History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity 
resulting from previous therapy. 
• 
History of other active malignancies or brain metastasis except: controlled basal cell 
carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of 
prostate cancer that is not under active systemic treatment (except hormonal therapy) and 
with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) 
disease with metastasis in the central hilar area of the chest and involving the pulmonary 
vasculature.  Subjects with a history of another malignancy must have > 5 years without 
evidence of disease. 
• 
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. 
Confidential and Proprietary 
9 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
• 
Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's 
disease, autoimmune disease associated with lymphoma).   
• 
History of organ transplant requiring immunosuppression.   
• 
History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).   
• 
Requires whole blood transfusion to meet eligibility criteria. 
• 
Inadequate organ function, evidenced by the following laboratory results: 
− 
White blood cell (WBC) count < 3,500 cells/mm3  
− 
Absolute neutrophil count < 1,500 cells/mm3. 
− 
Platelet count < 100,000 cells/mm3. 
− 
Hemoglobin < 9 g/dL. 
− 
Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
− 
Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT 
[SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
− 
Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver 
metastases, or >10 × ULN in subjects with bone metastases). 
− 
Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
− 
International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 
or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-
coagulation). 
• 
Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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. 
• 
Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
• 
Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B 
virus (HBV), or hepatitis C virus (HCV). 
• 
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. 
• 
Known hypersensitivity to any component of the study medication(s). 
• 
Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications.  See Excluded Medications list. 
Confidential and Proprietary 
10 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
• 
Participation in an investigational drug study or history of receiving any investigational 
treatment within 14 days prior to screening for this study, except for testosterone-
lowering therapy in men with prostate cancer. 
• 
Assessed by the investigator to be unable or unwilling to comply with the requirements of 
the protocol. 
• 
Concurrent participation in any interventional clinical trial. 
• 
Pregnant and nursing women. 
Investigational Product, Dosage, and Mode of Administration:  
• 
Cyclophosphamide 50 mg BID (induction and maintenance) 
• 
Oxaliplatin 40 mg/m2 IV (induction) 
• 
Capecitabine 650 mg/m2 PO BID (maintenance) 
• 
5-FU 400 mg/m2 over 24 hours as a continuous infusion (induction) 
• 
Leucovorin 20 mg/m2 IV bolus (induction) 
• 
Nab-paclitaxel 125 mg IV (induction and maintenance) 
• 
Bevacizumab 5 mg/kg IV (induction and maintenance) 
• 
Avelumab 10 mg/kg IV(induction and maintenance) 
• 
SBRT 8 Gy (induction) 
• 
ALT-803 10 µg/kg SC (induction and maintenance) 
• 
aNK 2 x 109 cells/dose IV (induction and maintenance) 
• 
Ad5 [E1-, E2b-]-CEA 5 x 1011 VP/dose SC (induction and maintenance) 
• 
GI-4000 RAS vaccine 40 YU (induction and maintenance) 
Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum). 
• 
Maintenance phase: 1 year. 
Subjects will be treated until they experience progressive disease, unacceptable toxicity, withdraw 
consent, or if the investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
After discontinuation or completion of the study, subjects will be followed every 3 months for 18 
months to collect follow-up information, including survival status and any current cancer treatment 
regimen.   
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Confidential and Proprietary 
11 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, 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 and will 
be evaluated according to RECIST Version 1.1 and irRC.  OS, DOR, and DCR will also be assessed. 
An assessment of pancreatic cancer symptoms will be conducted via PROs using the Functional 
Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) instrument on 
study day 1, every 28 days thereafter, and at the day 28 follow-up visit. 
Exploratory Analysis: 
Molecular Profiling and Analysis:  
Genomic sequencing of tumor cells from tissue relative to non-tumor cells from whole blood will be 
profiled to identify the genomic variances that may contribute to response or disease progression and 
provide an understanding of molecular abnormalities.  RNA sequencing will be conducted to provide 
expression data and give relevance to DNA mutations.  Quantitative proteomics analysis will be 
conducted to determine the exact amounts of specific proteins and to confirm expression of genes that 
are correlative of response and disease progression.  All genomic, transcriptomic, and proteomic 
molecular analyses will be retrospective and exploratory. 
Plasma will be collected and circulating tumor RNA (ctRNA) will be isolated.  A PCR-based assay 
(LiquidGenomicsDx) will be used to assess the level of PD-L1 circulating RNA.  The levels of 
PD-L1 ctRNA will be correlated with efficacy outcomes.  
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with pancreatic cancer patients whose tumors have progressed on or 
after SoC treatment. 
Results will be presented separately for the induction and maintenance phases of treatment as well as 
overall for the entire treatment regimen.  Overall safety will be assessed by descriptive analyses using 
tabulated frequencies of AEs by grade using CTCAE version 4.03 in terms of treatment-emergent 
AEs, SAEs, and clinically significant changes in safety laboratory tests, physical examinations, 
ECGs, and vital signs. 
ORR will be evaluated according to 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 between genomic/proteomic profiles and efficacy outcomes will be assessed. 
 
Confidential and Proprietary 
12 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
Figure 1: 
Study Treatment Schema 
 
Confidential and Proprietary 
13 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
 
Confidential and Proprietary 
14 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 1 
 
 
Confidential and Proprietary 
15 




NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
NANT PANCREATIC CANCER VACCINE: 
COMBINATION IMMUNOTHERAPY IN SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
 
Study Number: 
QUILT-3.039 
IND Sponsor: 
NantCell, 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 
16 March 2017 
Version 2 
06 April 2017 
Version 3 
03 June 2017 
Confidential and Proprietary 
1 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki.  The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement.  The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantCell and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
Confidential and Proprietary 
2 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantCell, Inc. 
Name of Investigational Products: 
Approved 
1. CYCLOPHOSPHAMIDE tablets, for oral use 
2. ELOXATIN (oxaliplatin) injection for intravenous (IV) use 
3. XELODA (capecitabine) tablets, for oral use 
4. Fluorouracil Injection, for IV use 
5. LEUCOVORIN Calcium for Injection, for IV or IM use 
6. ABRAXANE (Nab-paclitaxel) for injectable suspension 
7. AVASTIN (Bevacizumab) solution for IV infusion 
8. BAVENCIO (avelumab) injection, for IV use 
Investigational 
1. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
2. aNK™, NK-92 ( activated natural killer cell line, aNK™ for Infusion) 
3. ETBX-011: Ad5 [E1-, E2b-]-CEA (carcinoembryonic antigen) 
4. GI-4000, a vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing 
mutant Ras proteins 
Confidential and Proprietary 
3 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Name of Active Ingredients: 
Approved 
1. 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate 
(cyclophosphamide) 
2. cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N’] [oxalato(2-)- O,O’] platinum (oxaliplatin) 
3. 5’-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine (capecitabine) 
4. 5-fluoro-2,4 (1H,3H)-pyrimidinedione (5-Fluorouracil) 
5. 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 (leucovorin) 
6. 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 (nab-paclitaxel) 
7. Recombinant human anti-VEGF IgG1 monoclonal (bevacizumab) 
8. Fully human anti-PD-L1 IgG1 lambda monoclonal antibody (avelumab) 
Investigational  
1. Recombinant human super agonist interleukin-15 (IL-15) complex (ALT-803) 
2. NK-92 cells (aNK for Infusion) 
3. Ad5 [E1-, E2b-]-CEA 
4. GI-4000 Ras vaccine 
Title of Study:  
NANT Pancreatic Cancer Vaccine: combination immunotherapy in subjects with pancreatic cancer 
who have progressed on or after standard-of-care therapy. 
Study Number: 
QUILT-3.039 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Confidential and Proprietary 
4 


NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT regimen in 
subjects with pancreatic cancer who have progressed 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 patient-reported outcomes (PROs) of 
pancreatic cancer symptoms. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT regimen as assessed by 
ORR. 
• 
The secondary objectives are to determine additional measures of efficacy (PFS, DOR, 
DCR, PROs of pancreatic cancer symptoms), and additional safety data. 
• 
Exploratory objectives include determination of any correlations between tumor 
molecular profiles and efficacy, examination of cell phenotypes in tumors and whole 
blood, and assessment of circulating tumor RNA (ctRNA) for detection of PD-L1 
expression. 
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 first line therapy and 
chemotherapy.  Phase 2 will be based on Simon’s two-stage optimal design. 
The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each 
subject to enable the capture and monitoring of any acute and subacute toxicities. 
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, until they experience progressive 
disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw 
consent, or the investigator feels it is no longer in the subject’s best interest to continue treatment.  
Those who have a complete response (CR) in the induction phase will enter the maintenance phase of 
the study.  Subjects may remain on the maintenance phase of the study for up to 1 year.  Treatment 
will continue throughout the maintenance phase until the subject experiences PD or unacceptable 
toxicity, withdraws consent, or the investigator feels it is no longer in the subject’s best interest to 
continue treatment. 
Tumor biopsies and tumor molecular profiling will be conducted at screening and at the end of the 
initial induction (8 weeks) and during a potential prolonged induction phase (depending on response).  
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Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
In addition, circulating RNA and exploratory immune analyses will be carried out on blood collected 
every 4 weeks during the induction phase and every 8 weeks during the maintenance phase. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 3 months during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography (PET) of target and non-target 
lesions in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and 
immune-related response criteria (irRC).  
Induction Phase: 
The induction phase will consist of repeated 2 week cycles of low-dose radiation and metronomic 
chemotherapy.  The treatment regimen of cyclophosphamide, oxaliplatin, 5-FU/leucovorin, 
nab-paclitaxel, bevacizumab, ALT-803, aNK, vaccines (Ad5 and GI-4000), and avelumab will be 
repeated every 2 weeks.  Concurrent stereotactic body radiotherapy (SBRT) will be given during the 
first four 2-week cycles.  Radiation will be administered to all feasible tumor sites using SBRT, as 
described in Section 5.1.5.1.  Techniques allowed include linear-accelerator based therapies (3D and 
intensity-modulated radiation therapy [IMRT]) and gamma and cyber knife. 
The induction treatment will continue for up to 1 year, until the subject experiences PD or 
unacceptable toxicity (not correctable with dose reduction), withdraws consent, or the investigator 
feels it is no longer in the subject’s best interest to continue treatment.  Subjects that have a CR in the 
induction phase will enter the maintenance phase of the study.  Response assessments using CT/MRI 
evaluated in accordance with RECIST Version 1.1 and irRC will be performed every 8 weeks during 
the induction phase. 
Days 1–5 and 8–12, every 2 weeks:  
• 
Cyclophosphamide (50 mg twice a day [BID]). 
Day 1 and 8, every 2 weeks:  
• 
Oxaliplatin (40 mg/m2 IV) 
• 
Nab-paclitaxel (125 mg IV) 
Day 1 every 2 weeks:  
• 
Bevacizumab (5 mg/kg IV) 
Days 1, 3, 5, 8, 10 and 12, every 2 weeks: 
• 
5-fluorouracil (400 mg/m2 over 24 hours as a continuous infusion)   
• 
Leucovorin (20 mg/m2 IV bolus) 
Day 8, 22, 36, 50 (every 2 weeks for 4 doses): 
• 
SBRT (8 Gy) 
Day 9, every 2 weeks:  
• 
ALT-803 (10 μg/kg subcutaneously [SC] 30 minutes prior to aNK infusion) 
 
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Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Day 9 and 11, every 2 weeks:  
• 
aNK (2 x 109 cells/dose IV) 
Day 5, 19, 33 (every 2 weeks for 3 doses then every 8 weeks thereafter):   
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 yeast units [YU] SC, 2 hours after administration of Ad5 [E1-, E2b-]-CEA; 
use dependent on genomic sequencing indicating required KRAS mutations) 
Day 8, every 2 weeks: 
• 
Avelumab (10 mg/kg IV over 1 h) 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase.  Treatment will continue throughout the maintenance phase unless the subject 
experiences PD or unacceptable toxicity, withdraws consent, or the investigator feels it is no longer in 
the subject’s best interest to continue treatment.  Response assessments using CT/MRI evaluated in 
accordance with RECIST Version 1.1 and irRC will be performed every 3 months during the 
maintenance phase. 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (50 mg BID) 
• 
Capecitabine (650 mg/m2 PO BID) 
Day 1, every 2 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Avelumab (10 mg/kg IV over 1 h)  
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC) (30 minutes prior to aNK infusion) 
• 
aNK (2 x 109 cells/dose IV)  
Day 5, every 8 weeks thereafter: 
• 
Ad5 [E1-, E2b-]-CEA (5 x 1011 VP/dose SC) 
• 
GI-4000 (40 YU SC, 2 hours administration of Ad5 [E1-, E2b-]-CEA) 
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Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
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 and irRC. 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months). 
• 
PROs of pancreatic cancer symptoms. 
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes. 
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST and irRC.  
Secondary Endpoints: 
• 
PFS by RECIST and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR . 
• 
PROs of pancreatic cancer symptoms. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 
4.03.  
Exploratory Endpoints: 
• 
Determination of tumor genomic, transcriptomic, and proteomic profiles and correlations 
with subject outcomes.  
• 
Determination of PD-L1 expression from ctRNA and correlation with subject outcomes. 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled.  The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject.  In the phase 2 portion of 
the study, 23 subjects will be enrolled in the first stage of Simon’s two-stage optimal design.  If the 
study proceeds to the second stage of Simon’s two-stage optimal design, an additional 33 subjects 
will be enrolled in the second stage, for a total of 56 subjects in the phase 2 portion of the study.  The 
maximum total enrollment will the study is 80 subjects. 
Diagnosis and Main Criteria for Inclusion:  
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 cancer with progression on or after SoC therapy. 
4. ECOG performance status of 0 to 2. 
5. Have at least 1 measurable lesion of ≥ 1.5 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anti-cancer treatment and be willing to release the 
specimen for tumor molecular profiling analysis.  If an historic specimen is not available, the 
subject must be willing to undergo a biopsy during the screening period. 
7. Must be willing to provide blood samples for exploratory analyses. 
8. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 
9. Agreement to practice effective contraception for female subjects with 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. 
Exclusion Criteria: 
1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity 
resulting from previous therapy. 
2. History of other active malignancies or brain metastasis except: controlled basal cell 
carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior history of 
prostate cancer that is not under active systemic treatment (except hormonal therapy) and 
with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease 
with metastasis in the central hilar area of the chest and involving the pulmonary vasculature.  
Subjects with a history of another malignancy must have > 5 years without evidence of 
disease. 
 
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Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
 
3. 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. 
4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's 
disease, autoimmune disease associated with lymphoma).   
5. History of organ transplant requiring immunosuppression.   
6. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).   
7. Requires whole blood transfusion to meet eligibility criteria. 
8. Inadequate organ function, evidenced by the following laboratory results: 
a. White blood cell (WBC) count < 3,500 cells/mm3  
b. Absolute neutrophil count < 1,500 cells/mm3. 
c. Platelet count < 100,000 cells/mm3. 
d. Hemoglobin < 9 g/dL. 
e. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
f. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
g. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
h. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
i. 
International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or 
partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation). 
9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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. 
10. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus 
(HBV), or hepatitis C virus (HCV). 
12. 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. 
13. Known hypersensitivity to any component of the study medication(s). 
14. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications.  See Excluded Medications list. 
 
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Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
15. Participation in an investigational drug study or history of receiving any investigational 
treatment within 14 days prior to screening for this study, except for testosterone-lowering 
therapy in men with prostate cancer. 
16. Assessed by the investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 
Investigational Product, Dosage, and Mode of Administration:  
• 
Cyclophosphamide 50 mg BID (induction and maintenance) 
• 
Oxaliplatin 40 mg/m2 IV (induction) 
• 
Capecitabine 650 mg/m2 PO BID (maintenance) 
• 
5-FU 400 mg/m2 over 24 hours as a continuous infusion (induction) 
• 
Leucovorin 20 mg/m2 IV bolus (induction) 
• 
Nab-paclitaxel 125 mg IV (induction and maintenance) 
• 
Bevacizumab 5 mg/kg IV (induction and maintenance) 
• 
Avelumab 10 mg/kg IV(induction and maintenance) 
• 
SBRT 8 Gy (induction) 
• 
ALT-803 10 µg/kg SC (induction and maintenance) 
• 
aNK 2 x 109 cells/dose IV (induction and maintenance) 
• 
Ad5 [E1-, E2b-]-CEA 5 x 1011 VP/dose SC (induction and maintenance) 
• 
GI-4000 RAS vaccine 40 YU (induction and maintenance) 
Duration of Treatment: 
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum). 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they 
experience progressive disease, unacceptable toxicity, withdraw consent, or if the investigator feels it 
is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
After discontinuation or completion of the study, subjects will be followed every 3 months for 18 
months to collect follow-up information, including survival status and any current cancer treatment 
regimen.   
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, 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 and will 
be evaluated in accordance with RECIST Version 1.1 and irRC.  OS, DOR, and DCR will also be 
assessed. 
An assessment of pancreatic cancer symptoms will be conducted via PROs using the Functional 
Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) instrument on 
study day 1, every 28 days thereafter, and at the day 28 follow-up visit. 
Exploratory Analysis: 
Molecular Profiling and Analysis:  
Genomic sequencing of tumor cells from tissue relative to non-tumor cells from whole blood will be 
profiled to identify the genomic variances that may contribute to response or disease progression and 
provide an understanding of molecular abnormalities.  RNA sequencing will be conducted to provide 
expression data and give relevance to DNA mutations.  Quantitative proteomics analysis will be 
conducted to determine the exact amounts of specific proteins and to confirm expression of genes that 
are correlative of response and disease progression.  All genomic, transcriptomic, and proteomic 
molecular analyses will be retrospective and exploratory. 
Plasma will be collected and circulating tumor RNA (ctRNA) will be isolated.  A PCR-based assay 
(LiquidGenomicsDx) will be used to assess the level of PD-L1 circulating RNA.  The levels of 
PD-L1 ctRNA will be correlated with efficacy outcomes.  
Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with pancreatic cancer patients whose tumors have progressed on or 
after SoC treatment. 
Results will be presented separately for the induction and maintenance phases of treatment as well as 
overall for the entire treatment regimen.  Overall safety will be assessed by descriptive analyses using 
tabulated frequencies of AEs by grade using CTCAE version 4.03 in terms of treatment-emergent 
AEs, SAEs, and clinically significant changes in safety laboratory tests, physical examinations, 
ECGs, 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 between genomic/proteomic profiles and efficacy outcomes will be assessed. 
 
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NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
Figure 1: 
Study Treatment Schema 
 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
 
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NANT Pancreatic Cancer Vaccine 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.039 Amendment 2 
 
 
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