Clinical trial NCT03387098
Conditions: Pancreatic Cancer
Sponsor: ImmunityBio, Inc.
Start date: 2017-12-28; Completion date: 2019-01-15
Enrollment: 4 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 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 will be administered to subjects in this study: Aldoxorubicin HCl, ALT-803, ETBX-011, GI-4000, haNK, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ehtyl esters, oxaliplatin, SBRT.
Interventions: intervention 1: Aldoxorubicin HCl intervention 2: ALT-803 intervention 3: ETBX-011 intervention 4: GI-4000 intervention 5: haNK for infusion intervention 6: avelumab intervention 7: bevacizumab intervention 8: Capecitabine intervention 9: Cyclophosphamide intervention 10: Fluorouracil intervention 11: Leucovorin intervention 12: nab-Paclitaxel intervention 13: lovaza intervention 14: Oxaliplatin intervention 15: 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: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins intervention 5: NK-92 \[CD16.158V, ER IL-2\] intervention 6: Recombinant human anti-PD-L1 IgG1 monoclonal antibody intervention 7: Recombinant human anti-VEGF IgG1 monoclonal intervention 8: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine intervention 9: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate intervention 10: 5-fluoro-2,4 (1H,3H)-pyrimidinedione intervention 11: 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 12: 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 13: Omega-3-acid ethyl esters intervention 14: cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum intervention 15: Stereotactic Body Radiation Therapy

Protocol documents:
Prot_SAP_000.pdf: 
NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
Confidential and Proprietary 
1 
Title Page 
NANT PANCREATIC CANCER VACCINE: 
MOLECULARLY INFORMED INTEGRATED 
IMMUNOTHERAPY COMBINING INNATE HIGH-
AFFINITY NATURAL KILLER (haNK) CELL THERAPY 
WITH ADENOVIRAL AND YEAST-BASED VACCINES 
TO INDUCE T-CELL RESPONSES IN SUBJECTS WITH 
PANCREATIC CANCER WHO HAVE PROGRESSED ON 
OR AFTER STANDARD-OF-CARE THERAPY 
Study Number: 
QUILT-3.070 
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 
10 November 2017 
Version 2 
12 December 2017 
Version 3 
27 December 2017 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
2 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human super agonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA [carcinoembryonic antigen] 
vaccine) 
4. GI-4000 (RAS yeast vaccine) 
5. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
6. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
7. Bevacizumab (AVASTIN® solution for IV infusion) 
8. Capecitabine (XELODA® tablets, for oral use) 
9. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
10. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
11. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
12. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
13. Omega-3-acid ethyl esters (LOVAZA® Capsules, for oral use) 
14. Oxaliplatin (ELOXATIN® injection for IV use) 
15. Stereotactic Body Radiation Therapy (SBRT) 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
4 
Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. 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) 
5. NK92 [CD16.158V, ER IL2] cells 
Approved Products: 
6. Avelumab 
7. Bevacizumab 
8. Capecitabine 
9. Cyclophosphamide (anhydrous) 
10. Fluorouracil, USP 
11. Leucovorin (calcium salt) 
12. Paclitaxel, USP 
13. Omega-3-acid ethyl esters 
14. Oxaliplatin, USP 
15. Radiation 
Title of Study:  
NANT Pancreatic Cancer Vaccine: Molecularly informed integrated immunotherapy combining 
innate high-affinity natural killer (haNK) cell therapy with adenoviral and yeast-based vaccines to 
induce T-cell responses in subjects with pancreatic cancer who have progressed on or after standard-
of-care therapy 
Study Number: 
QUILT-3.070 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
5 
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 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 RECIST Version 1.1. 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in 
subjects with pancreatic cancer who have progressed on or after previous SoC chemotherapy.  
In phase 1b, the initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval 
between each subject to enable the capture and monitoring of any acute and subacute toxicities. 
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
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 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 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
6 
the Investigator’s discretion. Subjects may remain on the maintenance phase of the study for up to 1 
year. Treatment will continue in the maintenance phase until the subject experiences PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 
feels it is no longer in the subject’s best interest to continue treatment. The maximum time on study 
treatment, including both the induction and maintenance phases, is 2 years. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography-computed tomography 
(PET-CT) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid 
Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC). 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood 
(subject-matched normal comparator against the tumor tissue) collected prior to treatment on this 
study. Treatment with all study drugs except GI-4000 may be initiated before FFPE tumor tissue 
and/or results from prospective tumor molecular profiling are available; in the event that this occurs, 
treatment of subjects with tumors positive for specific RAS mutations targeted by GI-4000 will begin 
as soon as molecular profiling results are available. More information on the collection of tumor 
tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples for 
the exploratory tumor molecular profiling. 
Subjects will receive GI-4000 if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. As described in Section 1.6.9, GI-4000 is 4 separate products from the GI-
4000 series (GI-4014, GI-4015, GI- 4016, and GI-4020); each of these expresses a combination of 
mutated RAS oncoproteins. The specific RAS mutation will determine which GI-4000 product will be 
used for treatment (GI-4014 for G12V, GI-4015 for G12C, GI-4016 for G12D, GI-4020 for G12R or 
Q61H, and GI-4014, GI-4015, or GI-4016 for Q61L or Q61R). 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cyclophosphamide, 
Ad5-based vaccine (ETBX-011), 5-FU/leucovorin, yeast-based vaccine (GI-4000), haNK, 
nab-paclitaxel, omega-3-acid ethyl esters, and oxaliplatin will be repeated every 3 weeks. Concurrent 
SBRT will be given during the first two 3-week cycles. Radiation will be administered to no more 
than 5 tumor sites using SBRT, as described in Section 5.1.5.1. 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily: 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
7 
• 
Omega-3-acid ethyl esters (2 g by mouth [PO] twice a day [BID]) 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV)  
Days 1–5 and 15–19, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
Days 1–5, 8–12, and 15–19 every 3 weeks:  
• 
Cyclophosphamide (25 mg PO BID) 
Days 1 and 8, every 3 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Oxaliplatin (40 mg/m2 IV)  
Days 1 and 15, every 3 weeks: 
• 
Leucovorin (20 mg/m2 IV bolus) 
Day 5, every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
ETBX-011 (5 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
Days 8 and 15, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV on day 8 and 30 mg/m2 IV on day 15)  
Days 8 and 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
Days 9 and 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
Days 9, 11, 16, and 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter:  
• 
GI-4000 (40 yeast units [YU] /dose SC)  
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The duration of the maintenance phase can exceed 1 year if the subject 
continues to benefit, per the Investigator’s discretion. The maintenance phase will consist of repeated 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
8 
2-week cycles. The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, 
cyclophosphamide, capecitabine, Ad5-based vaccine (ETBX-011), yeast-based vaccine (GI-4000), 
haNK, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated every 2 weeks. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (2 g PO BID) 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC at least 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV) 
Day 5, every 8 weeks thereafter: 
• 
ETBX-011 (5 × 1011 VP/dose SC) 
• 
GI-4000 (40 YU/dose SC), 2 hours after administration of the Ad5-based vaccine 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 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 stable disease [SD] lasting for at least 2 months) by RECIST 
and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1.  
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months) by RECIST Version 1.1 
and irRC. 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
10 
4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject.  
In the phase 2 portion of the study, 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 ≥ 1.5 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anticancer treatment and be willing to release the 
specimen for prospective and exploratory tumor molecular profiling. If an historic specimen 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
11 
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. 
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 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
12 
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 testosterone-
lowering therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  or 30 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
5 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2  
PO BID 
Cyclophosphamide  
25 mg 
PO BID 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
13 
5-FU 
1500 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 
Omega-3-acid ethyl esters 
2 g 
PO BID 
Oxaliplatin 
40 mg/m2 
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 progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
14 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-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. 
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 tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
 
15 
Figure 1: 
Study Treatment Schema 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
 
16 
Figure 2: 
Induction Phase Treatment Schema 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
 
Confidential and Proprietary 
 
17 
Figure 3: 
Maintenance Phase Treatment Schema 
 


NANT Pancreatic Cancer Vaccine 
NantK west, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 2 
APPENDIX 1. 
SPONSOR SIGNATURE 
Study Title: 
NANT Pancreatic Cancer Vaccine: Molecularly informed integrated 
immunotherapy combining innate high-affinity natural killer (haNK) 
cell therapy with adenoviral and yeast-based vaccines to induce T-cell 
responses in subjects with pancreatic cancer who have progressed on 
or after standard-of-care therapy 
Study Number: 
QUILT-3.070 
Version Number: 
3 
Final Date: 
27 December 2017 
This clinical trial protocol was subject to critical review and has been approved by NantK west. 
The following personnel contributed to writing and/or approving this protocol: 
f 
J 
n H. Lee, MD 
enior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +l-605-610-6391 
Confidential and Proprietary 
163 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
1 
NANT PANCREATIC CANCER VACCINE: 
MOLECULARLY INFORMED INTEGRATED 
IMMUNOTHERAPY COMBINING INNATE HIGH-
AFFINITY NATURAL KILLER (haNK) CELL THERAPY 
WITH ADAPTIVE T-CELL THERAPY (ADENOVIRUS, 
YEAST, FUSION PROTEIN VACCINE) IN SUBJECTS 
WITH PANCREATIC CANCER WHO HAVE 
PROGRESSED ON OR AFTER STANDARD-OF-CARE 
THERAPY 
 
Study Number: 
QUILT-3.070 
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 
10 November 2017 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
2 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
3 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human super agonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA [carcinoembryonic antigen] 
vaccine) 
4. GI-4000 (RAS yeast vaccine) 
5. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
6. Avelumab (BAVENCIO® injection, for IV use) 
7. Bevacizumab (AVASTIN® solution for IV infusion) 
8. Capecitabine (XELODA® tablets, for oral use) 
9. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
10. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
11. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
12. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
13. Omega-3-acid ethyl esters (LOVAZA® Capsules, for oral use) 
14. Oxaliplatin (ELOXATIN® injection for IV use) 
15. Stereotactic Body Radiation Therapy (SBRT) 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
4 
Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. 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) 
5. NK92 [CD16.158V, ER IL2] cells 
Approved Products: 
6. Avelumab 
7. Bevacizumab 
8. Capecitabine 
9. Cyclophosphamide (anhydrous) 
10. Fluorouracil, USP 
11. Leucovorin (calcium salt) 
12. Paclitaxel, USP 
13. Omega-3-acid ethyl esters 
14. Oxaliplatin, USP 
15. Radiation 
Title of Study:  
NANT Pancreatic Cancer Vaccine: Molecularly informed integrated immunotherapy combining 
innate high-affinity natural killer (haNK) cell therapy with adaptive T-cell therapy (adenovirus, yeast, 
fusion protein vaccine) in subjects with pancreatic cancer who have progressed on or after standard-
of-care therapy 
Study Number: 
QUILT-3.070 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
5 
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 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. 
• 
Secondary objectives are to obtain additional measures of safety and efficacy (PFS, OS, 
DOR, DCR, and QoL by PROs). 
• 
Exploratory objectives include the assessment of tumor molecular profiles, therapy-
induced changes in immune responses, and molecular changes in ctDNA and ctRNA; and 
their correlations with subject outcomes. 
Study Design: 
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in 
subjects with pancreatic cancer who have progressed on or after previous SoC chemotherapy. 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. 
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
Treatment will be administered in two phases, an induction and a maintenance phase, as described 
below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be 
discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not 
corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the 
subject’s best interest to continue treatment. Those who have a complete response (CR) in the 
induction phase will enter the maintenance phase of the study. Subjects who experience ongoing 
stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
6 
the Investigator’s discretion. Subjects may remain on the maintenance phase of the study for up to 1 
year. Treatment will continue in the maintenance phase until the subject experiences PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 
feels it is no longer in the subject’s best interest to continue treatment. The maximum time on study 
treatment, including both the induction and maintenance phases, is 2 years. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) of 
target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1 and immune-related response criteria (irRC). 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood 
(subject-matched normal comparator against the tumor tissue) collected prior to treatment on this 
study. Treatment with all study drugs except GI-4000 may be initiated before FFPE tumor tissue 
and/or results from prospective tumor molecular profiling are available; in the event that this occurs, 
treatment of subjects with tumors positive for specific RAS mutations targeted by GI-4000 will begin 
as soon as molecular profiling results are available. More information on the collection of tumor 
tissue and whole blood is described in Section 6.4.1.2 and is similar to the collection of samples for 
the exploratory tumor molecular profiling. 
Subjects will receive GI-4000 if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing. As described in Section 1.6.9, GI-4000 is 4 separate products from the GI-
4000 series (GI-4014, GI-4015, GI- 4016, and GI-4020); each of these expresses a combination of 
mutated RAS oncoproteins. The specific RAS mutation will determine which GI-4000 product will be 
used for treatment (GI-4014 for G12V, GI-4015 for G12C, GI-4016 for G12D, GI-4020 for G12R or 
Q61H, and GI-4014, GI-4015, or GI-4016 for Q61L or Q61R). 
Induction Phase: 
The induction phase will consist of repeated 3-week cycles for a maximum treatment period of 1 year. 
The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, cyclophosphamide, 
Ad5-based vaccine (ETBX-011), 5-FU/leucovorin, yeast-based vaccine (GI-4000), haNK, 
nab-paclitaxel, omega-3-acid ethyl esters, and oxaliplatin will be repeated every 3 weeks. Concurrent 
stereotactic body radiotherapy (SBRT) will be given during the first two 3-week cycles. Radiation 
will be administered to no more than 5 tumor sites using SBRT, as described in Section 5.1.5.1. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
7 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily: 
• 
Omega-3-acid ethyl esters (by mouth [PO] twice a day [BID] [3 × 1 g capsules and 
2 × 1 g capsules]) 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV)  
Days 1–5 and 15–19, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
Days 1–5, 8–12, and 15–19 every 3 weeks:  
• 
Cyclophosphamide (50 mg BID) 
Days 1 and 8, every 3 weeks:  
• 
Nab-paclitaxel (125 mg IV) 
• 
Oxaliplatin (40 mg/m2 IV)  
Days 1 and 15, every 3 weeks: 
• 
Leucovorin (20 mg/m2 IV bolus) 
Day 5 (every 3 weeks for 3 cycles then every 8 weeks thereafter):   
• 
ETBX-011 (5 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
Days 8 and 15, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV on day 8 and 30 mg/m2 IV on day 15)  
Days 8 and 15 (every 3 weeks for 2 cycles): 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
Days 9 and 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC 30 minutes prior to haNK infusion) 
Days 9, 11, 16, and 18, every 3 weeks:  
• 
haNK (2 x 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 8 weeks thereafter:  
• 
GI-4000 (40 yeast units [YU] /dose SC)  
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
8 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The duration of the maintenance phase can exceed 1 year if the subject 
continues to benefit, per the Investigator’s discretion. The maintenance phase will consist of repeated 
2-week cycles. The treatment regimen of aldoxorubicin HCl, ALT-803, avelumab, bevacizumab, 
cyclophosphamide, capecitabine, Ad5-based vaccine (ETBX-011), yeast-based vaccine (GI-4000), 
haNK, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated every 2 weeks. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (PO BID [3 × 1 g capsules and 2 × 1 g capsules]) 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (50 mg BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC, 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 x 109 cells/dose IV) 
Day 5, every 8 weeks thereafter: 
• 
ETBX-011 (5 × 1011 VP/dose SC) 
• 
GI-4000 (40 YU/dose SC), 2 hours after administration of the Ad5-based vaccine 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
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 and irRC. 
• 
PFS by RECIST Version 1.1 and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months). 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1 and irRC.  
Secondary Endpoints: 
• 
PFS by RECIST Version 1.1 and irRC. 
• 
OS. 
• 
DOR. 
• 
DCR (confirmed CR, PR, or SD lasting for at least 2 months). 
• 
QoL by PROs. 
• 
Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 
4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
10 
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 ≥ 1.5 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anticancer treatment and be willing to release the 
specimen for prospective and exploratory tumor molecular profiling. If an historic specimen 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
11 
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 < 900 cells/mm3. 
b. Platelet count < 75,000 cells/mm3. 
c. Total bilirubin greater than twice the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
d. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
e. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
f. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
g. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3. 
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or 
clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or 
myocardial infarction within 6 months prior to first study medication; unstable angina; 
congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac 
arrhythmia requiring medication. To control hypertension, it is recommended to first start 
propranolol SR 80 mg daily prior to initiating other hypertensive medications. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection 
fraction (LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids 
(dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled 
steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in 
subjects who have known contrast allergies is allowed. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
12 
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 testosterone-
lowering therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  or 30 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
5 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2  
PO BID 
Cyclophosphamide  
50 mg 
PO BID 
5-FU 
1500 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 
Omega-3-acid ethyl esters 
5 g 
PO 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
13 
Oxaliplatin 
40 mg/m2 
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 progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
14 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. OS, DOR, and DCR will also be assessed. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-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. 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
15 
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 tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
 
16 
Figure 1: 
Study Treatment Schema 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
 
17 
Figure 2: 
Induction Phase Treatment Schema 
 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 
 
Confidential and Proprietary 
 
18 
Figure 3: 
Maintenance Phase Treatment Schema 


NANT Pancreatic Cancer Vaccine 
Clinical Trial Protocol: QUILT-3.070 
APPENDIX 1. SPONSOR SIGNATURE 
NantK west, Inc. 
Study Title: 
NANT Pancreatic Cancer Vaccine: Molecularly infonned integrated 
immunotherapy combining innate high-affinity natural killer (haNK) 
cell therapy with adaptive T-cell therapy (adenovirus, yeast, fusion 
protein vaccine) in subjects with pancreatic cancer who have 
progressed on or after standard-of-care therapy 
Study Number: 
QUILT-3.070 
Version N um her: 
1 
Final Date: 
10 November 2017 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
/' 
s igRe&.-
John . Lee, MD 
or Vice President Adult Medical Affairs, 
antKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + l-605-610-6391 
Confidential and Proprietary 
160 
Date: 1vfv 13 JiJ/ ?-
/ 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Title Page 
NANT PANCREATIC CANCER VACCINE: 
MOLECULARLY INFORMED INTEGRATED 
IMMUNOTHERAPY COMBINING INNATE HIGH-
AFFINITY NATURAL KILLER (haNK) CELL THERAPY 
WITH ADENOVIRAL AND YEAST-BASED VACCINES 
TO INDUCE T-CELL RESPONSES IN SUBJECTS WITH 
PANCREATIC CANCER WHO HAVE PROGRESSED ON 
OR AFTER STANDARD-OF-CARE THERAPY 
 
Study Number: 
QUILT-3.070 
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 
10 November 2017 
Version 2 
12 December 2017 
Version 3 
20 December 2017 
Version 4 
23 February 2018 
Confidential and Proprietary 
1 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from, or changes to the protocol will take place without prior agreement from 
NantKwest and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
Confidential and Proprietary 
2 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products:  
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human super agonist interleukin-15 (IL-15) complex [also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA [carcinoembryonic antigen] 
vaccine) 
4. GI-4000 (RAS yeast vaccine) 
5. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
1. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
2. Bevacizumab (AVASTIN® solution for IV infusion) 
3. Capecitabine (XELODA® tablets, for oral use) 
4. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
5. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
6. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
7. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
8. Oxaliplatin (ELOXATIN® injection for IV use) 
9. Stereotactic Body Radiation Therapy (SBRT) 
Confidential and Proprietary 
3 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Name of Active Ingredients 
Investigational Products: 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex) 
3. Ad5 [E1-, E2b-]-CEA 
4. 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) 
5. NK92 [CD16.158V, ER IL2] cells 
Approved Products: 
1. Avelumab 
2. Bevacizumab 
3. Capecitabine 
4. Cyclophosphamide (anhydrous) 
5. Fluorouracil, USP 
6. Leucovorin (calcium salt) 
7. Paclitaxel, USP 
8. Oxaliplatin, USP 
9. Radiation 
Title of Study:  
NANT Pancreatic Cancer Vaccine: Molecularly informed integrated immunotherapy combining 
innate high-affinity natural killer (haNK) cell therapy with adenoviral and yeast-based vaccines to 
induce T-cell responses in subjects with pancreatic cancer who have progressed on or after standard-
of-care therapy 
Study Number: 
QUILT-3.070 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design). 
Confidential and Proprietary 
4 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
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 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.  
In phase 1b, the initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval 
between each subject to enable the capture and monitoring of any acute and subacute toxicities. 
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
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 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 
Confidential and Proprietary 
5 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at 
the Investigator’s discretion. Subjects may remain on the maintenance phase of the study for up to 1 
year. Treatment will continue in the maintenance phase until the subject experiences PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 
feels it is no longer in the subject’s best interest to continue treatment. The maximum time on study 
treatment, including both the induction and maintenance phases, is 2 years. 
Exploratory tumor molecular profiling will be conducted on samples collected prior to treatment on 
this study, 8 weeks after the start of treatment, and during potential prolonged induction and 
maintenance phases (depending on response), as described in Section 6.4.1. Separate blood tubes will 
be collected every 6 weeks in the induction phase and every 8 weeks in the maintenance phase during 
routine blood draws for exploratory immunology and ctDNA/ctRNA analyses, as described in 
Section 6.4.2 and Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT), 
magnetic resonance imaging (MRI), or positron emission tomography-computed tomography 
(PET-CT) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid 
Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC). In order to document 
PD, unscheduled tumor assessments may be done if the Investigator observes any signs and 
symptoms of PD.  For responding subjects (PR or CR), a confirmatory response assessment should be 
done at 4 weeks after the initial response. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status, and will be 
used to determine whether GI-4000 will be administered. GI-4000 administration will be initiated as 
soon as results from tumor molecular profiling are available. All subjects will receive all other agents 
regardless of their tumor molecular profile. 
Prospective tumor molecular profiling will be performed on 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. 
Subjects will receive GI-4000 if their tumor is positive for specific RAS mutations, as determined by 
whole genome sequencing.  
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:  
• 
Bevacizumab (5 mg/kg IV)  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Oxaliplatin (40 mg/m2 IV)  
Days 1–5, every 3 weeks: 
 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
Confidential and Proprietary 
6 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
• 
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:   
• 
ETBX-011 (5 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV over 30 minutes)  
• 
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: 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV)  
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter:  
• 
GI-4000 (40 yeast units [YU] /dose SC)  
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. GI-4000 administration will be initiated as soon as 
results from tumor molecular profiling are available. 
Day 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 16, every 3 weeks: 
• 
ALT-803 (10 μg/kg SC at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV)  
Day 18, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV)  
Maintenance Phase: 
Treatment in the maintenance phase will last for up to 1 year following completion of the last 
treatment in the induction phase, as follows: 
Day 1, every 2 weeks:  
Confidential and Proprietary 
7 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID) 
Days 1–5 and 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (10 µg/kg SC at least 30 minutes prior to haNK infusion) 
• 
Avelumab (10 mg/kg IV over 1 hour)  
• 
haNK (2 × 109 cells/dose IV) 
Day 5 (±1 day), every 8 weeks thereafter: 
• 
ETBX-011 (5 × 1011 VP/dose SC) 
• 
GI-4000 (40 YU/dose SC), 2 hours after administration of the Ad5-based vaccine 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
Confidential and Proprietary 
8 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
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. 
Confidential and Proprietary 
9 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
• 
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 the Investigator; 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. 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, 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 
Confidential and Proprietary 
10 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 
10. Agreement to practice effective contraception for female subjects of child-bearing potential 
and non-sterile males. Female subjects of child-bearing potential must agree to use effective 
contraception for up to 1 year after completion of therapy, and non-sterile male subjects must 
agree to use a condom for up to 4 months after treatment. Effective contraception includes 
surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, 
condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence. 
Exclusion Criteria: 
1. Serious uncontrolled concomitant disease that would contraindicate the use of the 
investigational drug used in this study or that would put the subject at high risk for treatment-
related complications. 
2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's 
disease, autoimmune disease associated with lymphoma).   
3. History of organ transplant requiring immunosuppression.   
4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).   
5. Inadequate organ function, evidenced by the following laboratory results: 
a. Absolute neutrophil count < 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 
Confidential and Proprietary 
11 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
medically managed on a stable regimen to control hypertension prior to study entry. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection 
fraction (LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids 
(dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled 
steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in 
subjects who have known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, 
and St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 
inducer (rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational 
treatment within 14 days prior to initiation of treatment on this study, except for testosterone-
lowering therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV over 30 minutes 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
5 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
haNK cells 
2 × 109 cells/dose  
IV 
Confidential and Proprietary 
12 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID 
PO  
Cyclophosphamide  
25 mg BID (days 1–5, induction); 
25 mg daily (days 8–12, induction); 
25 mg BID (maintenance) 
PO 
5-FU 
1500 mg/m2  
85-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, induction); 
20 mg/m2 (day 8, 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 progressive disease, unacceptable toxicity (not corrected with dose reduction), withdraw 
consent, or if the Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed 
every 90 days (± 14 days) for: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT, MRI, or PET-CT scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 18 months 
past administration of the first dose of chemotherapy to the last subject enrolled in the 
study, whichever comes first. 
Subjects may continue to be followed by the investigational physician or a third party by phone or 
review of medical records approximately every 90 days until withdrawal of consent, lost to follow-up, 
or death (by any cause). Additional information from a subject’s medical records relevant to this 
study may be provided to NantKwest as needed to understand the safety and efficacy of the regimen 
tested in this protocol. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 
Confidential and Proprietary 
13 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. In order to document PD, unscheduled tumor 
assessments may be done if the investigator observes any signs and symptoms of PD. For responding 
subjects (PR or CR), a confirmatory response assessment should be done at 4 weeks after the initial 
response.  
OS, DOR, and DCR will also be assessed. In the phase 1b portion of the study, response will be 
assessed by the Investigator; in the phase 2 portion of the study, the primary assessment of response 
will be based on the 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. 
Confidential and Proprietary 
14 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
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 tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 
 
Confidential and Proprietary 
15 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Figure 1: 
Study Treatment Schema 
 
Confidential and Proprietary 
 
16 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Figure 2: 
Induction Phase Treatment Schema 
 
 
Confidential and Proprietary 
 
17 


NANT Pancreatic Cancer Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.070 Amendment 3 
 
Figure 3: 
Maintenance Phase Treatment Schema 
Confidential and Proprietary 
 
18 




1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

7LWOH3DJH
NANT PANCREATIC CANCER VACCINE: 
MOLECULARLY INFORMED INTEGRATED 
IMMUNOTHERAPY COMBINING INNATE HIGH-
AFFINITY NATURAL KILLER (haNK) CELL THERAPY 
WITH ADENOVIRAL AND YEAST-BASED VACCINES 
TO INDUCE T-CELL RESPONSES IN SUBJECTS WITH 
PANCREATIC CANCER WHO HAVE PROGRESSED ON 
OR AFTER STANDARD-OF-CARE THERAPY

Study Number:
QUILT-3.070 
IND Sponsor:
1DQW.ZHVW,QF
-HIIHUVRQ%OYG
&XOYHU&LW\&$
Sponsor Contact:  
(For medical questions/emergencies)
-RKQ+/HH0'
6HQLRU9LFH3UHVLGHQW$GXOW0HGLFDO$IIDLUV
1DQW.ZHVW,QF
-HIIHUVRQ%OYG
&XOYHU&LW\&$
(PDLO-RKQ/HH#1DQWNZHVWFRP
&HOO3KRQH

Protocol Version 
Date
9HUVLRQ
1RYHPEHU
9HUVLRQ
'HFHPEHU


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

STATEMENT OF COMPLIANCE
7KLVWULDOZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWK*RRG&OLQLFDO3UDFWLFH*&3DVGHVFULEHGLQWKH
,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQL]DWLRQ*XLGHOLQH(,&+(DQGLQDFFRUGDQFHZLWK
8QLWHG6WDWHV86&RGHRI)HGHUDO5HJXODWLRQV&)5DSSOLFDEOHWRFOLQLFDOVWXGLHV&)5
3DUW&)53DUW&)53DUWDQG&)53DUWDQGWKHJHQHUDOHWKLFDO
SULQFLSOHVRXWOLQHGLQWKH'HFODUDWLRQRI+HOVLQNL7KHVWXG\ZLOOUHFHLYHDSSURYDOIURPDQ
,QVWLWXWLRQDO5HYLHZ%RDUG,5%SULRUWRFRPPHQFHPHQW7KH3ULQFLSDO,QYHVWLJDWRUZLOODVVXUH
WKDWQRGHYLDWLRQIURPRUFKDQJHVWRWKHSURWRFROZLOOWDNHSODFHZLWKRXWSULRUDJUHHPHQWIURP
1DQW.ZHVWDQGGRFXPHQWHGDSSURYDOIURPWKH,5%H[FHSWZKHUHQHFHVVDU\WRHOLPLQDWHDQ
LPPHGLDWHKD]DUGVWRWKHWULDOSDUWLFLSDQWV
,DJUHHWRHQVXUHWKDWDOOVWDIIPHPEHUVLQYROYHGLQWKHFRQGXFWRIWKLVVWXG\DUHLQIRUPHGDERXW
WKHLUREOLJDWLRQVLQPHHWLQJWKHDERYHFRPPLWPHQWV

3ULQFLSDO,QYHVWLJDWRU

6LJQHGBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB'DWHBBBBBBBBBBBBBB




1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

PROTOCOL SYNOPSIS
Name of Sponsor/Company:
1DQW.ZHVW,QF
Name of Investigational Products:  

$OGR[RUXELFLQK\GURFKORULGH+&O

$/7UHFRPELQDQWKXPDQVXSHUDJRQLVWLQWHUOHXNLQ,/FRPSOH[>DOVRNQRZQDV
,/1',/5Į6X,J*)FFRPSOH[@

(7%;DGHQRYLUXVVHURW\SH>$G@>((E@&($>FDUFLQRHPEU\RQLFDQWLJHQ@
YDFFLQH

*,5$6\HDVWYDFFLQH

KD1.1.>&'9(5,/@6XVSHQVLRQIRU,QIXVLRQKD1.IRU,QIXVLRQ
Name of Approved Products:

$YHOXPDE%$9(1&,2LQMHFWLRQIRULQWUDYHQRXV>,9@XVH

%HYDFL]XPDE$9$67,1VROXWLRQIRU,9LQIXVLRQ

&DSHFLWDELQH;(/2'$WDEOHWVIRURUDOXVH

&\FORSKRVSKDPLGH&\FORSKRVSKDPLGH&DSVXOHVIRURUDOXVHRU&\FORSKRVSKDPLGH
7DEOHWV863
 )OXRURXUDFLO)8)OXRURXUDFLO,QMHFWLRQIRU,9XVHRQO\
 /HXFRYRULQ/(8&2925,1&DOFLXPIRU,QMHFWLRQIRU,9RULQWUDPXVFXODU>,0@XVH
 1DESDFOLWD[HO$%5$;$1(IRU,QMHFWDEOH6XVSHQVLRQ>SDFOLWD[HOSURWHLQERXQGSDUWLFOHV
IRULQMHFWDEOHVXVSHQVLRQ@>DOEXPLQERXQG@
 2PHJDDFLGHWK\OHVWHUV/29$=$&DSVXOHVIRURUDOXVH
 2[DOLSODWLQ(/2;$7,1LQMHFWLRQIRU,9XVH
 6WHUHRWDFWLF%RG\5DGLDWLRQ7KHUDS\6%57


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

Name of Active Ingredients
Investigational Products:

$OGR[RUXELFLQ+&O

$/7UHFRPELQDQWKXPDQVXSHUDJRQLVWLQWHUOHXNLQ,/FRPSOH[DOVRNQRZQDV
,/1',/5Į6X,J*)FFRPSOH[

$G>((E@&($

*,H[SUHVVLQJPXWDWLRQVLQRASDWFRGRQ*9DQGFRGRQ45DQG4/
*,H[SUHVVLQJPXWDWLRQVLQRASDWFRGRQ*&DQGFRGRQ45DQG4/
*,H[SUHVVLQJPXWDWLRQVLQRASDWFRGRQ*'DQGFRGRQ45DQG4/
DQG*,H[SUHVVLQJPXWDWLRQVLQRASDWFRGRQ*5DQGFRGRQ4/DQG
4+

1.>&'9(5,/@FHOOV
Approved Products:

$YHOXPDE

%HYDFL]XPDE

&DSHFLWDELQH

&\FORSKRVSKDPLGHDQK\GURXV
 )OXRURXUDFLO863
 /HXFRYRULQFDOFLXPVDOW
 3DFOLWD[HO863
 2PHJDDFLGHWK\OHVWHUV
 2[DOLSODWLQ863
 5DGLDWLRQ
Title of Study: 
1$173DQFUHDWLF&DQFHU9DFFLQH0ROHFXODUO\LQIRUPHGLQWHJUDWHGLPPXQRWKHUDS\
FRPELQLQJLQQDWHKLJKDIILQLW\QDWXUDONLOOHUKD1.FHOOWKHUDS\ZLWKDGHQRYLUDODQG\HDVW
EDVHGYDFFLQHVWRLQGXFH7FHOOUHVSRQVHVLQVXEMHFWVZLWKSDQFUHDWLFFDQFHUZKRKDYH
SURJUHVVHGRQRUDIWHUVWDQGDUGRIFDUHWKHUDS\
Study Number:
48,/7
Study Phase:
3KDVHE6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQ


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

Study Objectives:
Phase 1b
•
7KHSULPDU\REMHFWLYHLVWRHYDOXDWHWKHRYHUDOOVDIHW\SURILOHRIWKH1$17SDQFUHDWLF
FDQFHUYDFFLQHUHJLPHQLQVXEMHFWVZLWKSDQFUHDWLFFDQFHUZKRKDYHSURJUHVVHGRQRU
DIWHUVWDQGDUGRIFDUH6R&WKHUDS\
•
6HFRQGDU\REMHFWLYHVDUHWRREWDLQSUHOLPLQDU\HVWLPDWHVRIHIILFDF\E\REMHFWLYH
UHVSRQVHUDWH255SURJUHVVLRQIUHHVXUYLYDO3)6RYHUDOOVXUYLYDO26GXUDWLRQRI
UHVSRQVH'25GLVHDVHFRQWUROUDWH'&5DQGTXDOLW\RIOLIH4R/E\SDWLHQWUHSRUWHG
RXWFRPHV352V
•
([SORUDWRU\REMHFWLYHVLQFOXGHWKHDVVHVVPHQWRIWXPRUPROHFXODUSURILOHVJHQRPLFV
WUDQVFULSWRPLFVDQGSURWHRPLFVWKHUDS\LQGXFHGFKDQJHVLQLPPXQHUHVSRQVHVDQG
PROHFXODUFKDQJHVLQFLUFXODWLQJWXPRU'1$FW'1$DQG51$FW51$DQGWKHLU
FRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
Phase 2 
•
7KHSULPDU\REMHFWLYHLVWRGHWHUPLQHWKHHIILFDF\RIWKH1$17SDQFUHDWLFFDQFHU
YDFFLQHUHJLPHQDVDVVHVVHGE\255XVLQJ5(&,679HUVLRQ
•
6HFRQGDU\REMHFWLYHVDUHWRREWDLQDGGLWLRQDOPHDVXUHVRIVDIHW\DQGHIILFDF\3)626
'25'&5DQG4R/E\352V
•
([SORUDWRU\REMHFWLYHVLQFOXGHWKHDVVHVVPHQWRIWXPRUPROHFXODUSURILOHVWKHUDS\
LQGXFHGFKDQJHVLQLPPXQHUHVSRQVHVDQGPROHFXODUFKDQJHVLQFW'1$DQGFW51$DQG
WKHLUFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
Study Design:
7KLVLVDSKDVHEVWXG\WRHYDOXDWHWKHVDIHW\DQGHIILFDF\RIPHWURQRPLFFRPELQDWLRQWKHUDS\LQ
VXEMHFWV ZLWKSDQFUHDWLFFDQFHUZKRKDYHSURJUHVVHGRQRUDIWHUSUHYLRXV6R&FKHPRWKHUDS\
,QSKDVHEWKHLQLWLDOVXEMHFWVZLOOEHHQUROOHGLQDVWDJJHUHGIDVKLRQZLWKDGD\LQWHUYDO
EHWZHHQHDFKVXEMHFWWRHQDEOHWKHFDSWXUHDQGPRQLWRULQJRIDQ\DFXWHDQGVXEDFXWHWR[LFLWLHV
3UHOLPLQDU\DVVHVVPHQWRIWKHVDIHW\RIWKHWUHDWPHQWUHJLPHQZLOORFFXUE\WKH1DQW.ZHVW6DIHW\
5HYLHZ&RPPLWWHH65&(QUROOPHQWLQWRWKHSKDVHESRUWLRQZLOOFRQWLQXHLIGDWDIURPWKHLQLWLDO
VXEMHFWVVXJJHVWWKDWWKHFRPELQDWLRQWKHUDS\LVWROHUDEOH
,QSKDVHVXEMHFWVZLOOEHHQUROOHGLQWRRIFRKRUWVVXEMHFWVZKRKDYHIDLOHGILUVWOLQH6R&
WKHUDS\ILUVWOLQHPHWDVWDWLFRUSURJUHVVHGDIWHUDGMXYDQWFKHPRWKHUDS\VSHFLILFDOO\LQFOXGLQJ
)2/),5,12;JHPFLWDELQHDQGQDESDFOLWD[HOJHPFLWDELQHDQGFDSHFLWDELQHRUJHPFLWDELQHDORQH
DQGVXEMHFWVZKRKDYHEHHQWUHDWHGZLWKPRUHWKDQRQHOLQHRI6R&WKHUDS\,QSKDVH255ZLOO
EHHYDOXDWHGVHSDUDWHO\IRUHDFKFRKRUWXVLQJ6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQ
7UHDWPHQWZLOOEHDGPLQLVWHUHGLQWZRSKDVHVDQLQGXFWLRQDQGDPDLQWHQDQFHSKDVHDVGHVFULEHG
EHORZ6XEMHFWVZLOOFRQWLQXHLQGXFWLRQWUHDWPHQWIRUXSWR\HDU7UHDWPHQWLQWKHVWXG\ZLOOEH
GLVFRQWLQXHGLIWKHVXEMHFWH[SHULHQFHVSURJUHVVLYHGLVHDVH3'RUXQDFFHSWDEOHWR[LFLW\QRW
FRUUHFWHGZLWKGRVHUHGXFWLRQZLWKGUDZVFRQVHQWRULIWKH,QYHVWLJDWRUIHHOVLWLVQRORQJHULQWKH
VXEMHFW¶VEHVWLQWHUHVWWRFRQWLQXHWUHDWPHQW7KRVHZKRKDYHDFRPSOHWHUHVSRQVH&5LQWKH
LQGXFWLRQSKDVHZLOOHQWHUWKHPDLQWHQDQFHSKDVHRIWKHVWXG\6XEMHFWVZKRH[SHULHQFHRQJRLQJ
VWDEOHGLVHDVH6'RUDQRQJRLQJSDUWLDOUHVSRQVH35DW\HDUPD\HQWHUWKHPDLQWHQDQFHSKDVHDW


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

WKH,QYHVWLJDWRU¶VGLVFUHWLRQ6XEMHFWVPD\UHPDLQRQWKHPDLQWHQDQFHSKDVHRIWKHVWXG\IRUXSWR
\HDU7UHDWPHQWZLOOFRQWLQXHLQWKHPDLQWHQDQFHSKDVHXQWLOWKHVXEMHFWH[SHULHQFHV3'RU
XQDFFHSWDEOHWR[LFLW\QRWFRUUHFWHGZLWKGRVHUHGXFWLRQZLWKGUDZVFRQVHQWRULIWKH,QYHVWLJDWRU
IHHOVLWLVQRORQJHULQWKHVXEMHFW¶VEHVWLQWHUHVWWRFRQWLQXHWUHDWPHQW7KHPD[LPXPWLPHRQVWXG\
WUHDWPHQWLQFOXGLQJERWKWKHLQGXFWLRQDQGPDLQWHQDQFHSKDVHVLV\HDUV
([SORUDWRU\WXPRUPROHFXODUSURILOLQJZLOOEHFRQGXFWHGRQVDPSOHVFROOHFWHGSULRUWRWUHDWPHQWRQ
WKLVVWXG\ZHHNVDIWHUWKHVWDUWRIWUHDWPHQWDQGGXULQJSRWHQWLDOSURORQJHGLQGXFWLRQDQG
PDLQWHQDQFHSKDVHVGHSHQGLQJRQUHVSRQVHDVGHVFULEHGLQ6HFWLRQ6HSDUDWHEORRGWXEHVZLOO
EHFROOHFWHGHYHU\ZHHNVLQWKHLQGXFWLRQSKDVHDQGHYHU\ZHHNVLQWKHPDLQWHQDQFHSKDVHGXULQJ
URXWLQHEORRGGUDZVIRUH[SORUDWRU\LPPXQRORJ\DQGFW'1$FW51$DQDO\VHVDVGHVFULEHGLQ
6HFWLRQDQG6HFWLRQUHVSHFWLYHO\
7XPRUVZLOOEHDVVHVVHGDWVFUHHQLQJDQGWXPRUUHVSRQVHZLOOEHDVVHVVHGHYHU\ZHHNVGXULQJWKH
LQGXFWLRQSKDVHDQGHYHU\ZHHNVGXULQJWKHPDLQWHQDQFHSKDVHE\FRPSXWHGWRPRJUDSK\&7
PDJQHWLFUHVRQDQFHLPDJLQJ05,RUSRVLWURQHPLVVLRQWRPRJUDSK\FRPSXWHGWRPRJUDSK\
3(7&7RIWDUJHWDQGQRQWDUJHWOHVLRQVLQDFFRUGDQFHZLWK5HVSRQVH(YDOXDWLRQ&ULWHULDLQ6ROLG
7XPRUV5(&,679HUVLRQDQGLPPXQHUHODWHGUHVSRQVHFULWHULDLU5&
Prospective Tumor Molecular Profiling
3URVSHFWLYHWXPRUPROHFXODUSURILOLQJZLOOEHFRQGXFWHGWRLQIRUPRASPXWDWLRQDOVWDWXVDQGZLOOEH
XVHGWRGHWHUPLQHZKHWKHU*,ZLOOEHDGPLQLVWHUHG*,DGPLQLVWUDWLRQZLOOEHLQLWLDWHGDV
VRRQDVUHVXOWVIURPWXPRUPROHFXODUSURILOLQJDUHDYDLODEOH$OOVXEMHFWVZLOOUHFHLYHDOORWKHUDJHQWV
UHJDUGOHVVRIWKHLUWXPRUPROHFXODUSURILOH
3URVSHFWLYHWXPRUPROHFXODUSURILOLQJZLOOEHSHUIRUPHGRQ))3(WXPRUWLVVXHDQGZKROHEORRG
VXEMHFWPDWFKHGQRUPDOFRPSDUDWRUDJDLQVWWKHWXPRUWLVVXHFROOHFWHGSULRUWRWUHDWPHQWRQWKLV
VWXG\7UHDWPHQWZLWKDOOVWXG\GUXJVH[FHSW*,PD\EHLQLWLDWHGEHIRUH))3(WXPRUWLVVXH
DQGRUUHVXOWVIURPSURVSHFWLYHWXPRUPROHFXODUSURILOLQJDUHDYDLODEOHLQWKHHYHQWWKDWWKLVRFFXUV
WUHDWPHQWRIVXEMHFWVZLWKWXPRUVSRVLWLYHIRUVSHFLILFRASPXWDWLRQVWDUJHWHGE\*,ZLOOEHJLQ
DVVRRQDVPROHFXODUSURILOLQJUHVXOWVDUHDYDLODEOH0RUHLQIRUPDWLRQRQWKHFROOHFWLRQRIWXPRU
WLVVXHDQGZKROHEORRGLVGHVFULEHGLQ6HFWLRQDQGLVVLPLODUWRWKHFROOHFWLRQRIVDPSOHVIRU
WKHH[SORUDWRU\WXPRUPROHFXODUSURILOLQJ
6XEMHFWVZLOOUHFHLYH*,LIWKHLUWXPRULVSRVLWLYHIRUVSHFLILFRASPXWDWLRQVDVGHWHUPLQHGE\
ZKROHJHQRPHVHTXHQFLQJ$VGHVFULEHGLQ6HFWLRQ*,LVVHSDUDWHSURGXFWVIURPWKH*,
VHULHV*,*,*,DQG*,HDFKRIWKHVHH[SUHVVHVDFRPELQDWLRQRI
PXWDWHG5$6RQFRSURWHLQV7KHVSHFLILFRASPXWDWLRQZLOOGHWHUPLQHZKLFK*,SURGXFWZLOOEH
XVHGIRUWUHDWPHQW*,IRU*9*,IRU*&*,IRU*'*,IRU*5RU
4+DQG*,*,RU*,IRU4/RU45
Induction Phase:
7KHLQGXFWLRQSKDVHZLOOFRQVLVWRIUHSHDWHGZHHNF\FOHVIRUDPD[LPXPWUHDWPHQWSHULRGRI\HDU
7KHWUHDWPHQWUHJLPHQRIDOGR[RUXELFLQ+&O$/7DYHOXPDEEHYDFL]XPDEF\FORSKRVSKDPLGH
$GEDVHGYDFFLQH(7%;)8OHXFRYRULQ\HDVWEDVHGYDFFLQH*,KD1.
QDESDFOLWD[HORPHJDDFLGHWK\OHVWHUVDQGR[DOLSODWLQZLOOEHUHSHDWHGHYHU\ZHHNV&RQFXUUHQW
6%57ZLOOEHJLYHQGXULQJWKHILUVWWZRZHHNF\FOHV5DGLDWLRQZLOOEHDGPLQLVWHUHGWRQRPRUH
WKDQWXPRUVLWHVXVLQJ6%57DVGHVFULEHGLQ6HFWLRQ
7KHLQGXFWLRQSKDVHRIVWXG\WUHDWPHQWZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKWKHIROORZLQJGRVLQJ
UHJLPHQ
'DLO\


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

•
2PHJDDFLGHWK\OHVWHUVJE\PRXWK>32@WZLFHDGD\>%,'@
'D\HYHU\ZHHNV
•
%HYDFL]XPDEPJNJ,9
'D\V±DQG±HYHU\ZHHNV
•
)8PJPFRQWLQXRXV,9LQIXVLRQRYHU±KRXUV
'D\V±±DQG±HYHU\ZHHNV
•
&\FORSKRVSKDPLGHPJ32%,'
'D\VDQGHYHU\ZHHNV
•
1DESDFOLWD[HOPJ,9
•
2[DOLSODWLQPJP,9
'D\VDQGHYHU\ZHHNV
•
/HXFRYRULQPJP,9EROXV
'D\HYHU\ZHHNVIRUF\FOHVWKHQHYHU\ZHHNVWKHUHDIWHU
•
(7%;îYLUXVSDUWLFOHV>93@YDFFLQHGRVHVXEFXWDQHRXVO\>6&@
'D\VDQGHYHU\ZHHNV
•
$OGR[RUXELFLQ+&OPJP,9RQGD\DQGPJP,9RQGD\
'D\VDQGHYHU\ZHHNV
•
6%57QRWWRH[FHHG*\H[DFWGRVHWREHGHWHUPLQHGE\WKHUDGLDWLRQRQFRORJLVWIRU
WKHILUVWF\FOHVRQO\
'D\HYHU\ZHHNV
•
$YHOXPDEPJNJ,9RYHUKRXU
'D\VDQGHYHU\ZHHNV
•
$/7ȝJNJ6&DWOHDVWPLQXWHVSULRUWRKD1.LQIXVLRQ
'D\VDQGHYHU\ZHHNV
•
KD1.îFHOOVGRVH,9
'D\HYHU\ZHHNVIRUF\FOHVDQGHYHU\ZHHNVWKHUHDIWHU
•
*,\HDVWXQLWV><8@GRVH6&
3URVSHFWLYHWXPRUPROHFXODUSURILOLQJZLOOGHWHUPLQHZKHWKHU*,ZLOOEH
DGPLQLVWHUHGDVGHVFULEHGDERYH*,DGPLQLVWUDWLRQZLOOEHLQLWLDWHGDVVRRQDV
UHVXOWVIURPWXPRUPROHFXODUSURILOLQJDUHDYDLODEOH
Maintenance Phase:
7KHGXUDWLRQRIWKHPDLQWHQDQFHSKDVHZLOOEHXSWR\HDUIROORZLQJFRPSOHWLRQRIWKHODVWWUHDWPHQW
LQWKHLQGXFWLRQSKDVH7KHGXUDWLRQRIWKHPDLQWHQDQFHSKDVHFDQH[FHHG\HDULIWKHVXEMHFW
FRQWLQXHVWREHQHILWSHUWKH,QYHVWLJDWRU¶VGLVFUHWLRQ7KHPDLQWHQDQFHSKDVHZLOOFRQVLVWRIUHSHDWHG


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

ZHHNF\FOHV7KHWUHDWPHQWUHJLPHQRIDOGR[RUXELFLQ+&O$/7DYHOXPDEEHYDFL]XPDE
F\FORSKRVSKDPLGHFDSHFLWDELQH$GEDVHGYDFFLQH(7%;\HDVWEDVHGYDFFLQH*,
KD1.QDESDFOLWD[HODQGRPHJDDFLGHWK\OHVWHUVZLOOEHUHSHDWHGHYHU\ZHHNV
7KHPDLQWHQDQFHSKDVHRIVWXG\WUHDWPHQWZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKWKHIROORZLQJGRVLQJ
UHJLPHQ
'DLO\
•
2PHJDDFLGHWK\OHVWHUVJ32%,'
'D\HYHU\ZHHNV
•
$OGR[RUXELFLQ+&OPJP,9
•
%HYDFL]XPDEPJNJ,9
•
1DESDFOLWD[HOPJ,9
'D\V±HYHU\ZHHNV
•
&DSHFLWDELQHPJP32%,'
'D\V±DQG±HYHU\ZHHNV
•
&\FORSKRVSKDPLGHPJ32%,'
'D\HYHU\ZHHNV
•
$/7JNJ6&DWOHDVWPLQXWHVSULRUWRKD1.LQIXVLRQ
•
$YHOXPDEPJNJ,9RYHUKRXU
•
KD1.îFHOOVGRVH,9
'D\HYHU\ZHHNVWKHUHDIWHU
•
(7%;î93GRVH6&
•
*,<8GRVH6&KRXUVDIWHUDGPLQLVWUDWLRQRIWKH$GEDVHGYDFFLQH
3URVSHFWLYHWXPRUPROHFXODUSURILOLQJZLOOGHWHUPLQHZKHWKHU*,ZLOOEH
DGPLQLVWHUHGDVGHVFULEHGDERYH


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

Phase 1b
Primary Endpoint:
•
,QFLGHQFHRIWUHDWPHQWHPHUJHQWDGYHUVHHYHQWV$(VDQGVHULRXV$(V6$(VJUDGHG
XVLQJWKH1DWLRQDO&DQFHU,QVWLWXWH1&,&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH
(YHQWV&7&$(9HUVLRQ
Secondary Endpoints:
•
255E\5(&,679HUVLRQ
•
255E\LU5&
•
3)6E\5(&,679HUVLRQ
•
3)6E\LU5&
•
26
•
'25E\5(&,679HUVLRQDQGLU5&
•
'&5FRQILUPHG&535RUVWDEOHGLVHDVH>6'@ODVWLQJIRUDWOHDVWPRQWKVE\5(&,67
DQGLU5&
•
4R/E\352V
Exploratory Endpoints:
•
7XPRUPROHFXODUSURILOHVDQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
•
7KHUDS\LQGXFHGFKDQJHVLQLPPXQHUHVSRQVHVDQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
•
0ROHFXODUFKDQJHVLQFW'1$DQGFW51$DQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
Phase 2
Primary Endpoint:
•
255E\5(&,679HUVLRQ
Secondary Endpoints:
•
255E\LU5&
•
3)6E\5(&,679HUVLRQ
•
3)6E\LU5&
•
26
•
'25E\5(&,679HUVLRQDQGLU5&
•
'&5FRQILUPHG&535RU6'ODVWLQJIRUDWOHDVWPRQWKVE\5(&,679HUVLRQ
DQGLU5&
•
4R/E\352V
•
,QFLGHQFHRIWUHDWPHQWHPHUJHQW$(V6$(VJUDGHGXVLQJWKH1&,&7&$(9HUVLRQ


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\


Exploratory Endpoints:
•
7XPRUPROHFXODUSURILOHVDQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
•
7KHUDS\LQGXFHGFKDQJHVLQLPPXQHUHVSRQVHVDQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
•
0ROHFXODUFKDQJHVLQFW'1$DQGFW51$DQGFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
Enrollment (planned):
,QWKHSKDVHESRUWLRQRIWKHVWXG\WRVXEMHFWVZLOOEHHQUROOHG7KHLQLWLDOVXEMHFWVZLOOEH
HQUROOHGLQDVWDJJHUHGIDVKLRQZLWKDGD\LQWHUYDOEHWZHHQHDFKVXEMHFW
,QWKHSKDVHSRUWLRQRIWKHVWXG\255ZLOOEHHYDOXDWHGVHSDUDWHO\XVLQJ6LPRQ¶VWZRVWDJH
RSWLPDOGHVLJQIRUFRKRUWVWKDWLQFOXGHVXEMHFWVZKRKDYHIDLOHGILUVWOLQH6R&WKHUDS\ILUVWOLQH
PHWDVWDWLFRUSURJUHVVHGDIWHUDGMXYDQWFKHPRWKHUDS\VSHFLILFDOO\LQFOXGLQJ)2/),5,12;
JHPFLWDELQHDQGQDESDFOLWD[HOJHPFLWDELQHDQGFDSHFLWDELQHRUJHPFLWDELQHDORQHDQGVXEMHFWV
ZKRKDYHEHHQWUHDWHGZLWKPRUHWKDQRQHOLQHRI6R&WKHUDS\
)RUFRKRUWVXEMHFWVZLOOEHHQUROOHGLQWKHILUVWVWDJHRI6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQ,IWKH
VWXG\SURFHHGVWRWKHVHFRQGVWDJHRI6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQDQDGGLWLRQDOVXEMHFWV
ZLOOEHHQUROOHGLQWKHVHFRQGVWDJHIRUDWRWDORIVXEMHFWVLQWKHSKDVHSRUWLRQRIWKHVWXG\IRU
FRKRUW
)RUFRKRUWVXEMHFWVZLOOEHHQUROOHGLQWKHILUVWVWDJHRI6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQ,IWKH
VWXG\SURFHHGVWRWKHVHFRQGVWDJHRI6LPRQ¶VWZRVWDJHRSWLPDOGHVLJQDQDGGLWLRQDOVXEMHFWV
ZLOOEHHQUROOHGLQWKHVHFRQGVWDJHIRUDWRWDORIVXEMHFWVLQWKHSKDVHSRUWLRQRIWKHVWXG\IRU
FRKRUW
7KHPD[LPXPWRWDOHQUROOPHQWIRUWKHVWXG\LVVXEMHFWV
Eligibility Criteria:
Inclusion Criteria:

$JH\HDUVROG

$EOHWRXQGHUVWDQGDQGSURYLGHDVLJQHGLQIRUPHGFRQVHQWWKDWIXOILOOVWKHUHOHYDQW,5%RU
,QGHSHQGHQW(WKLFV&RPPLWWHH,(&JXLGHOLQHV

+LVWRORJLFDOO\FRQILUPHGSDQFUHDWLFDGHQRFDUFLQRPDZLWKSURJUHVVLRQRQRUDIWHU6R&
WKHUDS\

(&2*SHUIRUPDQFHVWDWXVRIWR

+DYHDWOHDVWPHDVXUDEOHOHVLRQRIFP

0XVWKDYHDUHFHQWIRUPDOLQIL[HGSDUDIILQHPEHGGHG))3(WXPRUELRSV\VSHFLPHQ
IROORZLQJWKHFRQFOXVLRQRIWKHPRVWUHFHQWDQWLFDQFHUWUHDWPHQWDQGEHZLOOLQJWRUHOHDVHWKH
VSHFLPHQIRUSURVSHFWLYHDQGH[SORUDWRU\WXPRUPROHFXODUSURILOLQJ,IDQKLVWRULFVSHFLPHQ
LVQRWDYDLODEOHWKHVXEMHFWPXVWEHZLOOLQJWRXQGHUJRDELRSV\GXULQJWKHVFUHHQLQJSHULRG
LIFRQVLGHUHGVDIHE\WKH,QYHVWLJDWRU,IVDIHW\FRQFHUQVSUHFOXGHFROOHFWLRQRIDELRSV\
GXULQJWKHVFUHHQLQJSHULRGDWXPRUELRSV\VSHFLPHQFROOHFWHGSULRUWRWKHFRQFOXVLRQRIWKH
PRVWUHFHQWDQWLFDQFHUWUHDWPHQWPD\EHXVHG

0XVWEHZLOOLQJWRSURYLGHEORRGVDPSOHVSULRUWRWKHVWDUWRIWUHDWPHQWRQWKLVVWXG\IRU


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

SURVSHFWLYHWXPRUPROHFXODUSURILOLQJDQGH[SORUDWRU\DQDO\VHV

0XVWEHZLOOLQJWRSURYLGHDWXPRUELRSV\VSHFLPHQZHHNVDIWHUWKHVWDUWRIWUHDWPHQWIRU
H[SORUDWRU\DQDO\VHVLIFRQVLGHUHGVDIHE\WKH,QYHVWLJDWRU

$ELOLW\WRDWWHQGUHTXLUHGVWXG\YLVLWVDQGUHWXUQIRUDGHTXDWHIROORZXSDVUHTXLUHGE\WKLV
SURWRFRO
 $JUHHPHQWWRSUDFWLFHHIIHFWLYHFRQWUDFHSWLRQIRUIHPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDO
DQGQRQVWHULOHPDOHV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOPXVWDJUHHWRXVHHIIHFWLYH
FRQWUDFHSWLRQIRUXSWR\HDUDIWHUFRPSOHWLRQRIWKHUDS\DQGQRQVWHULOHPDOHVXEMHFWVPXVW
DJUHHWRXVHDFRQGRPIRUXSWRPRQWKVDIWHUWUHDWPHQW(IIHFWLYHFRQWUDFHSWLRQLQFOXGHV
VXUJLFDOVWHULOL]DWLRQHJYDVHFWRP\WXEDOOLJDWLRQWZRIRUPVRIEDUULHUPHWKRGVHJ
FRQGRPGLDSKUDJPXVHGZLWKVSHUPLFLGHLQWUDXWHULQHGHYLFHV,8'VDQGDEVWLQHQFH
Exclusion Criteria:

6HULRXVXQFRQWUROOHGFRQFRPLWDQWGLVHDVHWKDWZRXOGFRQWUDLQGLFDWHWKHXVHRIWKH
LQYHVWLJDWLRQDOGUXJXVHGLQWKLVVWXG\RUWKDWZRXOGSXWWKHVXEMHFWDWKLJKULVNIRUWUHDWPHQW
UHODWHGFRPSOLFDWLRQV

6\VWHPLFDXWRLPPXQHGLVHDVHHJOXSXVHU\WKHPDWRVXVUKHXPDWRLGDUWKULWLV$GGLVRQ
V
GLVHDVHDXWRLPPXQHGLVHDVHDVVRFLDWHGZLWKO\PSKRPD

+LVWRU\RIRUJDQWUDQVSODQWUHTXLULQJLPPXQRVXSSUHVVLRQ

+LVWRU\RIRUDFWLYHLQIODPPDWRU\ERZHOGLVHDVHHJ&URKQ
VGLVHDVHXOFHUDWLYHFROLWLV

,QDGHTXDWHRUJDQIXQFWLRQHYLGHQFHGE\WKHIROORZLQJODERUDWRU\UHVXOWV
D
$EVROXWHQHXWURSKLOFRXQWFHOOVPP
E
3ODWHOHWFRXQWFHOOVPP
F
7RWDOELOLUXELQJUHDWHUWKDQWZLFHWKHXSSHUOLPLWRIQRUPDO8/1XQOHVVWKHVXEMHFWKDV
GRFXPHQWHG*LOEHUW¶VV\QGURPH
G
$VSDUWDWHDPLQRWUDQVIHUDVH$67>6*27@RUDODQLQHDPLQRWUDQVIHUDVH$/7>6*37@
!î8/1!î8/1LQVXEMHFWVZLWKOLYHUPHWDVWDVHV
H
$ONDOLQHSKRVSKDWDVHOHYHOV!î8/1!î8/1LQVXEMHFWVZLWKOLYHUPHWDVWDVHV
RU!î8/1LQVXEMHFWVZLWKERQHPHWDVWDVHV
I
6HUXPFUHDWLQLQH!PJG/RUȝPRO/
J
6HUXPDQLRQJDS!P(T/RUDUWHULDOEORRGZLWKS+
K
0HGLFDOO\XQFRUUHFWDEOHJUDGHDQHPLDKHPRJORELQJG/

8QFRQWUROOHGK\SHUWHQVLRQV\VWROLF!PP+JDQGRUGLDVWROLF!PP+JRU
FOLQLFDOO\VLJQLILFDQWLHDFWLYHFDUGLRYDVFXODUGLVHDVHFHUHEURYDVFXODUDFFLGHQWVWURNHRU
P\RFDUGLDOLQIDUFWLRQZLWKLQPRQWKVSULRUWRILUVWVWXG\PHGLFDWLRQXQVWDEOHDQJLQD
FRQJHVWLYHKHDUWIDLOXUHRI1HZ<RUN+HDUW$VVRFLDWLRQJUDGHRUKLJKHURUVHULRXVFDUGLDF
DUUK\WKPLDUHTXLULQJPHGLFDWLRQ7RFRQWUROK\SHUWHQVLRQLWLVUHFRPPHQGHGWRILUVWVWDUW
SURSUDQRORO65PJGDLO\SULRUWRLQLWLDWLQJRWKHUK\SHUWHQVLYHPHGLFDWLRQV

6HULRXVP\RFDUGLDOG\VIXQFWLRQGHILQHGE\(&+2DVDEVROXWHOHIWYHQWULFXODUHMHFWLRQ
IUDFWLRQ/9()EHORZWKHLQVWLWXWLRQ¶VORZHUOLPLWRISUHGLFWHGQRUPDO

'\VSQHDDWUHVWGXHWRFRPSOLFDWLRQVRIDGYDQFHGPDOLJQDQF\RURWKHUGLVHDVHUHTXLULQJ


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

FRQWLQXRXVR[\JHQWKHUDS\

3RVLWLYHUHVXOWVRIVFUHHQLQJWHVWIRUKXPDQLPPXQRGHILFLHQF\YLUXV+,9
 &XUUHQWFKURQLFGDLO\WUHDWPHQWFRQWLQXRXVIRU!PRQWKVZLWKV\VWHPLFFRUWLFRVWHURLGV
GRVHHTXLYDOHQWWRRUJUHDWHUWKDQPJGD\PHWK\OSUHGQLVRORQHH[FOXGLQJLQKDOHG
VWHURLGV6KRUWWHUPVWHURLGXVHWRSUHYHQW,9FRQWUDVWDOOHUJLFUHDFWLRQRUDQDSK\OD[LVLQ
VXEMHFWVZKRKDYHNQRZQFRQWUDVWDOOHUJLHVLVDOORZHG
 .QRZQK\SHUVHQVLWLYLW\WRDQ\FRPSRQHQWRIWKHVWXG\PHGLFDWLRQV
 6XEMHFWVWDNLQJDQ\PHGLFDWLRQVKHUEDORUSUHVFULEHGNQRZQWRKDYHDQDGYHUVHGUXJ
UHDFWLRQZLWKDQ\RIWKHVWXG\PHGLFDWLRQV
 &RQFXUUHQWRUSULRUXVHRIDVWURQJF\WRFKURPH3&<3$LQKLELWRULQFOXGLQJ
NHWRFRQD]ROHLWUDFRQD]ROHSRVDFRQD]ROHFODULWKURP\FLQLQGLQDYLUQHID]RGRQHQHOILQDYLU
ULWRQDYLUVDTXLQDYLUWHOLWKURP\FLQYRULFRQD]ROHDQGJUDSHIUXLWSURGXFWVRUVWURQJ&<3$
LQGXFHUVLQFOXGLQJSKHQ\WRLQFDUEDPD]HSLQHULIDPSLQULIDEXWLQULIDSHQWLQSKHQREDUELWDO
DQG6W-RKQ
V:RUWZLWKLQGD\VEHIRUHVWXG\GD\
 &RQFXUUHQWRUSULRUXVHRIDVWURQJ&<3&LQKLELWRUJHPILEUR]LORUPRGHUDWH&<3&
LQGXFHUULIDPSLQZLWKLQGD\VEHIRUHVWXG\GD\
 3DUWLFLSDWLRQLQDQLQYHVWLJDWLRQDOGUXJVWXG\RUKLVWRU\RIUHFHLYLQJDQ\LQYHVWLJDWLRQDO
WUHDWPHQWZLWKLQGD\VSULRUWRLQLWLDWLRQRIWUHDWPHQWRQWKLVVWXG\H[FHSWIRUWHVWRVWHURQH
ORZHULQJWKHUDS\LQPHQZLWKSURVWDWHFDQFHU
 $VVHVVHGE\WKH,QYHVWLJDWRUWREHXQDEOHRUXQZLOOLQJWRFRPSO\ZLWKWKHUHTXLUHPHQWVRIWKH
SURWRFRO
 &RQFXUUHQWSDUWLFLSDWLRQLQDQ\LQWHUYHQWLRQDOFOLQLFDOWULDO
 3UHJQDQWDQGQXUVLQJZRPHQ
Products, Dosage, and Mode of Administration: 
Investigational Products
Dosage 
Mode of Administration
$OGR[RUXELFLQ+&O
PJPRUPJPLQGXFWLRQ
PJPPDLQWHQDQFH
,9
$/7
JNJ
6&
(7%;
î93GRVH
6&
*,
<8GRVH
6&
KD1.FHOOV
îFHOOVGRVH
,9
Approved Products
Dosage
Mode of Administration
$YHOXPDE
PJNJ
,9
%HYDFL]XPDE
PJNJ
,9
&DSHFLWDELQH
PJP
32%,'
&\FORSKRVSKDPLGH
PJ
32%,'


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

)8
PJP
KRXUWRKRXU
FRQWLQXRXV,9LQIXVLRQ
/HXFRYRULQ
PJP
,9EROXV
1DESDFOLWD[HO
PJLQGXFWLRQ
PJPDLQWHQDQFH
,9
2PHJDDFLGHWK\OHVWHUV
J
32%,'
2[DOLSODWLQ
PJP
,9
6%57
*\PD[LPXPH[DFWGRVHWREH
GHWHUPLQHGE\WKHUDGLDWLRQ
RQFRORJLVW
([WHUQDOEHDPUDGLDWLRQ
Duration of Treatment:
•
,QGXFWLRQSKDVHZHHNVPLQLPXPWR\HDUPD[LPXP
•
0DLQWHQDQFHSKDVH8SWR\HDU
6XEMHFWVZLOOEHWUHDWHGIRUXSWR\HDUVXSWR\HDULQHDFKWUHDWPHQWSKDVHRUXQWLOWKH\
H[SHULHQFHSURJUHVVLYHGLVHDVHXQDFFHSWDEOHWR[LFLW\QRWFRUUHFWHGZLWKGRVHUHGXFWLRQZLWKGUDZ
FRQVHQWRULIWKH,QYHVWLJDWRUIHHOVLWLVQRORQJHULQWKHLUEHVWLQWHUHVWWRFRQWLQXHWUHDWHPHQW
Duration of Follow-up: 
6XEMHFWVZKRGLVFRQWLQXHVWXG\WUHDWPHQWVKRXOGUHPDLQLQWKHVWXG\DQGFRQWLQXHWREHIROORZHG
HYHU\GD\VGD\VIRU
•
5HVROXWLRQRIDQ\6$(VDWWULEXWHGWRWUHDWPHQWVHH6HFWLRQ
•
&705,RU3(7&7VFDQDVVHVVPHQWVHH6HFWLRQ
•
9LWDOVWDWXVVXEMHFWVZLOOEHIROORZHGXQWLOHLWKHUGHDWKRUIRUDPLQLPXPRIPRQWKV
SDVWDGPLQLVWUDWLRQRIWKHILUVWGRVHRIFKHPRWKHUDS\WRWKHODVWVXEMHFWHQUROOHGLQWKH
VWXG\ZKLFKHYHUFRPHVILUVW
6XEMHFWVPD\FRQWLQXHWREHIROORZHGE\WKHLQYHVWLJDWLRQDOSK\VLFLDQRUDWKLUGSDUW\E\SKRQHRU
UHYLHZRIPHGLFDOUHFRUGVDSSUR[LPDWHO\HYHU\GD\VXQWLOZLWKGUDZDORIFRQVHQWORVWWRIROORZXS
RUGHDWKE\DQ\FDXVH$GGLWLRQDOLQIRUPDWLRQIURPDVXEMHFW¶VPHGLFDOUHFRUGVUHOHYDQWWRWKLV
VWXG\PD\EHSURYLGHGWR1DQW.ZHVWDVQHHGHGWRXQGHUVWDQGWKHVDIHW\DQGHIILFDF\RIWKHUHJLPHQ
WHVWHGLQWKLVSURWRFRO
Reference Therapy, Dosage, and Mode of Administration:
1RWDSSOLFDEOH


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW

&RQILGHQWLDODQG3URSULHWDU\

Evaluation of Endpoints:
Safety:
6DIHW\HQGSRLQWVLQFOXGHDVVHVVPHQWVRIWUHDWPHQWHPHUJHQW$(V6$(VDQGFOLQLFDOO\VLJQLILFDQW
FKDQJHVLQVDIHW\ODERUDWRU\WHVWVSK\VLFDOH[DPLQDWLRQVHOHFWURFDUGLRJUDPV(&*V
HFKRFDUGLRJUDPV(&+2VDQGYLWDOVLJQV$OOVXEMHFWVZLOOEHHYDOXDEOHIRUWR[LFLW\IURPWKHWLPH
RIWKHLUILUVWVWXG\WUHDWPHQW7R[LFLWLHVZLOOEHJUDGHGXVLQJWKH1&,&7&$(9HUVLRQ
Efficacy:
255DQG3)6ZLOOEHDVVHVVHGE\&7RIWDUJHWDQGQRQWDUJHWOHVLRQVHYHU\ZHHNVGXULQJWKH
LQGXFWLRQSKDVHDQGHYHU\ZHHNVGXULQJWKHPDLQWHQDQFHSKDVHDQGZLOOEHHYDOXDWHGLQ
DFFRUGDQFHZLWK5(&,679HUVLRQDQGLU5&26'25DQG'&5ZLOODOVREHDVVHVVHG
$QDVVHVVPHQWRI4R/ZLOOEHFRQGXFWHGYLD352VXVLQJWKH)XQFWLRQDO$VVHVVPHQWRI&DQFHU
7KHUDS\+HSDWRELOLDU\&DQFHU)$&7+HSLQVWUXPHQWRQVWXG\GD\HYHU\ZHHNVWKHUHDIWHU
GD\RIZHHNVHWFSULRUWRWUHDWPHQWGXULQJLQGXFWLRQSKDVHHYHU\ZHHNVGXULQJ
PDLQWHQDQFHDQGDWWKHHQGRIWUHDWPHQW(27YLVLW
Exploratory Analysis: 
Tumor Molecular Profiling: *HQRPLFVHTXHQFLQJRIWXPRUFHOOVIURPWLVVXHUHODWLYHWRQRQWXPRU
FHOOVIURPZKROHEORRGZLOOEHFRQGXFWHGWRLGHQWLI\WXPRUVSHFLILFJHQRPLFYDULDQFHVWKDWPD\
FRQWULEXWHWRGLVHDVHSURJUHVVLRQDQGRUUHVSRQVHWRWUHDWPHQW51$VHTXHQFLQJZLOOEHFRQGXFWHGWR
SURYLGHH[SUHVVLRQGDWDDQGJLYHUHOHYDQFHWR'1$PXWDWLRQV4XDQWLWDWLYHSURWHRPLFVDQDO\VLVZLOO
EHFRQGXFWHGWRGHWHUPLQHWKHDEVROXWHDPRXQWVRIVSHFLILFSURWHLQVWRFRQILUPH[SUHVVLRQRIJHQHV
WKDWDUHFRUUHODWLYHRIGLVHDVHSURJUHVVLRQDQGRUUHVSRQVHDQGWRGHWHUPLQHWKHFXWRIIYDOXHVIRU
UHVSRQVH
Immunologic Analysis: ,PPXQHUHVSRQVHVWRWKH1$17SDQFUHDWLFFDQFHUUHJLPHQZLOOEHHYDOXDWHG
E\VWDQGDUGLPPXQHDVVD\V&RUUHODWLRQVEHWZHHQWKHUDS\LQGXFHGLPPXQHFKDQJHVDQGVXEMHFW
RXWFRPHVZLOOEHDVVHVVHG
ctDNA/ctRNA AnalysisFW'1$DQGFW51$ZLOOEHH[WUDFWHGIURPSODVPDREWDLQHGIURPZKROH
EORRG([SUHVVLRQOHYHOVRIVSHFLILFWXPRUDQGLPPXQHUHODWHGDQDO\WHVZLOOEHDVVHVVHGE\
TXDQWLWDWLYHUHDOWLPHSRO\PHUDVHFKDLQUHDFWLRQT3&5DQGSRVVLEO\RWKHUPHWKRGVHJ'1$51$
VHTXHQFLQJDQGDQDO\]HGIRUFRUUHODWLRQVZLWKVXEMHFWRXWFRPHV
Statistical Methods:
7KLVSKDVHEVWXG\ZLOOH[DPLQHWKHRYHUDOOVDIHW\SURILOHDQGHIILFDF\RIPHWURQRPLFFRPELQDWLRQ
WKHUDS\LQVXEMHFWVZLWKSDQFUHDWLFFDQFHUZKRVHWXPRUVKDYHSURJUHVVHGRQRUDIWHU6R&WUHDWPHQW
6DIHW\UHVXOWVZLOOEHSUHVHQWHGVHSDUDWHO\IRUWKHLQGXFWLRQDQGPDLQWHQDQFHSKDVHVRIWUHDWPHQWDV
ZHOODVRYHUDOOIRUWKHHQWLUHWUHDWPHQWUHJLPHQ(IILFDF\UHVXOWVZLOOEHVXPPDUL]HGIRUWKHRYHUDOO
WUHDWPHQWUHJLPHQDQGSUHVHQWHGVHSDUDWHO\IRUFRKRUWVDQG
2YHUDOOVDIHW\ZLOOEHDVVHVVHGE\GHVFULSWLYHDQDO\VHVXVLQJWDEXODWHGIUHTXHQFLHVRI$(VE\JUDGH
XVLQJ&7&$(YHUVLRQLQWHUPVRIWUHDWPHQWHPHUJHQW$(V6$(VDQGFOLQLFDOO\VLJQLILFDQW
FKDQJHVLQVDIHW\ODERUDWRU\WHVWVSK\VLFDOH[DPLQDWLRQV(&*V(&+2VDQGYLWDOVLJQV
255ZLOOEHHYDOXDWHGLQDFFRUGDQFHZLWK5(&,679HUVLRQDQGLU5&7KHSHUFHQWDJHRIVXEMHFWV
DQGFRQILGHQFHLQWHUYDO>&,@ZKRDFKLHYHDFRQILUPHGUHVSRQVHZLOOEHVXPPDUL]HG'&5ZLOO
EHHYDOXDWHGVLPLODUWR2553)626DQG'25ZLOOEHDQDO\]HGXVLQJ.DSODQ0HLHUPHWKRGV
'HVFULSWLYHVWDWLVWLFVRI352VZLOOEHSUHVHQWHG
&RUUHODWLRQVRIWXPRUPROHFXODUSURILOHVWKHUDS\LQGXFHGFKDQJHVLQLPPXQHUHVSRQVHVDQG
PROHFXODUFKDQJHVLQFW'1$DQGFW51$ZLWKVXEMHFWRXWFRPHVZLOOEHH[SORUHG


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW
&RQILGHQWLDODQG3URSULHWDU\

Figure 1: 
Study Treatment Schema


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW
&RQILGHQWLDODQG3URSULHWDU\

Figure 2: 
Induction Phase Treatment Schema


1$173DQFUHDWLF&DQFHU9DFFLQH
1DQW.ZHVW,QF
&OLQLFDO7ULDO3URWRFRO48,/7$PHQGPHQW
&RQILGHQWLDODQG3URSULHWDU\

Figure 3: 
Maintenance Phase Treatment Schema