Clinical trial NCT03387111
Conditions: Squamous Cell Carcinoma
Sponsor: ImmunityBio, Inc.
Start date: 2018-01-09; Completion date: 2021-01-11
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 SCC who have progressed on or after previous platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. Phase 2 will be based on Simon's two-stage optimal design.

Detailed description:
Treatment will be administered in 2 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 and Sponsor's discretion. Subjects may remain in the maintenance phase of the study for up to 1 year. The duration of the maintenance phase can exceed 1 year if the subject continues to benefit, per the Investigator's and Sponsor's discretion. 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 time on study treatment, including both the induction and maintenance phases, is up to 2 years. The duration of the study may exceed 2 years if the subject remains in the maintenance phase for more than 1 year, as described above.

Arms: arm 1: Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
Interventions: intervention 1: Aldoxorubicin HCl intervention 2: ETBX-011 intervention 3: ETBX-021 intervention 4: ETBX-051 intervention 5: ETBX-061 intervention 6: GI-4000 intervention 7: GI-6207 intervention 8: GI-6301 intervention 9: haNK for infusion intervention 10: Avelumab intervention 11: bevacizumab intervention 12: Capecitabine intervention 13: Cetuximab intervention 14: Cisplatin intervention 15: Cyclophosphamide intervention 16: Fluorouracil intervention 17: Leucovorin intervention 18: nab-Paclitaxel intervention 19: Necitumumab intervention 20: SBRT intervention 21: N-803
Intervention descriptions: intervention 1: Aldoxorubicin hydrochloride intervention 2: Ad5 \[E1-, E2b-\]-CEA intervention 3: Ad5 \[E1-, E2b-\]-HER2 intervention 4: Ad5 \[E1-, E2b-\]-Brachyury vaccine intervention 5: Ad5 \[E1-, E2b-\]-MUC1 intervention 6: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins intervention 7: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins intervention 8: Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins intervention 9: NK-92 \[CD16.158V, ER IL-2\] intervention 10: Recombinant human anti-PD-L1 IgG1 monoclonal antibody intervention 11: Recombinant human anti-VEGF IgG1 monoclonal intervention 12: 5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine intervention 13: Cetuximab is an epidermal growth factor receptor (EGFR) antagonist. intervention 14: cis-diamminedichloroplatinum(II) intervention 15: 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate intervention 16: 5-fluoro-2,4 (1H,3H)-pyrimidinedione intervention 17: 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 18: 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 19: Necitumumab is a recombinant human lgG1 monoclonal antibody. intervention 20: Stereotactic Body Radiation Therapy intervention 21: Recombinant human superagonist interleukin-15 (IL-15) complex \[also known as IL-15N72D:IL-15RuSu/IgGI Fe complex1)

Protocol documents:
Prot_SAP_000.pdf: 
NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
Confidential and Proprietary 
1 
 TITLE PAGE 
NANT SQUAMOUS CELL CARCINOMA (SCC) 
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 SCC WHO HAVE PROGRESSED 
ON OR AFTER PLATINUM-BASED CHEMOTHERAPY 
AND ANTI-PROGRAMMED CELL DEATH PROTEIN 1 
(PD-1)/PROGRAMMED DEATH-LIGAND 1 (PD-L1) 
THERAPY 
Study Number: 
QUILT-3.090 
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 
20 November 2017 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products: 
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human 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-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine) 
5. ETBX-051 (Ad5 [E1-, E2b-]-brachyury vaccine) 
6. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
7. GI-4000 (Ras yeast vaccine) 
8. GI-6207 (CEA yeast vaccine) 
9. GI-6301 (Brachyury yeast vaccine)  
10. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for IV use) 
12. Bevacizumab (AVASTIN® solution for IV infusion) 
13. Capecitabine (XELODA® tablets, for oral use) 
14. Cetuximab (ERBITUX® injection, for IV infusion) 
15. Cisplatin (CISplatin injection) 
16. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
17. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
18. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
19. Nab-paclitaxel  (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
20. Necitumumab (Portrazza® injection) 
21. Omega-3-acid ethyl esters (LOVAZA® Capsules, for oral use) 
22. Stereotactic body radiation therapy (SBRT) 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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Name of Active Ingredients: 
Investigational Products 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human super agonist interleukin-15 (IL-15) complex (also known as 
IL 15N72D:IL-15RαSu/IgG1 Fc complex)  
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-HER2 
5. Ad5 [E1-, E2b-]-Brachyury 
6. Ad5 [E1-, E2b-]-MUC1  
7. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L) 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
8. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
9. Recombinant yeast based vaccine expressing the human brachyury oncoprotein  
10. NK92 [CD16.158V, ER IL2] cells 
Approved Products 
11. Avelumab 
12. Bevacizumab 
13. Capecitabine 
14. Cetuximab 
15. Cisplatin  
16. Cyclophosphamide (anhydrous) 
17. Fluorouracil, USP 
18. Leucovorin (calcium salt) 
19. Paclitaxel, USP 
20. Necitumumab 
21. Omega-3-acid ethyl esters 
22. Radiation 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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Title of Study: 
NANT Squamous Cell Carcinoma (SCC) 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 SCC who have progressed on or after 
platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed death-
ligand 1 (PD-L1) therapy. 
Study Number: 
QUILT-3.090 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design) 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT SCC vaccine 
regimen in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 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 SCC vaccine regimen as 
assessed by ORR. 
• 
Secondary objectives are to determine 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 SCC who have progressed on or after previous platinum-based chemotherapy and anti-
PD-1/PD-L1 therapy. Phase 2 will be based on Simon’s two-stage optimal design. 
Preliminary assessment of the safety of the treatment regimen will occur by the NantKwest Safety 
Review Committee (SRC). Enrollment into the phase 1b portion will continue if data from the initial 
3 subjects suggest that the combination therapy is tolerable. 
Treatment will be administered in 2 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 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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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 and Sponsor’s discretion. Subjects may remain in the maintenance phase of the 
study for up to 1 year. The duration of the maintenance phase can exceed 1 year if the subject 
continues to benefit, per the Investigator’s and Sponsor’s discretion. 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 time on study treatment, including both the induction and maintenance 
phases, is up to 2 years. The duration of the study may exceed 2 years if the subject remains in the 
maintenance phase for more than 1 year, as described above. 
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 HER2 expression and RAS 
mutational status and will be used to determine whether ETBX-021 and GI-4000 will be 
administered. ETBX-021 and 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 ETBX-021 and 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 HER2 expression or specific RAS mutations 
with ETBX-021 and GI-4000, respectively, will begin as soon as tumor 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 ETBX-021 if their tumor overexpresses HER2 (≥ 750 attomole/µg of tumor 
tissue, as determined by quantitative proteomics with mass spectrometry). Subjects will receive 
GI-4000 if their tumor is positive for specific RAS mutations, as determined by whole genome 
sequencing. As described in Section 1.5.14.1, 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).  
 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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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, cetuximab or 
necitumumab, cisplatin, cyclophosphamide, Ad5-based vaccines (ETBX-011, ETBX-021, 
ETBX-051, and ETBX-061), 5-FU/leucovorin, yeast-based vaccines (GI-4000, GI-6207, and 
GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated every 3 weeks. 
Concurrent SBRT will be given during the first two 3-week cycles. Radiation will be administered to 
no more than 5 tumor sites using SBRT, as described in Section 5.1.5.1. 
The induction phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (by mouth [PO] twice per 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 (1,500 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) 
• 
Cisplatin (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, ETBX-021, ETBX-051, and ETBX-061 (1 × 1011 virus particles 
[VP]/vaccine/dose subcutaneously [SC]) 
Prospective tumor molecular profiling will determine whether ETBX-021 will be 
administered, as described above. 
Days 8 and 15: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist), 
every 3 weeks for 2 cycles 
• 
Aldoxorubicin HCl (80 mg/m2 IV on day 8 and 30 mg/m2 IV on day 15) , every 3 weeks 
 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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Days 8 and 16, every 3 weeks:  
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab 
will be administered to subjects with squamous non-small cell lung cancer. 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV over 1 hour) 
Days 9 and 16, every 3 weeks:  
• 
ALT-803 (10 μg/kg SC 30 minutes prior to haNK infusion) 
Days 9, 11, 16, and 18, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV) 
Day 11, every 3 weeks for 3 cycles and every 8 weeks thereafter: 
• 
GI-4000, GI-6207, GI-6301, (40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
 
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 from treatment, per the Investigator’s and Sponsor’s discretion. The maintenance 
phase will consist of repeated 2-week cycles. The treatment regimen of aldoxorubicin HCl, ALT-803, 
avelumab, bevacizumab, capecitabine, cetuximab or necitumumab, cyclophosphamide, Ad5-based 
vaccines (ETBX-011, ETBX-021, ETBX-051, and ETBX-061), yeast-based vaccines (GI-4000, GI-
6207, and GI-6301), haNK cells, nab-paclitaxel, and omega-3-acid ethyl esters will be repeated every 
2 weeks. 
The maintenance phase of study treatment will be conducted in accordance with the following dosing 
regimen: 
Daily:  
• 
Omega-3-acid ethyl esters (PO BID [3 × 1 g capsules and 2 × 1 g capsules]) 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Bevacizumab (5 mg/kg IV) 
• 
Nab-paclitaxel (100 mg IV) 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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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:  
• 
Avelumab (10 mg/kg IV over 1 hour) 
• 
Cetuximab (250 mg/m2 IV) 
OR  
necitumumab (400 mg IV) 
• 
ALT-803 (10 µg/kg SC) (30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with HNSCC, while necitumumab will be administered to subjects with 
squamous NSCLC. 
Day 5, every 8 weeks thereafter: 
• 
ETBX-011, ETBX-021, ETBX-051, ETBX-061 (1 × 1011 VP/vaccine/dose SC) 
• 
GI-4000, GI-6207, GI-6301 (40 YU/vaccine/dose SC), 2 hours after administration of 
Ad-5 based vaccines 
Prospective tumor molecular profiling will determine whether ETBX-021 and GI-4000 
will be administered, as described above. 
 
 
Phase 1b 
Primary Endpoints: 
• 
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. 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1 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 and SAEs, graded using the NCI CTCAE 
Version 4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. In the phase 2 portion of the 
study, 21 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 20 subjects will be 
enrolled in the second stage, for a total of 41 subjects in the phase 2 portion of the study. The 
maximum total enrollment in the study is 65 subjects. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after 
platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
5. Have at least 1 measurable lesion of ≥ 1.5 cm. 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anticancer treatment and be willing to release the 
specimen for prospective and exploratory tumor molecular profiling. If an historic specimen 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 
10. Agreement to practice effective contraception for female subjects of child-bearing potential 
and non-sterile males. Female subjects of child-bearing potential must agree to use effective 
contraception for up to 1 year after completion of therapy, and non-sterile male subjects must 
agree to use a condom for up to 4 months after treatment. Effective contraception includes 
surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, 
condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence. 
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, or 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. 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 
 
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6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or 
clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or 
myocardial infarction within 6 months prior to first study medication; unstable angina; 
congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac 
arrhythmia requiring medication. To control hypertension it is recommended to first start 
propranolol SR 80 mg daily prior to initiating other hypertensive medications. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection 
fraction (LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids 
(dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled 
steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in 
subjects who have known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, 
and St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 
inducer (rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational 
treatment within 14 days prior to screening for this study, except for testosterone-lowering 
therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 


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Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2  or 30 mg/m2 
(induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
1 × 1011 VP/dose  
SC 
ETBX-021 
1 × 1011 VP/dose  
SC 
ETBX-051 
1 × 1011 VP/dose  
SC 
ETBX-061 
1 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
GI-6207 
40 YU/dose 
SC 
GI-6301 
40 YU/dose 
SC 
haNK  
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 
Cetuximab 
250 mg/m2 
IV 
Cisplatin 
40 mg/m2 
IV 
Cyclophosphamide  
50 mg 
PO BID 
5-FU 
1500 mg/m2  
85- to 96-hour continuous IV 
infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (induction);  
100 mg (maintenance) 
IV 
Necitumumab 
400 mg 
IV 
Omega-3-acid ethyl esters 
5 g 
PO 
SBRT 
8 Gy maximum (exact dose to 
be determined by the radiation 
oncologist) 
External beam radiation 


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Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum) 
• 
Maintenance phase: Up to 1 year.  The duration of the maintenance phase can exceed 
1 year if the subject continues to benefit, per the Investigator’s and Sponsor’s discretion. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they 
experience PD, unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if 
the Investigator feels it is no longer in their best interest to continue treatment. The duration of the 
study can exceed 2 years if the subject continues to benefit and the maintenance phase is extended, 
per the Investigator’s and Sponsor’s discretion. 
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. 


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Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT, MRI, or PET-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-Head and Neck (FACT-H&N) or Functional Assessment of Cancer Therapy-Lung 
(FACT-L) instruments 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 Analyses: 
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 SCC vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 therapy. 
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 


NANT Squamous Cell Carcinoma Vaccine 
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Figure 1: 
Study Treatment Schema 
 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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Figure 2: 
Induction Phase Treatment Schema 
 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 
 
Confidential and Proprietary 
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Figure 3: 
Maintenance Phase Treatment Schema 
 


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


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)a 
 
 
Study Week 
 
1 
2 
3 
EOT 
Visitb 
Unscheduled 
Visitc 
Study Day 
-28 to -1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
 
 
Laboratory Assessments 
Chemistry panelj 
X 
Xk 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Hematologyl 
X 
X
k 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Urinalysis 
X 
X
k 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Pregnancy testm 
X 
X
k 
Every 6 weeks 
X 
 
Serum virology (HIV)n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine HER2 expression 
and RAS mutational statuso 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for tumor 
molecular profilingp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect whole blood for 
ctDNA/ctRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
 
 
 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
 
 
Additional tumor biopsy 
 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
 
 
Tumor Imaging and Assessments 
CT, MRI, or PET-CTs
 
X 
Every 8 weeks 
X 
 
 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction phase until the subject experiences PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to continue 
treatment. Those who have a CR in the induction phase will enter the maintenance phase of the study. 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 and Sponsor’s discretion. 
b End-of-treatment visit must be performed 30 (±5 days) after the last study treatment. 


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c Additional assessments performed during an unscheduled visit are at the discretion of the Investigator or treating physician and must be recorded in the 
subject’s source documents and on the Unscheduled Visit eCRF. 
d Inclusion/exclusion criteria will also be evaluated at enrollment. 
e Medical history will also be evaluated at enrollment. 
f Subject’s FFPE tumor tissue sample must be obtained following the conclusion of the most recent anticancer treatment and prior to first study treatment. If not 
available, a fresh tumor biopsy must be performed, if considered safe by the Investigator. In the event a fresh biopsy needs to be scheduled, the site may 
consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to the first dose of any study 
drug. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most 
recent anticancer treatment may be used. Treatment on this study may be initiated before FFPE tumor tissue and/or results from prospective tumor molecular 
profiling are available; in the event that this occurs, treatment of subjects with tumors positive for HER2 expression or specific RAS mutations targeted by 
GI-4000 will begin as soon as molecular profiling results are available. 
g Height required at screening visit only. 
h Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vitals signs are to be obtained after the subject has 
been in a seated resting position for at least 5 minutes and within 30 minutes prior to the start of any infusional study treatment. For visits where a subject is 
receiving an infusion of any study compounds, vital signs will be collected at the following time points in relation to the start of first infusion of the day: prior 
to infusion, 15 minutes post, 30 minutes post, 1 hour post, 2 hours post, 3 hours post, 4 hours post, 5 hours post, 6 hours post, 7 hours post, and 8 hours post 
infusion. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if clinically indicated. 
i 12-lead ECG to be performed in triplicate at screening. 
j Chemistry panel to include laboratory assessments noted in Table 17.  
k Day 1 assessments can be skipped if the screening assessment was performed within 1 week prior to the start of treatment. 
l Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
m Serum pregnancy test at screening; urine dipstick pregnancy test for all other tests (for females of child-bearing potential). 
n HIV status to be determined by ELISA and confirmed by western blot. 
o Assessment of HER2 expression to determine whether ETBX-021 will be administered to the subject and assessment of RAS mutational status to determine 
whether GI-4000 will be administered to the subject, as described in Section 3.1.1. Treatment on this study may be initiated before FFPE tumor tissue and/or 
results from prospective tumor molecular profiling are available; in the event that this occurs, treatment of subjects with tumors positive for HER2 expression 
or specific RAS mutations targeted by GI-4000 will begin as soon as molecular profiling results are available. 
p Whole blood for tumor molecular profiling will be collected during the screening period for subjects who have been enrolled in the study. 
q Whole blood for immunology and ctDNA/ctRNA analyses will be collected during the screening period for subjects who have been enrolled in the study, every 
6 weeks in the induction phase during routine blood draws, and at the EOT visit. 
r Historic tumor biopsy specimen for tumor molecular profiling is required to determine eligibility for participation in the study. If an historic specimen is not 
available, a fresh tumor biopsy must be performed, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening 
period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used. In the event a fresh biopsy needs to be 
scheduled, the site may consent the subject and schedule the screening visit assessments to be performed such that all assessments fall within 28 days prior to 
the first dose of any study medications. A tumor biopsy is also required 8 weeks after the start of treatment, if considered safe by the Investigator. 


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s Tumor imaging by CT scan, MRI, or PET-CT will be performed at screening and every 8 weeks thereafter in the induction phase. Evaluations may include CT, 
MRI, or PET-CT scans of the chest, abdomen, pelvis (optional unless known pelvic disease is present at screening), and brain (only as clinically warranted 
based on symptoms/findings). All screening tumor imaging assessments should be performed based on the subject's qualifying scan obtained within 28 days 
prior to the start of treatment. RECIST and irRC documentation are to be completed at each assessment period. The same mode of imaging is required to be 
carried through each subject’s respective treatment period. 


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Table 19: 
Schedule of Events for Maintenance Phase of Study 
 
 
Maintenance Phase Treatment (repeats every 2 weeks, except where noted)a 
 
 
Study Week 
1 
2 
EOT Visitb 
Unscheduled 
Visitc 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
 
Concomitant medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Physical exam, weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signsd 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
ECOG performance status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
12-lead ECG 
X 
Every 12 weeks 
X 
 
ECHO (with ejection 
fraction) 
X 
Every 12 weeks 
X 
 
Confirm contraceptive 
measures 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event collection 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
FACT-H&N or FACT-L 
questionnaire 
X 
Every 12 weeks 
X 
 
Laboratory Assessments 
Chemistry panele 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Hematologyf 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Pregnancy testg 
X 
Every 12 weeks 
X 
 
Collect whole blood for 
immunology analysish 
X 
Every 8 weeks during routine blood draws 
X 
 
Collect whole blood for 
ctDNA/ctRNA analysish 
X 
Every 8 weeks during routine blood draws 
X 
 


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Maintenance Phase Treatment (repeats every 2 weeks, except where noted)a 
 
 
Study Week 
1 
2 
EOT Visitb 
Unscheduled 
Visitc 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion 
 CT, MRI, or PET-CTi 
X 
Every 12 weeks 
X 
 
a Subjects will remain in the maintenance phase of the study for up to 1 year. The duration of the maintenance phase can exceed 1 year if the subject continues to 
benefit, per the Investigator’s and Sponsor’s discretion. 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. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vitals signs are to be obtained after the subject has 
been in a seated resting position for at least 5 minutes. For visits where a subject is receiving an infusion of any study compounds, vital signs will be collected 
at the following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, 1 hour post, 2 hours post, 3 
hours post, 4 hours post, 5 hours post, 6 hours post, 7 hours post, and 8 hours post infusion. Temperature will be documented each visit at the first pre-infusion 
assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Urine dipstick pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and ctDNA/ctRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT scan, MRI, or PET-CT will be performed every 12 weeks in the maintenance phase. Evaluations may include CT, MRI, or PET-CT 
scans of the chest, abdomen, pelvis (optional unless known pelvic disease is present at screening), and brain (only as clinically warranted based on 
symptoms/findings). RECIST and irRC documentation to be completed at each assessment period. The same mode of imaging is required to be carried through 
each subject’s respective treatment period. 


NANT Squamous Cell Carcinoma Vaccine 
Clinical Trial Protocol: QUIL T-3 .090 
APPENDIX 1. SPONSOR SIGNATURE 
NantKwest, Inc. 
Study Title: 
NANT Squamous Cell Carcinoma (SCC) 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 
sec who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein I 
(PD- I )/programmed death-ligand I (PD-LI) therapy. 
Study Number: 
QUILT-3.090 
Version Number: 
1.0 
Final Date: 
20November2017 
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: 
. /~~ 
~e<J·:--·· -------- - <4~ ~ 
,,. 
John H.-'Lee, MD 
Seni6; Vice President Adult Medical Affairs, 
NflhtK west Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
Confidential and Proprietary 
172 
Date: ;!/;[/ 2 I )()Ir 


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NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
Confidential and Proprietary 
1 
 TITLE PAGE 
NANT SQUAMOUS CELL CARCINOMA (SCC) 
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 SCC WHO HAVE PROGRESSED 
ON OR AFTER PLATINUM-BASED CHEMOTHERAPY 
AND ANTI-PROGRAMMED CELL DEATH PROTEIN 1 
(PD-1)/PROGRAMMED DEATH-LIGAND 1 (PD-L1) 
THERAPY 
Study Number: 
QUILT-3.090 
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 
20 November 2017 
Version 2 
27 December 2017 
Version 3 
27 February 2018 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 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-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine) 
5. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
6. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
7. GI-4000 (Ras yeast vaccine) 
8. GI-6207 (CEA yeast vaccine) 
9. GI-6301 (Brachyury yeast vaccine)  
10. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
1. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
2. Bevacizumab (AVASTIN® solution for IV infusion) 
3. Capecitabine (XELODA® tablets, for oral use) 
4. Cetuximab (ERBITUX® injection, for IV infusion) 
5. Cisplatin (CISplatin injection) 
6. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
7. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
8. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
9. Nab-paclitaxel  (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
10. Necitumumab (Portrazza® injection) 
11. Stereotactic body radiation therapy (SBRT) 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 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. Ad5 [E1-, E2b-]-HER2 
5. Ad5 [E1-, E2b-]-Brachyury 
6. Ad5 [E1-, E2b-]-MUC1  
7. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L) 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
8. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
9. Recombinant yeast based vaccine expressing the human brachyury oncoprotein  
10. NK92 [CD16.158V, ER IL2] cells 
Approved Products 
1. Avelumab 
2. Bevacizumab 
3. Capecitabine 
4. Cetuximab 
5. Cisplatin  
6. Cyclophosphamide (anhydrous) 
7. Fluorouracil, USP 
8. Leucovorin (calcium salt) 
9. Paclitaxel, USP 
10. Necitumumab 
11. Radiation 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
5 
Title of Study: 
NANT Squamous Cell Carcinoma (SCC) 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 SCC who have progressed on or after 
platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed 
death-ligand 1 (PD-L1) therapy. 
Study Number: 
QUILT-3.090 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design) 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT SCC vaccine 
regimen in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 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 SCC vaccine regimen as 
assessed by ORR using RECIST Version 1.1 based on Blinded Independent Central 
Review (BICR). 
• 
Secondary objectives are to determine 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 SCC who have progressed on or after previous platinum-based chemotherapy and anti-
PD-1/PD-L1 therapy. Phase 2 will be based on Simon’s two-stage optimal design. 
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 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
6 
3 subjects suggest that the combination therapy is tolerable. 
Treatment will be administered in 2 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 and Sponsor’s discretion. Subjects may remain in 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 time on study 
treatment, including both the induction and maintenance phases, is up to 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 HER2 expression and RAS 
mutational status and will be used to determine whether ETBX-021 and GI-4000 will be 
administered. ETBX-021 and 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 ETBX-021 if their tumor overexpresses HER2 (≥ 750 attomole/µg of tumor 
tissue, as determined by quantitative proteomics with mass spectrometry). 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: 
 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
7 
Day 1, every 3 weeks:  
• 
Bevacizumab (5 mg/kg IV) 
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV over 1 hour) 
Days 1–5, every 3 weeks: 
• 
5-FU (1,500 mg/m2 continuous IV infusion over 85–96 hours) 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
ETBX-011, ETBX-021, ETBX-051, and ETBX-061 (1 × 1011 virus particles 
[VP]/vaccine/dose subcutaneously [SC]) 
Prospective tumor molecular profiling will determine whether ETBX-021 will be 
administered, as described above. 
Day 8 
• 
Aldoxorubicin HCl (80 mg/m2 IV over 30 minutes)  
• 
Cisplatin (20 mg/m2 IV over 1 hour) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab 
will be administered to subjects with squamous non-small cell lung cancer (NSCLC). 
Days 8–12, every 3 weeks: 
• 
 Cyclophosphamide (25 mg PO daily [QD]) 
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) 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
8 
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter: 
• 
GI-4000, GI-6207, GI-6301, (40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 will be 
administered, as described above. 
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) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab 
will be administered to subjects with squamous non-small cell lung cancer (NSCLC).  
Day 18, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV)  
 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles, as follows: 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV over 30 minutes) 
• 
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:  
• 
Avelumab (10 mg/kg IV over 1 hour) 
• 
Cetuximab (250 mg/m2 IV) 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
9 
OR  
necitumumab (400 mg IV) 
• 
ALT-803 (10 µg/kg SC) (at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with HNSCC, while necitumumab will be administered to subjects with 
squamous NSCLC. 
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
ETBX-011, ETBX-021, ETBX-051, ETBX-061 (1 × 1011 VP/vaccine/dose SC) 
• 
GI-4000, GI-6207, GI-6301 (40 YU/vaccine/dose SC), 2 hours after administration of 
Ad-5 based vaccines 
Prospective tumor molecular profiling will determine whether ETBX-021 and GI-4000 
will be administered, as described above. 
Phase 1b 
Primary Endpoints: 
• 
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded 
using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.03. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
 
 


NANT Squamous Cell Carcinoma Vaccine 
NantKwest, Inc. 
Clinical Trial Protocol: QUILT-3.090 Amendment 2 
 
Confidential and Proprietary 
10 
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 and SAEs, graded using the NCI CTCAE 
Version 4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by the Investigator; in the phase 2 
portion of the study, the primary assessment of response will be assessed on BICR. A charter for the 
conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 21 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 20 subjects 
will be enrolled in the second stage, for a total of 41 subjects in the phase 2 portion of the study. The 
maximum total enrollment in the study is 65 subjects. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after 
platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. 


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4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
5. Have at least 1 measurable lesion of ≥ 1.0 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anticancer treatment and be willing to release the 
specimen for prospective and exploratory tumor molecular profiling. If an historic specimen 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 
10. Agreement to practice effective contraception for female subjects of child-bearing potential 
and non-sterile males. Female subjects of child-bearing potential must agree to use effective 
contraception for up to 1 year after completion of therapy, and non-sterile male subjects must 
agree to use a condom for up to 4 months after treatment. Effective contraception includes 
surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, 
condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence. 
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, or 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. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
c. Platelet count < 75,000 cells/mm3. 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 
or >10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3. 


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6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or 
clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or 
myocardial infarction within 6 months prior to first study medication; unstable angina; 
congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac 
arrhythmia requiring medication. Subjects with uncontrolled hypertension should be 
medically managed on a stable regimen to control hypertension prior to study entry. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection 
fraction (LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids 
(dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled 
steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in 
subjects who have known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, 
and St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 
inducer (rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational 
treatment within 30 days prior to screening for this study, except for testosterone-lowering 
therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 


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Products, Dosage, and Mode of Administration: 
Investigational Products Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ALT-803 
10 µg/kg  
SC 
ETBX-011 
1 × 1011 VP/dose  
SC 
ETBX-021 
1 × 1011 VP/dose  
SC 
ETBX-051 
1 × 1011 VP/dose  
SC 
ETBX-061 
1 × 1011 VP/dose  
SC 
GI-4000 
40 YU/dose 
SC 
GI-6207 
40 YU/dose 
SC 
GI-6301 
40 YU/dose 
SC 
haNK  
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID 
PO 
Cetuximab 
250 mg/m2 
IV 
Cisplatin 
40 mg/m2 (day 1) or 20 mg/m2 (day 8) 
IV 
Cyclophosphamide  
25 mg BID (days 1-5 of induction);  
25 mg once daily (days 8-12 of induction); 
25 mg BID (maintenance) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous 
IV infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (induction);  
100 mg (maintenance) 
IV 
Necitumumab 
400 mg 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation oncologist) 
External beam radiation 


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Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum) 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they 
experience PD, unacceptable toxicity (not correctable 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. 


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Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT, MRI, or PET-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-Head and Neck (FACT-H&N) or Functional Assessment of Cancer Therapy-Lung 
(FACT-L) instruments 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 Analyses: 
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 SCC vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 therapy. Safety results will be presented separately for the 
induction and maintenance phases of treatment as well as overall for the entire treatment regimen. 
Efficacy results will be summarized for the overall treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR.  
PFS, OS, and DOR will be analyzed using Kaplan-Meier methods.  
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 


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Figure 1: 
Study Treatment Schema 
 


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Figure 2: 
Induction Phase Treatment Schema 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 


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


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)a 
 
 
Study Week 
 
1 
2 
3 
EOT 
Visitb 
Unscheduled 
Visitc 
Study Day 
-28 to -1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
 
 
Laboratory Assessments 
Chemistry panelk 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Hematologyl 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Urinalysis 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Pregnancy testm 
X 
Xj 
Every 6 weeks 
X 
 
Serum virology (HIV)n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine HER2 expression 
and RAS mutational statuso 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for tumor 
molecular profilingp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect whole blood for 
ctDNA/ctRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
 
 
 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
 
 
Additional tumor biopsy 
 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
 
 
Tumor Imaging and Assessments 
CT, MRI, or PET-CTs
 
X 
Every 8 weeks 
X 
 
 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction phase until the subject experiences PD or 
unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to continue 
treatment. Those who have a CR in the induction phase will enter the maintenance phase of the study. 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 and Sponsor’s discretion. Any required laboratory sample 
collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 


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


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s Tumor imaging by CT scan, MRI, or PET-CT will be performed at screening and every 8 weeks during the induction phase, as described in Section 6. All 
screening tumor imaging assessments should be performed based on the subject's qualifying scan obtained within 28 days prior to the start of treatment. 
RECIST and irRC documentation are to be completed at each assessment period.  


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


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Maintenance Phase Treatment (repeats every 2 weeks, except where noted)a 
 
 
Study Week 
1 
2 
EOT Visitb 
Unscheduled 
Visitc 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
 
 CT, MRI, or PET-CTi 
X 
Every 12 weeks 
X 
 
a Subjects will remain in the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Any required laboratory sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes. For visits where a subject is receiving an infusion of any study compounds, vital signs will be collected at the 
following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is 
discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and ctDNA/ctRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT scan, MRI, or PET-CT will be performed every 12 weeks in the maintenance phase, as described in Section 6. RECIST and irRC 
documentation to be completed at each assessment period. The same mode of imaging is required to be carried through each subject’s respective treatment 
period. 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 Amendment 2 
APPENDIX 1. SPONSOR SIGNATURE 
Study Title: 
NANT Squamous Cell Carcinoma (SCC) 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 
sec who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein 1 
(PD-1)/programmed death-ligand 1 (PD-Ll) therapy. 
Study Number: 
QUIL T-3.090 
Version Number: 
3 
Final Date: 
27 February 2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
H.Lee,MD 
enior Vice President Adult Medical Affairs, 
NantK west Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-6391 
Confidential and Proprietary 
173 
Date kb 2T /()I 8 


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 TITLE PAGE 
NANT SQUAMOUS CELL CARCINOMA (SCC) 
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 SCC WHO HAVE 
PROGRESSED ON OR AFTER PLATINUM-BASED 
CHEMOTHERAPY AND ANTI-PROGRAMMED CELL 
DEATH PROTEIN 1 (PD-1)/PROGRAMMED DEATH-
LIGAND 1 (PD-L1) THERAPY 
Study Number: 
QUILT-3.090 
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 
20 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
06 July 2018 


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


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products: 
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human superagonist interleukin-15 (IL-15) complex [also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] 
vaccine) 
4. ETBX-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine) 
5. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
6. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
7. GI-4000 (Ras yeast vaccine) 
8. GI-6207 (CEA yeast vaccine) 
9. GI-6301 (Brachyury yeast vaccine)  
10. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
1. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
2. Bevacizumab (AVASTIN® solution for IV infusion) 
3. Capecitabine (XELODA® tablets, for oral use) 
4. Cetuximab (ERBITUX® injection, for IV infusion) 
5. Cisplatin (CISplatin injection) 
6. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide 
Tablets, USP) 
7. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
8. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
9. Nab-paclitaxel  (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles 
for injectable suspension] [albumin-bound]) 
10. Necitumumab (Portrazza® injection) 
11. Stereotactic body radiation therapy (SBRT) 


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Name of Active Ingredients: 
Investigational Products 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex)  
3. Ad5 [E1-, E2b-]-CEA 
4. Ad5 [E1-, E2b-]-HER2 
5. Ad5 [E1-, E2b-]-Brachyury 
6. Ad5 [E1-, E2b-]-MUC1  
7. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L) 
and GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and 
Q61H) 
8. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
9. Recombinant yeast based vaccine expressing the human brachyury oncoprotein  
10. NK92 [CD16.158V, ER IL2] cells 
Approved Products 
1. Avelumab 
2. Bevacizumab 
3. Capecitabine 
4. Cetuximab 
5. Cisplatin  
6. Cyclophosphamide (anhydrous) 
7. Fluorouracil, USP 
8. Leucovorin (calcium salt) 
9. Paclitaxel, USP 
10. Necitumumab 
11. Radiation 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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Title of Study: 
NANT Squamous Cell Carcinoma (SCC) 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 SCC who have progressed on or after 
platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed 
death-ligand 1 (PD-L1) therapy. 
Study Number: 
QUILT-3.090 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design) 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT SCC Vaccine 
regimen in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 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 SCC Vaccine regimen as 
assessed by ORR using Response Evaluation Criteria in Solid Tumors (RECIST) Version 
1.1 based on Blinded Independent Central Review (BICR). 
• 
Secondary objectives are to determine additional measures of safety and efficacy (ORR 
by immune-related response criteria (irRC), 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 SCC who have progressed on or after previous platinum-based chemotherapy and anti-
PD-1/PD-L1 therapy. Phase 2 will be based on Simon’s two-stage optimal design. 
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 


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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3 subjects suggest that the combination therapy is tolerable. 
Treatment will be administered in 2 phases, an induction and a maintenance phase, as described 
below. Subjects will continue induction treatment for up to 1 year. 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 and Sponsor’s discretion. Subjects may remain in the 
maintenance phase of the study for up to 1 year.  
Treatment in the study will be discontinued if the subject experiences confirmed progressive disease 
(PD) or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the 
Investigator feels it is no longer in the subject’s best interest to continue treatment. Subjects with an 
initial assessment of PD per RECIST Version 1.1 may, at the discretion of the Investigator, continue 
to receive study treatment until PD is confirmed as detailed in Section 6.1.2. The time on study 
treatment, including both the induction and maintenance phases, is up to 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 until progression occurs by 
computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in 
accordance with RECIST Version 1.1 and irRC. The same mode(s) of assessment used to 
identify/evaluate lesions at screening should be used throughout the course of the study unless subject 
safety necessitates a change (eg, allergic reaction to contrast media). Unscheduled tumor assessments 
should be carried out if the investigator observes any signs or symptoms of PD. When disease 
progression per RECIST Version 1.1 is initially observed, experimental treatment may continue and 
an imaging assessment should be done 4–6 weeks after the initial PD assessment to rule out tumor 
pseudoprogression. If pseudoprogression is observed, the subject is allowed to continue experimental 
treatment and response assessments will continue every 8 or 12 weeks and will be evaluated per irRC. 
For subjects exhibiting a response (PR or CR), a confirmatory imaging assessment should be done 
4-6 weeks after the initial response.  
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood 
(subject-matched normal comparator against the tumor tissue) collected prior to treatment on this 
study. 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. 
Prospective tumor molecular profiling will be conducted to inform HER2 expression and RAS 
mutational status and will be used to determine whether ETBX-021 (HER2) and GI-4000 (RAS) will 
be administered. ETBX-021 (HER2) and GI-4000 (RAS) 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. 
Subjects will receive ETBX-021 (HER2) if their tumor is HER2-positive (IHC 3+ or FISH positive), 
as determined by an FDA-approved test. Subjects will receive GI-4000 (RAS) 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 


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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period of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
• 
Bevacizumab (5 mg/kg IV) 
Day 1, every 3 weeks:  
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (40 mg/m2 IV over approximately 1 hour) 
Days 1–5, every 3 weeks: 
• 
5-FU (1,500 mg/m2 continuous IV infusion over 85–96 hours) 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter:   
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), 
and ETBX-061 (MUC1) (1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) will be 
administered, as described above. 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (80 mg/m2 IV over approximately 30 minutes)  
• 
Cisplatin (20 mg/m2 IV over approximately 1 hour) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab 
will be administered to subjects with squamous non-small cell lung cancer (NSCLC). 
Days 8–12, every 3 weeks: 
• 
 Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
ALT-803 (15 μg/kg SC at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV) 
• 
Avelumab (10 mg/kg IV over approximately 1 hour)  


NANT Squamous Cell Carcinoma Vaccine 
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Day 11, every 3 weeks:  
• 
haNK (2 × 109 cells/dose IV) 
Day 11, every 3 weeks for 3 cycles and every 9 weeks thereafter: 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), GI-6301 (Brachyury) (40 yeast 
units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be 
administered, as described above. 
Day 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
the first 2 cycles only) 
Day 16, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with HNSCC, while necitumumab will be administered to subjects with 
squamous NSCLC.  
Day 18, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV)  
 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment 
in the induction phase. The maintenance phase will consist of repeated 2-week cycles, as follows: 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV over approximately 30 minutes) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID; up to a maximum of 1,000 mg per dose) 
• 
Cyclophosphamide (25 mg PO BID) 
Day 2, every 2 weeks:  
• 
ALT-803 (15 µg/kg SC) (at least 30 minutes prior to haNK infusion) 
• 
haNK (2 × 109 cells/dose IV) 


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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• 
Avelumab (10 mg/kg IV over approximately 1 hour) 
• 
Cetuximab (250 mg/m2 IV) 
OR  
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered 
to subjects with HNSCC, while necitumumab will be administered to subjects with 
squamous NSCLC. 
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), 
ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), GI-6301 (Brachyury) (40 
YU/vaccine/dose SC), approximately 2 hours after administration of Ad-5 based vaccines 
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) and 
GI-4000 (RAS) will be administered, as described above. 
Days 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Phase 1b 
Primary Endpoint: 
• 
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded 
using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.03. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
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• 
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 and SAEs, graded using the NCI CTCAE 
Version 4.03.  
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in 
the phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter 
for the conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of 
the study, 21 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 20 subjects 
will be enrolled in the second stage, for a total of 41 subjects in the phase 2 portion of the study. The 
maximum total enrollment in the study is 65 subjects. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 


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3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after 
platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
5. Have at least 1 measurable lesion of ≥ 1.0 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen 
following the conclusion of the most recent anticancer treatment and be willing to release the 
specimen for prospective and exploratory tumor molecular profiling. If an historic specimen 
is not available, the subject must be willing to undergo a biopsy during the screening period, 
if considered safe by the Investigator. If safety concerns preclude collection of a biopsy 
during the screening period, a tumor biopsy specimen collected prior to the conclusion of the 
most recent anticancer treatment may be used. 
7. Must be willing to provide blood samples prior to the start of treatment on this study for 
prospective tumor molecular profiling and exploratory analyses. 
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for 
exploratory analyses, if considered safe by the Investigator. 
9. Ability to attend required study visits and return for adequate follow-up, as required by this 
protocol. 
10. Agreement to practice effective contraception for female subjects of child-bearing potential 
and non-sterile males. Female subjects of child-bearing potential must agree to use effective 
contraception for up to 1 year after completion of therapy, and non-sterile male subjects must 
agree to use a condom for up to 4 months after treatment. Effective contraception includes 
surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, 
condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence. 
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, or 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. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
c. Platelet count < 75,000 cells/mm3. 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, 


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Clinical Trial Protocol: QUILT-3.090 Amendment 3 
 
Confidential and Proprietary 
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or >10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3. 
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or 
clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or 
myocardial infarction within 6 months prior to first study medication; unstable angina; 
congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac 
arrhythmia requiring medication. Subjects with uncontrolled hypertension should be 
medically managed on a stable regimen to control hypertension prior to study entry. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection 
fraction (LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids 
(dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled 
steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in 
subjects who have known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug 
reaction with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, 
and St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 
inducer (rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational 
treatment within 30 days prior to screening for this study, except for testosterone-lowering 
therapy in men with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 


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Products, Dosage, and Mode of Administration: 
Investigational Products Dosage 
Mode of Administration 
Aldoxorubicin HCl 
80 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV over approximately 30 
minutes 
ALT-803 
15 µg/kg  
SC 
ETBX-011 (CEA) 
1 × 1011 VP/dose  
SC 
ETBX-021 (HER2) 
1 × 1011 VP/dose  
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose  
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose  
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK  
2 × 109 cells/dose  
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV over approximately 1 
hour 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID up to a maximum of  
1,000 mg per dose 
PO 
Cetuximab 
250 mg/m2 
IV 
Cisplatin 
40 mg/m2 (day 1 of induction) or 20 mg/m2 
(day 8 of induction) 
IV over approximately 1 
hour 
Cyclophosphamide  
25 mg BID (days 1-5);  
25 mg once daily (days 8-12) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous 
IV infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (induction);  
100 mg (maintenance) 
IV 
Necitumumab 
400 mg 
IV 
SBRT 
8 Gy maximum (exact dose to be 
determined by the radiation oncologist) 
External beam radiation 


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Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum) 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they 
experience confirmed PD, unacceptable toxicity (not correctable 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 
until either death (any cause) or 24 months past administration of the first IP, whichever comes first, 
as follows: 
• 
Resolution of any SAEs attributed to treatment (see Section 7) 
• 
CT or MRI scan assessment (see Section 6.1.2) 
• 
Vital status: subjects will be followed until either death or for a minimum of 24 months 
past administration of the first dose of IP. 
Following documented PD, 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. 


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Evaluation of Endpoints: 
Safety:  
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), 
echocardiograms (ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time 
of their first study treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT or MRI of target and non-target lesions every 8 weeks during 
the induction phase and every 12 weeks during the maintenance phase and will be evaluated in 
accordance with RECIST Version 1.1 and irRC. 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 – 6 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 a local independent radiologist; in 
the phase 2 portion of the study, the primary assessment of response will be based on BICR. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer 
Therapy-Head and Neck (FACT-H&N) or Functional Assessment of Cancer Therapy-Lung 
(FACT-L) instruments 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 Analyses: 
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 SCC Vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject 
outcomes will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole 
blood. Expression levels of specific tumor- and immune-related analytes will be assessed by 
quantitative real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA 
sequencing) and analyzed for correlations with subject outcomes. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with SCC who have progressed on or after platinum-based 
chemotherapy and anti-PD-1/PD-L1 therapy.  
Safety results will be presented separately for the induction and maintenance phases of treatment as 
well as overall for the entire treatment regimen. Efficacy results will be summarized for the overall 
treatment regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade 
using CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will 
be evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods.  
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and 
molecular changes in ctDNA and ctRNA with subject outcomes will be explored. 


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Figure 1: 
Study Treatment Schema 
 


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Figure 2: 
Induction Phase Treatment Schema 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 


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


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)a 
 
 
Study Week 
 
1 
2 
3 
EOT 
Visitb 
Unscheduled 
Visitc 
Study Day 
-28 to -1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
 
 
Laboratory Assessments 
Chemistry panelk 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Hematologyl 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Urinalysis 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Pregnancy testm 
X 
Xj 
Every 6 weeks 
X 
 
Serum virology (HIV)n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine HER2 expression 
and RAS mutational statuso 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for tumor 
molecular profilingp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect whole blood for 
ctDNA/ctRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
 
 
 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
 
 
Additional tumor biopsy 
 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
 
 
Tumor Imaging and Assessments 
CT or MRIs
 
X 
Every 8 weeks 
X 
 
 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction phase until the subject experiences confirmed 
PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Those who have a CR in the induction phase will enter the maintenance phase of the study. 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 and Sponsor’s discretion. Any required laboratory 
sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 


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


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s Tumor imaging by CT scan or MRI will be performed at screening and every 8 weeks during the induction phase, as described in Section 6. All screening tumor 
imaging assessments should be performed based on the subject's qualifying scan obtained within 28 days prior to the start of treatment. RECIST and irRC 
documentation are to be completed at each assessment period.  


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


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Maintenance Phase Treatment (repeats every 2 weeks, except where noted)a 
 
 
Study Week 
1 
2 
EOT Visitb 
Unscheduled 
Visitc 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
 
 CT or MRIi 
X 
Every 12 weeks 
X 
 
a Subjects will remain in the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Any required laboratory sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes. For visits where a subject is receiving an infusion of any study compounds, vital signs will be collected at the 
following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is 
discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and ctDNA/ctRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT scan or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6. RECIST and irRC documentation to 
be completed at each assessment period. The same mode of imaging is required to be carried through each subject’s respective treatment period. 


NANT Squamous Cell Carcinoma Vaccine 
NantK west, Inc. 
Clinical Trial Protocol: QUIL T-3.090 Amendment 3 
APPENDIX 1. SPONSOR SIGNATURE 
Study Title: 
NANT Squamous Cell Carcinoma (SCC) 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 
sec who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein I 
(PD-1 )/programmed death-ligand I (PD-L 1) therapy. 
Study Number: 
QUTLT-3.090 
Version Number: 
4 
Final Date: 
06 July 2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The fol lowing personnel contributed to writing and/or approving this protocol: 
~ 
Signed:<._______ 
oatt:lu,{j /Q )-cJ I 8 
John H. 
e, MD 
ice President Adult Medical Affairs, 
tKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone: + 1-605-610-6391 
Confidential and Proprietary 
173 


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NANT SQUAMOUS CELL CARCINOMA (SCC) 
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 SCC WHO HAVE 
PROGRESSED ON OR AFTER PLATINUM-BASED 
CHEMOTHERAPY AND ANTI-PROGRAMMED CELL 
DEATH PROTEIN 1 (PD-1)/PROGRAMMED DEATH- 
LIGAND 1 (PD-L1) THERAPY 
Study Number: 
QUILT-3.090 
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 
20 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
06 July 2018 
Version 5 
01 August 2018 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products: 
1. Aldoxorubicin hydrochloride (HCl) 
2. ALT-803 (recombinant human superagonist interleukin-15 (IL-15) complex [also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex]) 
3. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine) 
4. ETBX-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine) 
5. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
6. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine) 
7. GI-4000 (Ras yeast vaccine) 
8. GI-6207 (CEA yeast vaccine) 
9. GI-6301 (Brachyury yeast vaccine) 
10. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
12. Bevacizumab (AVASTIN® solution for IV infusion) 
13. Capecitabine (XELODA® tablets, for oral use) 
14. Cetuximab (ERBITUX® injection, for IV infusion) 
15. Cisplatin (CISplatin injection) 
16. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide Tablets, 
USP) 
17. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
18. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
19. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles for 
injectable suspension] [albumin-bound]) 
20. Necitumumab (Portrazza® injection) 
21. Stereotactic body radiation therapy (SBRT) 


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Name of Active Ingredients: 
Investigational Products 
1. Aldoxorubicin HCl 
2. ALT-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex) 
3.  Ad5 [E1-, E2b-]-CEA 
4.  Ad5 [E1-, E2b-]-HER2 
5.   Ad5 [E1-, E2b-]-Brachyury 
6.  Ad5 [E1-, E2b-]-MUC1 
7. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L) and 
GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and Q61H) 
8. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
9. Recombinant yeast based vaccine expressing the human brachyury oncoprotein 
10. NK92 [CD16.158V, ER IL2] cells 
Approved Products 
11. Avelumab 
12. Bevacizumab 
13. Capecitabine 
14. Cetuximab 
15. Cisplatin 
16. Cyclophosphamide (anhydrous) 
17. Fluorouracil, USP 
18. Leucovorin (calcium salt) 
19. Paclitaxel, USP 
20. Necitumumab 
21. Radiation 


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Title of Study: 
NANT Squamous Cell Carcinoma (SCC) 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 SCC who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) 
therapy. 
Study Number: 
QUILT-3.090 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design) 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT SCC Vaccine 
regimen in subjects with SCC who have progressed on or after platinum-based chemotherapy 
and anti-PD-1/PD-L1 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 SCC Vaccine regimen as 
assessed by ORR using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 
based on Blinded Independent Central Review (BICR). 
• 
Secondary objectives are to determine additional measures of safety and efficacy (ORR by 
immune-related response criteria (irRC), 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 SCC who have progressed on or after previous platinum-based chemotherapy and 
anti-PD-1/PD-L1 therapy. Phase 2 will be based on Simon’s two-stage optimal design. 
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 


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the combination therapy is tolerable. 
Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. 
Subjects will continue induction treatment for up to 1 year. 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 and Sponsor’s discretion. Subjects may remain in the maintenance phase of the study for up 
to 1 year. 
Treatment in the study will be discontinued if the subject experiences confirmed progressive disease (PD) 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 
feels it is no longer in the subject’s best interest to continue treatment. Subjects with an initial assessment 
of PD per RECIST Version 1.1 may, at the discretion of the Investigator, continue to receive study 
treatment until PD is confirmed as detailed in Section 6.1.2. The time on study treatment, including both 
the induction and maintenance phases, is up to 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 until progression occurs by computed 
tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance 
with RECIST Version 1.1 and irRC. The same mode(s) of assessment used to identify/evaluate lesions at 
screening should be used throughout the course of the study unless subject safety necessitates a change 
(eg, allergic reaction to contrast media). Unscheduled tumor assessments should be carried out if the 
investigator observes any signs or symptoms of PD. When disease progression per RECIST Version 1.1 is 
initially observed, experimental treatment may continue and an imaging assessment should be done 
4-6 weeks after the initial PD assessment to rule out tumor pseudoprogression. If pseudoprogression is 
observed, the subject is allowed to continue experimental treatment and response assessments will 
continue every 8 or 12 weeks and will be evaluated per irRC. For subjects exhibiting a response (PR or 
CR), a confirmatory imaging assessment should be done 
4–6 weeks after the initial response. 
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood (subject- 
matched normal comparator against the tumor tissue) collected prior to treatment on this study. 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. 
Prospective tumor molecular profiling will be conducted to inform HER2 expression and RAS mutational 
status and will be used to determine whether ETBX-021 (HER2) and GI-4000 (RAS) will be 
administered. ETBX-021 (HER2) and GI-4000 (RAS) administration will be initiated as soon as results 
from tumor molecular profiling are available. All subjects will receive other agents regardless of their 
tumor molecular profile. 
Subjects will receive ETBX-021 (HER2) if their tumor is HER2-positive (IHC 3+ or FISH positive), as 
determined by an FDA-approved test. Subjects will receive GI-4000 (RAS) if their tumor is positive for 
specific RAS mutations, as determined by whole genome sequencing. 


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Induction Phase: 
Treatment in the induction phase will consist of repeated 3-week cycles for a maximum treatment period 
of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
• 
Bevacizumab (5 mg/kg IV) 
Day 1, every 3 weeks: 
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
• 
Cisplatin (32 mg/m2 IV) 
Days 1–5, every 3 weeks: 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and 
ETBX-061 (MUC1) (1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury) 
(40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) and 
GI-4000 (RAS) will be administered, as described above. 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (100 mg/m2 IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
≤ 4 cycles) 
Days 8–12, every 3 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
ALT-803 (15 μg/kg SC) 
• 
haNK (2 × 109 cells/dose IV) 
• 
Avelumab (10 mg/kg IV) 
Day 11, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV) 
• 
Cetuximab (250 mg/m2 IV) 
OR 


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necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab 
will be administered to subjects with squamous non-small cell lung cancer (NSCLC). 
Day 15, every 3 weeks: 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for ≤ 4 
cycles) 
• 
Nab-paclitaxel (100 mg IV) 
Day 16, every 3 weeks: 
• 
haNK (2 × 109 cells/dose IV) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with HNSCC, while necitumumab will be administered to subjects with squamous 
NSCLC. 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment in 
the induction phase. The maintenance phase will consist of repeated 2-week cycles, as follows: 
Day 1, every 2 weeks: 
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Days 1, 3, and 5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID; up to a maximum of 1,000 mg per dose) 
Day 2, every 2 weeks: 
• 
ALT-803 (15 µg/kg SC) 
• 
haNK (2 × 109 cells/dose IV) 
• 
Avelumab (10 mg/kg IV) 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 


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Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with HNSCC, while necitumumab will be administered to subjects with squamous 
NSCLC. 
Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and 
ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury) 
(40 YU/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether ETBX-021 (HER2) and 
GI-4000 (RAS) will be administered, as described above. 
Days 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
 
Phase 1b 
Primary Endpoint: 
• 
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.03. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 


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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 and SAEs, graded using the NCI CTCAE Version 4.03. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in ctDNA and ctRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter for the 
conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. The initial 3 subjects will be 
enrolled in a staggered fashion, with a 21-day interval between each subject. In the phase 2 portion of the 
study, 21 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 20 subjects will be 
enrolled in the second stage, for a total of 41 subjects in the phase 2 portion of the study. The maximum 
total enrollment in the study is 65 subjects. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after platinum- 
based chemotherapy and anti-PD-1/PD-L1 therapy. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 


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5. Have at least 1 measurable lesion of ≥ 1.0 cm. 
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following 
the conclusion of the most recent anticancer treatment and be willing to release the specimen for 
prospective and exploratory tumor molecular profiling. If an historic specimen is not available, 
the subject must be willing to undergo a biopsy during the screening period, if considered safe by 
the Investigator. If safety concerns preclude collection of a biopsy during 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, 
or 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. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
c. Platelet count < 75,000 cells/mm3. 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or 
>10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3. 


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6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically 
significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial 
infarction within 6 months prior to first study medication; unstable angina; congestive heart 
failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring 
medication. Subjects with uncontrolled hypertension should be medically managed on a stable 
regimen to control hypertension prior to study entry. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) 10% below the institution’s lower limit of predicted normal. 
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose 
equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. 
Short term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have 
known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction 
with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and 
St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer 
(rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational treatment 
within 30 days prior to screening for this study, except for testosterone-lowering therapy in men 
with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 


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Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
100 mg/m2 (induction); 
60 mg/m2 (maintenance) 
IV 
ALT-803 
15 µg/kg 
SC 
ETBX-011 (CEA) 
1 × 1011 VP/dose 
SC 
ETBX-021 (HER2) 
1 × 1011 VP/dose 
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose 
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose 
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK 
2 × 109 cells/dose 
IV 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID up to a maximum of 
1,000 mg per dose 
PO 
Cetuximab 
250 mg/m2 
IV 
Cisplatin 
32 mg/m2 
IV 
Cyclophosphamide 
25 mg BID (days 1-5); 
25 mg once daily (days 8-12) 
PO 
5-FU 
1500 mg/m2 
85- to 96-hour continuous 
IV infusion 
Leucovorin 
20 mg/m2 
IV bolus 
Nab-paclitaxel 
125 mg (day 1 of induction); 100 mg (day 15 
of induction and day 1 of maintenance) 
IV 
Necitumumab 
400 mg 
IV 
SBRT 
8 Gy maximum (exact dose to be determined 
by the radiation oncologist) 
External beam radiation 


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Duration of Treatment: 
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum) 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they experience 
confirmed PD, unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the 
Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up: 
Subjects who discontinue study treatment should remain in the study and continue to be followed for: 
• 
CT or MRI imaging and response assessments (see Section 6.1.2) 
• 
Collection of vital status every 90 days (± 14 days). 
Subjects should be followed until either death (any cause) or for a minimum of 24 months past 
administration of the first dose of study drug. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 


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Evaluation of Endpoints: 
Safety: 
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time of their first study 
treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT or MRI of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in accordance 
with RECIST Version 1.1 and irRC. 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 4–6 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 a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer Therapy- 
Head and Neck (FACT-H&N) or Functional Assessment of Cancer Therapy-Lung (FACT-L) instruments 
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 Analyses: 
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 SCC Vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject outcomes 
will be assessed. 
ctDNA/ctRNA Analysis: ctDNA and ctRNA will be extracted from plasma obtained from whole blood. 
Expression levels of specific tumor- and immune-related analytes will be assessed by quantitative 
real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA sequencing) and 
analyzed for correlations with subject outcomes. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with SCC who have progressed on or after platinum-based chemotherapy 
and anti-PD-1/PD-L1 therapy. 
Safety results will be presented separately for the induction and maintenance phases of treatment as well 
as overall for the entire treatment regimen. Efficacy results will be summarized for the overall treatment 
regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade using 
CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant changes in 
safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will be 
evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods. 
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and molecular 
changes in ctDNA and ctRNA with subject outcomes will be explored. 


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Figure 1: 
Study Treatment Schema 
 
 


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Figure 2: 
Induction Phase Treatment Schema 
 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 
 


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


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a
 
Study Week 
1 
2 
3 
EOT 
Visit
b
 
Unscheduled 
Visit
c
 
Study Day 
-28 to -1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Laboratory Assessments 
Chemistry panelk 
X 
Xj 
X 
X 
X 
Hematologyl 
X 
Xj 
X 
X 
X 
Urinalysis 
X 
Xj 
X 
X 
X 
Pregnancy testm 
X 
Xj 
Every 6 weeks 
X 
Serum virology (HIV)n 
X 
Determine HER2 expression 
and RAS mutational statuso 
X 
Collect whole blood for tumor 
molecular profilingp 
X 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect whole blood for 
ctDNA/ctRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
Additional tumor biopsy 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
Tumor Imaging and Assessments 
CT or MRIs 
X 
Every 8 weeks 
X 
 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction phase until the subject experiences confirmed 
PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Those who have a CR in the induction phase will enter the maintenance phase of the study. 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 and Sponsor’s discretion. Any required laboratory 
sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 


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


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s Tumor imaging by CT scan or MRI will be performed at screening and every 8 weeks during the induction phase, as described in Section 6. All screening tumor 
imaging assessments should be performed based on the subject's qualifying scan obtained within 28 days prior to the start of treatment. RECIST and irRC 
documentation are to be completed at each assessment period. 


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


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a 
Maintenance Phase Treatment (repeats every 2 weeks, except where noted) 
Study Week 
1 
2 
b 
EOT Visit 
Unscheduled 
c 
Visit 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
i 
CT or MRI 
X 
Every 12 weeks 
X 
a  Subjects will remain in the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Any required laboratory sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c  Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes. For visits where a subject is receiving an infusion of any study compounds, vital signs will be collected at the 
following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is 
discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if clinically indicated. 
e  Chemistry panel to include laboratory assessments noted in Table 17. 
f  Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and ctDNA/ctRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit. 
i  Tumor imaging by CT scan or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6. RECIST and irRC documentation to 
be completed at each assessment period. The same mode of imaging is required to be carried through each subject’s respective treatment period. 


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APPENDIX 1. SPONSOR SIGNATURE 
 
Study Title: 
NANT Squamous Cell Carcinoma (SCC) Vacci ne: Molecularly 
informed integrated imm unotherapy com bini ng innate high- 
affinity natural k iller (haNK) cell therapy with adenoviral and 
yeast-based vaccines to induce T-cell responses i n subjects with 
sec who have progressed on or after platinum-based 
chemotherapy and anti-program med cell death protein 1 
(PD-1)/programmed death-ligand I (PD-L I ) therapy. 
Study Num ber: 
QUILT-3.090 
Version Num ber: 
5 
Final Date: 
01 August 2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel  contributed to writing and/or approving this protocol: 
Date 45 !- µ/b 
ee, 
r Vice President Adult Medical Affairs, 
antKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email:  John.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 Amendment 5 
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 TITLE PAGE 
NANT SQUAMOUS CELL CARCINOMA (SCC) 
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 SCC WHO HAVE 
PROGRESSED ON OR AFTER PLATINUM-BASED 
CHEMOTHERAPY AND ANTI-PROGRAMMED CELL 
DEATH PROTEIN 1 (PD-1)/PROGRAMMED DEATH-
LIGAND 1 (PD-L1) THERAPY 
Study Number: 
QUILT-3.090 
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 
20 November 2017 
Version 2 
27 December 2017 
Version 3 
01 March 2018 
Version 4 
06 July 2018 
Version 5 
01 August 2018 
Version 6 
03 October 2018 


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantKwest, Inc. 
Name of Investigational Products: 
1. Aldoxorubicin hydrochloride (HCl) 
2. ETBX-011 (adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine) 
3. ETBX-021 (Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine) 
4. ETBX-051 (Ad5 [E1-, E2b-]-Brachyury vaccine) 
5. ETBX-061 (Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine)  
6. GI-4000 (Ras yeast vaccine) 
7. GI-6207 (CEA yeast vaccine) 
8. GI-6301 (Brachyury yeast vaccine)  
9. haNK™, NK-92 [CD16.158V, ER IL-2], Suspension for Infusion (haNK™ for Infusion) 
10. N-803 (also known as ALT-803; recombinant human superagonist interleukin-15 (IL-15) 
complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]) 
Name of Approved Products: 
11. Avelumab (BAVENCIO® injection, for intravenous [IV] use) 
12. Bevacizumab (AVASTIN® solution for IV infusion) 
13. Capecitabine (XELODA® tablets, for oral use) 
14. Cetuximab (ERBITUX® injection, for IV infusion) 
15. Cisplatin (CISplatin injection) 
16. Cyclophosphamide (Cyclophosphamide Capsules, for oral use; or Cyclophosphamide Tablets, 
USP) 
17. 5-Fluorouracil (5-FU; Fluorouracil Injection, for IV use only) 
18. Leucovorin (LEUCOVORIN Calcium for Injection, for IV or intramuscular [IM] use) 
19. Nab-paclitaxel (ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles for 
injectable suspension] [albumin-bound]) 
20. Necitumumab (Portrazza® injection) 
21. Stereotactic body radiation therapy (SBRT) 


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Name of Active Ingredients: 
Investigational Products 
1. Aldoxorubicin HCl 
2. Ad5 [E1-, E2b-]-CEA 
3. Ad5 [E1-, E2b-]-HER2 
4. Ad5 [E1-, E2b-]-Brachyury 
5. Ad5 [E1-, E2b-]-MUC1  
6. GI-4014 expressing mutations in RAS at codon 12 (G12V), and codon 61 (Q61R and Q61L); 
GI-4015 expressing mutations in RAS at codon 12 (G12C), and codon 61 (Q61R and Q61L); 
GI-4016 expressing mutations in RAS at codon 12 (G12D) and codon 61 (Q61R and Q61L) and 
GI-4020 expressing mutations in RAS at codon 12 (G12R) and codon 61 (Q61L and Q61H) 
7. Recombinant yeast based vaccine expressing the full length human carcinoembryonic antigen 
(CEA), with a modified gene coding sequence to code for a single amino acid substitution 
(asparagine to aspartic acid) at the native protein amino acid position 610 
8. Recombinant yeast based vaccine expressing the human brachyury oncoprotein  
9. NK-92 [CD16.158V, ER IL2] cells 
10. N-803, recombinant human superagonist interleukin-15 (IL-15) complex (also known as 
IL-15N72D:IL-15RαSu/IgG1 Fc complex)  
Approved Products 
11. Avelumab 
12. Bevacizumab 
13. Capecitabine 
14. Cetuximab 
15. Cisplatin  
16. Cyclophosphamide (anhydrous) 
17. Fluorouracil, USP 
18. Leucovorin (calcium salt) 
19. Paclitaxel, USP 
20. Necitumumab 
21. Radiation 


NANT Squamous Cell Carcinoma Vaccine 
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Clinical Trial Protocol: QUILT-3.090 Amendment 5 
 
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Title of Study: 
NANT Squamous Cell Carcinoma (SCC) 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 SCC who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) 
therapy. 
Study Number: 
QUILT-3.090 
Study Phase: 
Phase 1b/2 (Simon’s two-stage optimal design) 
Study Objectives: 
Phase 1b 
• 
The primary objective is to evaluate the overall safety profile of the NANT SCC Vaccine 
regimen in subjects with SCC who have progressed on or after platinum-based chemotherapy 
and anti-PD-1/PD-L1 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 cell-free circulating DNA (cfDNA) and RNA (cfRNA); and their 
correlations with subject outcomes. 
Phase 2  
• 
The primary objective is to determine the efficacy of the NANT SCC Vaccine regimen as 
assessed by ORR using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 
based on Blinded Independent Central Review (BICR). 
• 
Secondary objectives are to determine additional measures of safety and efficacy (ORR by 
immune-related response criteria (irRC), 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 cfDNA and cfRNA; and their 
correlations with subject outcomes. 
Study Design: 
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in 
subjects with SCC who have progressed on or after previous platinum-based chemotherapy and 
anti-PD-1/PD-L1 therapy. Phase 2 will be based on Simon’s two-stage optimal design. 
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 


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the combination therapy is tolerable. 
Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. 
Subjects will continue induction treatment for up to 1 year. 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 and Sponsor’s discretion. Subjects may remain in the maintenance phase of the study for up 
to 1 year.  
Treatment in the study will be discontinued if the subject experiences confirmed progressive disease (PD) 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator 
feels it is no longer in the subject’s best interest to continue treatment. Subjects with an initial assessment 
of PD per RECIST Version 1.1 may, at the discretion of the Investigator, continue to receive study 
treatment until PD is confirmed as detailed in Section 6.1.2. The time on study treatment, including both 
the induction and maintenance phases, is up to 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 cfDNA/cfRNA analyses, as described in Section 6.4.2 and 
Section 6.4.3, respectively. 
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the 
induction phase, and every 12 weeks during the maintenance phase until progression occurs by computed 
tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance 
with RECIST Version 1.1 and irRC. The same mode(s) of assessment used to identify/evaluate lesions at 
screening should be used throughout the course of the study unless subject safety necessitates a change 
(eg, allergic reaction to contrast media). Unscheduled tumor assessments should be carried out if the 
investigator observes any signs or symptoms of PD. When disease progression per RECIST Version 1.1 is 
initially observed, experimental treatment may continue and an imaging assessment should be done 
4-6 weeks after the initial PD assessment to rule out tumor pseudoprogression. If pseudoprogression is 
observed, the subject is allowed to continue experimental treatment and response assessments will 
continue every 8 or 12 weeks and will be evaluated per irRC. For subjects exhibiting a response (PR or 
CR), a confirmatory imaging assessment should be done 4–6 weeks after the initial response.  
Prospective Tumor Molecular Profiling 
Prospective tumor molecular profiling will be performed on FFPE tumor tissue and whole blood (subject-
matched normal comparator against the tumor tissue) collected prior to treatment on this study. 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. 
Prospective tumor molecular profiling will be conducted to inform RAS mutational status and will be used 
to determine whether GI-4000 (RAS) will be administered. Subjects will receive GI-4000 (RAS) if their 
tumor is positive for specific RAS mutations, as determined by whole genome sequencing.  
GI-4000 (RAS) administration will be initiated as soon as results from tumor molecular profiling are 
available. All subjects will receive other agents regardless of their tumor molecular profile. 
Induction Phase: 
Treatment in the induction phase will consist of repeated 3-week cycles for a maximum treatment period 
of 1 year, as follows: 
Day 1, every 3 weeks for 2 cycles: 
• 
Bevacizumab (5 mg/kg IV) 


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Day 1, every 3 weeks:  
• 
Cisplatin (32 mg/m2 IV) 
• 
Leucovorin (20 mg/m2 IV bolus) 
• 
Nab-paclitaxel (125 mg IV) 
Days 1–5, every 3 weeks: 
• 
Cyclophosphamide (25 mg by mouth [PO] twice a day [BID]) 
• 
5-FU (1500 mg/m2 continuous IV infusion over 85–96 hours) 
Day 5 (± 1 day), every 3 weeks for 3 cycles then every 9 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and 
ETBX-061 (MUC1) (1 × 1011 virus particles [VP]/vaccine/dose subcutaneously [SC]) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury)  
(40 yeast units [YU]/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be 
administered, as described above. 
Day 8, every 3 weeks: 
• 
Aldoxorubicin HCl (100 mg/m2 IV)  
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
≤ 4 cycles) 
Days 8–12, every 3 weeks: 
• 
 Cyclophosphamide (25 mg PO daily) 
Day 9, every 3 weeks: 
• 
Avelumab (10 mg/kg IV)  
• 
haNK (2 × 109 cells/dose IV) 
• 
N-803 (15 μg/kg SC) 
Day 11, every 3 weeks:  
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with head and neck squamous cell carcinoma (HNSCC), while necitumumab will be 
administered to subjects with squamous non-small cell lung cancer (NSCLC).  
• 
haNK (2 × 109 cells/dose IV) 
 


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Day 15, every 3 weeks: 
• 
Nab-paclitaxel (100 mg IV) 
• 
SBRT (not to exceed 8 Gy, exact dose to be determined by the radiation oncologist; for 
≤ 4 cycles) 
Day 16, every 3 weeks: 
• 
Cetuximab (250 mg/m2 IV) 
OR 
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with HNSCC, while necitumumab will be administered to subjects with squamous 
NSCLC. 
• 
haNK (2 × 109 cells/dose IV) 
Maintenance Phase: 
The duration of the maintenance phase will be up to 1 year following completion of the last treatment in 
the induction phase. The maintenance phase will consist of repeated 2-week cycles, as follows: 
Day 1, every 2 weeks:  
• 
Aldoxorubicin HCl (60 mg/m2 IV) 
• 
Nab-paclitaxel (100 mg IV) 
Days 1–5, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO BID) 
Days 1, 3, and 5, every 2 weeks: 
• 
Capecitabine (650 mg/m2 PO BID; up to a maximum of 1,000 mg per dose) 
Day 2, every 2 weeks:  
• 
Avelumab (10 mg/kg IV) 
• 
Cetuximab (250 mg/m2 IV) 
OR  
necitumumab (400 mg IV) 
Either cetuximab or necitumumab will be administered. Cetuximab will be administered to 
subjects with HNSCC, while necitumumab will be administered to subjects with squamous 
NSCLC. 
 
• 
haNK (2 × 109 cells/dose IV) 
• 
N-803 (15 µg/kg SC) 


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Day 5 (± 1 day), every 8 weeks thereafter: 
• 
Ad5-based vaccines: ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), and 
ETBX-061 (MUC1) (1 × 1011 VP/vaccine/dose SC) 
• 
Yeast-based vaccines: GI-4000 (RAS), GI-6207 (CEA), and GI-6301 (Brachyury)  
(40 YU/vaccine/dose SC) 
Prospective tumor molecular profiling will determine whether GI-4000 (RAS) will be 
administered, as described above. 
Days 8–12, every 2 weeks: 
• 
Cyclophosphamide (25 mg PO daily) 
Phase 1b 
Primary Endpoint: 
• 
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.03. 
Secondary Endpoints: 
• 
ORR by RECIST Version 1.1. 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 
• 
PFS by irRC. 
• 
OS. 
• 
DOR by RECIST Version 1.1 and irRC. 
• 
DCR (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST 
Version 1.1 and irRC. 
• 
QoL by PROs. 
Exploratory Endpoints: 
• 
Tumor molecular profiles and correlations with subject outcomes. 
• 
Therapy-induced changes in immune responses and correlations with subject outcomes. 
• 
Molecular changes in cfDNA and cfRNA and correlations with subject outcomes. 
Phase 2 
Primary Endpoint: 
• 
ORR by RECIST Version 1.1. 
Secondary Endpoints: 
• 
ORR by irRC. 
• 
PFS by RECIST Version 1.1. 


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• 
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 and 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 cfDNA and cfRNA and correlations with subject outcomes. 
In the phase 1b portion of the study, response will be assessed by a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. A charter for the 
conduct of BICR will be prepared by the vendor selected to perform the independent review. 
Enrollment (planned): 
In the phase 1b portion of the study, 6 to 24 subjects will be enrolled. 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, 21 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 20 subjects will be 
enrolled in the second stage, for a total of 41 subjects in the phase 2 portion of the study. The maximum 
total enrollment in the study is 65 subjects. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or 
Independent Ethics Committee (IEC) guidelines. 
3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after platinum-
based chemotherapy and anti-PD-1/PD-L1 therapy. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 
5. Have at least 1 measurable lesion of ≥ 1.0 cm. 
6. Must have a recent 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. 


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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, 
or 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. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL). 
c. Platelet count < 75,000 cells/mm3. 
d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has 
documented Gilbert’s syndrome). 
e. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) 
> 2.5 × ULN (> 5 × ULN in subjects with liver metastases). 
f. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or 
>10 × ULN in subjects with bone metastases). 
g. Serum creatinine > 2.0 mg/dL or 177 μmol/L. 
h. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3. 
 
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically 
significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial 
infarction within 6 months prior to first study medication; unstable angina; congestive heart 
failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring 
medication. Subjects with uncontrolled hypertension should be medically managed on a stable 
regimen to control hypertension prior to study entry. 
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction 
(LVEF) 10% below the institution’s lower limit of predicted normal. 


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8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring 
continuous oxygen therapy. 
9. Positive results of screening test for human immunodeficiency virus (HIV). 
10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose 
equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. 
Short term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have 
known contrast allergies is allowed. 
11. Known hypersensitivity to any component of the study medication(s). 
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction 
with any of the study medications. 
13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including 
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, 
ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 
inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and 
St John's Wort) within 14 days before study day 1. 
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer 
(rifampin) within 14 days before study day 1. 
15. Participation in an investigational drug study or history of receiving any investigational treatment 
within 30 days prior to screening for this study, except for testosterone-lowering therapy in men 
with prostate cancer. 
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the 
protocol. 
17. Concurrent participation in any interventional clinical trial. 
18. Pregnant and nursing women. 
Products, Dosage, and Mode of Administration: 
Investigational Products 
Dosage 
Mode of Administration 
Aldoxorubicin HCl 
100 mg/m2 (induction);  
60 mg/m2 (maintenance) 
IV 
ETBX-011 (CEA) 
1 × 1011 VP/dose  
SC 
ETBX-021 (HER2) 
1 × 1011 VP/dose  
SC 
ETBX-051 (Brachyury) 
1 × 1011 VP/dose  
SC 
ETBX-061 (MUC1) 
1 × 1011 VP/dose  
SC 
GI-4000 (RAS) 
40 YU/dose 
SC 
GI-6207 (CEA) 
40 YU/dose 
SC 
GI-6301 (Brachyury) 
40 YU/dose 
SC 
haNK  
2 × 109 cells/dose  
IV 


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N-803 
15 µg/kg  
SC 
Approved Products 
Dosage 
Mode of Administration 
Avelumab 
10 mg/kg 
IV 
Bevacizumab 
5 mg/kg 
IV 
Capecitabine 
650 mg/m2 BID up to a maximum of  
1,000 mg per dose 
PO 
Cetuximab 
250 mg/m2 
IV 
Cisplatin 
32 mg/m2 
IV 
Cyclophosphamide  
25 mg BID (days 1-5);  
25 mg once daily (days 8-12) 
PO  
5-FU 
1500 mg/m2  
85- to 96-hour continuous 
IV infusion 
Leucovorin  
20 mg/m2  
IV bolus 
Nab-paclitaxel  
125 mg (day 1 of induction); 100 mg (day 15 
of induction and day 1 of maintenance) 
IV 
Necitumumab 
400 mg 
IV 
SBRT 
8 Gy maximum (exact dose to be determined 
by the radiation oncologist) 
External beam radiation 
Duration of Treatment:  
• 
Induction phase: 8 weeks (minimum) to 1 year (maximum) 
• 
Maintenance phase: Up to 1 year. 
Subjects will be treated for up to 2 years (up to 1 year in each treatment phase), or until they experience 
confirmed PD, unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the 
Investigator feels it is no longer in their best interest to continue treatment. 
Duration of Follow-up:  
Subjects who discontinue study treatment should remain in the study and continue to be followed for: 
• 
CT or MRI imaging and response assessments (see Section 6.1.2) 
• 
Collection of vital status every 90 days (± 14 days). 
Subjects should be followed until either death (any cause) or for a minimum of 24 months past 
administration of the first dose of study drug. 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable. 


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Evaluation of Endpoints: 
Safety: 
Safety endpoints include assessments of treatment-emergent AEs, SAEs, and clinically significant 
changes in safety laboratory tests, physical examinations, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and vital signs. All subjects will be evaluable for toxicity from the time of their first study 
treatment. Toxicities will be graded using the NCI CTCAE Version 4.03. 
Efficacy: 
ORR and PFS will be assessed by CT or MRI of target and non-target lesions every 8 weeks during the 
induction phase and every 12 weeks during the maintenance phase and will be evaluated in accordance 
with RECIST Version 1.1 and irRC. 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 4–6 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 a local independent radiologist; in the 
phase 2 portion of the study, the primary assessment of response will be based on BICR. 
An assessment of QoL will be conducted via PROs using the Functional Assessment of Cancer Therapy-
Head and Neck (FACT-H&N) or Functional Assessment of Cancer Therapy-Lung (FACT-L) instruments 
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 Analyses: 
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 SCC Vaccine regimen will be evaluated by 
standard immune assays. Correlations between therapy-induced immune changes and subject outcomes 
will be assessed. 
cfDNA/cfRNA Analysis: cfDNA and cfRNA will be extracted from plasma obtained from whole blood. 
Expression levels of specific tumor- and immune-related analytes will be assessed by quantitative 
real-time polymerase chain reaction (qPCR) and possibly other methods (eg, DNA/RNA sequencing) and 
analyzed for correlations with subject outcomes. 


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Statistical Methods: 
This phase 1b/2 study will examine the overall safety profile and preliminary efficacy of metronomic 
combination therapy in subjects with SCC who have progressed on or after platinum-based chemotherapy 
and anti-PD-1/PD-L1 therapy.  
Safety results will be presented separately for the induction and maintenance phases of treatment as well 
as overall for the entire treatment regimen. Efficacy results will be summarized for the overall treatment 
regimen. 
Overall safety will be assessed by descriptive analyses using tabulated frequencies of AEs by grade using 
CTCAE version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically significant changes in 
safety laboratory tests, physical examinations, ECGs, ECHOs, and vital signs. 
ORR will be evaluated in accordance with RECIST Version 1.1 and irRC. The percentage of subjects 
(and 95% confidence interval [CI]) who achieve a confirmed response will be summarized. DCR will be 
evaluated similar to ORR. PFS, OS, and DOR will be analyzed using Kaplan-Meier methods.  
Descriptive statistics of PROs will be presented. 
Correlations of tumor molecular profiles, therapy-induced changes in immune responses, and molecular 
changes in cfDNA and cfRNA with subject outcomes will be explored. 


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Figure 1: 
Study Treatment Schema 
 


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Figure 2: 
Induction Phase Treatment Schema 
 


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Figure 3: 
Maintenance Phase Treatment Schema 
 


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


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Screening 
Induction Phase Treatment (repeats every 3 weeks, except where noted)
a 
 
 
Study Week 
 
1 
2 
3 
EOT 
Visit
b 
Unscheduled 
Visit
c 
Study Day 
-28 to -1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
 
 
Laboratory Assessments 
Chemistry panelk 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Hematologyl 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Urinalysis 
X 
Xj 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Pregnancy testm 
X 
Xj 
Every 6 weeks 
X 
 
Serum virology (HIV)n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine HER2 expression 
and RAS mutational statuso 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for tumor 
molecular profilingp 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect whole blood for 
immunology analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect whole blood for 
cfDNA/cfRNA analysisq 
X 
Every 6 weeks during routine blood draws 
X 
 
Collect historic tumor biopsy 
specimen for tumor molecular 
profilingr 
X 
 
 
 
Tumor biopsyr 
X 
8 weeks after the start of treatment 
 
 
Additional tumor biopsy 
 
May be collected at any time point, as clinically indicated at the Investigator’s discretion. 
 
 
Tumor Imaging and Assessments 
CT or MRIs 
X 
Every 8 weeks 
X 
 
a Subjects will remain in the induction phase of the study for up to 1 year. Treatment will continue in the induction phase until the subject experiences confirmed 
PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Those who have a CR in the induction phase will enter the maintenance phase of the study. 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 and Sponsor’s discretion. Any required laboratory 
sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 
b End-of-treatment visit must be performed 30 (±5 days) after the last study treatment. 


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


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s Tumor imaging by CT scan or MRI will be performed at screening and every 8 weeks during the induction phase, as described in Section 6. All screening tumor 
imaging assessments should be performed based on the subject's qualifying scan obtained within 28 days prior to the start of treatment. RECIST and irRC 
documentation are to be completed at each assessment period.  


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


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Maintenance Phase Treatment (repeats every 2 weeks, except where noted)
a 
 
 
Study Week 
1 
2 
EOT Visit
b 
Unscheduled 
Visit
c 
Study Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
 
 CT or MRI
i 
X 
Every 12 weeks 
X 
 
a Subjects will remain in the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD 
or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject’s best interest to 
continue treatment. Any required laboratory sample collection (eg, blood draws, urinalysis) may be performed within a 3-day window of the time indicated. 
b EOT visit must be performed 30 (±5 days) after the last study treatment. 
c Additional assessments performed during an unscheduled visit are at the discretion of the PI or treating physician and must be recorded in the subject’s source 
documents and on the Unscheduled Visit eCRF. 
d Vital signs of temperature, heart rate, blood pressure, and respiratory rate will be assessed at every visit. Vital signs are to be obtained after the subject has been 
in a seated resting position for at least 5 minutes. For visits where a subject is receiving an infusion of any study compounds, vital signs will be collected at the 
following time points in relation to the start of first infusion of the day: prior to infusion, 15 minutes post, 30 minutes post, and hourly until the subject is 
discharged. Temperature will be documented each visit at the first pre-infusion assessment of vital signs and subsequently if clinically indicated. 
e Chemistry panel to include laboratory assessments noted in Table 17. 
f Hematology to include CBC with differential (5 part) and platelets with hemoglobin and hematocrit. 
g Serum pregnancy test for females of child-bearing potential. 
h Blood collection for exploratory immunology and cfDNA/cfRNA analyses will be performed every 8 weeks in the maintenance phase during routine blood 
draws, and at the end-of-treatment visit.  
i Tumor imaging by CT scan or MRI will be performed every 12 weeks in the maintenance phase, as described in Section 6. RECIST and irRC documentation to 
be completed at each assessment period. The same mode of imaging is required to be carried through each subject’s respective treatment period. 


NANT Squamous Cell Carcinoma Vaccine 
NantK west, Inc. 
Clinical Trial Protocol: QU ILT-3.090 Amendment 5 
APPENDIX 1. SPONSOR SIGNATURE 
Study Title: 
NANT Squamous Cell Carcinoma (SCC) 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 
sec who have progressed on or after platinum-based 
chemotherapy and anti-programmed cell death protein 1 
(PD-1 )/programmed death-ligand I (PD-LI) therapy. 
Study Number: 
QUILT-3.090 
Version Numoer: 
.6 
Final Date: 
03 October 2018 
This clinical trial protocol was subject to critical review and has been approved by NantKwest. 
The following personnel contributed to writing and/or approving this protocol: 
Sig 
Se ior 
ice President Adult Medical Affairs, 
N 
t1'.\\e::.I Inc. 
9920 .Jefferson Blvd 
Culver CiLy, CA 90232 
Enai : Jol.n.Lee@Nantkwest.com 
Cd. !·hon.:: + 1-605-610-639 l 
Confidential and Proprietary 
17 l 
Date: /[) """ 5--/g