Phase I Study of Ad5 [E1-, E2b-]-HER2/Neu Vaccine (ETBX-021) in Subjects With Unresectable Locally Advanced or Metastatic HER2-Low-Expressing (IHC 1+/2+) Breast Cancer
Phase: PHASE1
Conditions: Cancer
Sponsor: NantBioScience, Inc.

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 1 
 
PROTOCOL NUMBER CMS-005 
PHASE I STUDY OF AD5 [E1-, E2B-]-HER2/NEU 
VACCINE (ETBX-021) IN SUBJECTS WITH 
UNRESECTABLE LOCALLY ADVANCED OR 
METASTATIC HER2-EXPRESSING BREAST CANCER 
 
IND Number: 
016,871 
Principal Investigator: 
Hatem Soliman, MD 
Moffitt Cancer Center 
12902 Magnolia Drive 
Tampa, Florida 33612 
Email: hatem.soliman@moffitt.org 
Office Phone: 813-745-4933  
Clinical Study Sponsor: 
NantBioScience, Inc. 
Sponsor Contact:  
(For medical questions/emergencies) 
Wayne R. Godfrey, MD 
Chief Medical Officer 
Medical and Safety Monitor 
Email: wayne@etubics.com 
Office Phone: 206-838-5110, Ext 9 
Mobile Phone: 650-521-2770 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Jackie Imm, BA 
Clinical Trial Manager 
Email: Jackie.Imm@NantBio.com 
Office Phone: 919-694-6315 
SAE Reporting: 
Submit SAE Reports to one (1) of the 
following: 
SAE Email: SAE.Reporting@NantBio.com 
Fax: 800-853-3497 
 
Protocol Version 
Date 
Original Protocol CMS-005 
26 February 2016 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 2 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantBioScience, Inc. 
Name of Investigational Product: 
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection (ETBX-021) 
Name of Active Ingredient: 
Ad5 [E1-, E2b-]-HER2/neu 
Title of Study:  
Phase I Study of Ad5 [E1-, E2b-]-HER2/neu Vaccine (ETBX-021) in Subjects with Unresectable 
Locally Advanced or Metastatic HER2-Expressing Breast Cancer 
Study Number: 
CMS-005 
Study Phase: 
Phase I 
Primary Objectives: 
• 
Determine the overall safety and recommended phase 2 dose of ETBX-021 when administered 
subcutaneously (SC) every 3 weeks for three injections followed by three booster injections at 
3-month intervals to subjects with HER2-expressing breast cancer. 
Secondary Objectives: 
• 
Make preliminary assessments of objective response rate (ORR), disease control rate (DCR), 
duration of response, progression-free survival (PFS), and overall survival (OS) in subjects 
with HER2-expressing breast cancer treated with ETBX-021. 
Exploratory Objectives: 
• 
Evaluate the immunogenicity of ETBX-021 and determine the genomic and proteomic profile 
of subjects’ tumors to identify gene mutations, gene amplifications, RNA-expression levels, 
and protein-expression levels. Correlations between genomic/proteomic profiles and efficacy 
outcomes will be assessed. 
Primary Endpoints: 
• 
Dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or highest tested dose 
(HTD). 
• 
Treatment-emergent adverse event (AEs) and serious adverse events (SAEs). 
• 
Clinically significant changes in safety laboratory tests, physical examinations, 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF), and vital signs. 
Secondary Endpoints: 
• 
ORR (confirmed complete or partial response) according to the Response Evaluation Criteria 
in Solid Tumors (RECIST) Version 1.1. 
• 
DCR (confirmed response or stable disease lasting for at least 6 months). 
• 
Duration of response. 
• 
PFS. 
• 
OS. 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 3 
 
Exploratory Endpoints: 
• 
Immunogenicity of ETBX-021 by flow cytometric analysis of T-cell frequency, activation 
status, cytokine profiles, and antibody levels. 
• 
Genetic and proteomic profiling and correlates with efficacy. 
Study Design: 
This is a Phase I trial in subjects with unresectable locally advanced or metastatic HER2-low 
expressing (IHC 1+ or 2+) breast cancer. The study will be conducted in two parts: the first part will 
involve dose escalation using a 3 + 3 design, and the second part will involve the expansion of the 
MTD or HTD to further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 
3 to 6 subjects will be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for 
dose-limiting toxicities (DLTs). 
• 
Cohort 1: 5 x 1010 virus particles (VP). 
• 
Cohort 2: 5 x 1011 VP. 
• 
If needed, dose de-escalation cohort (cohort -1): 5 x 109 VP. 
Dose expansion will occur when the MTD or HTD has been determined. An additional 12 subjects will 
be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD or HTD. 
Enrollment (planned): 
Up to 30 subjects will be enrolled in the study. In the dose escalation component, 3 to 6 subjects will be 
sequentially enrolled starting at Cohort 1. In the dose expansion component (i.e., once the MTD or 
HTD has been identified), an additional 12 subjects will be enrolled for a total of 18 subjects in the 
MTD/HTD cohort to obtain further safety, preliminary efficacy, and immunogenicity data.  
Diagnosis and Main Criteria for Inclusion: 
Subjects must have histologically confirmed unresectable locally advanced or metastatic breast cancer 
that expresses HER2 (IHC 1+ or 2+). Subjects with HER2 IHC 3+ tumors are excluded. 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-021 (5 x 109, 5 x 1010, or 5 x 1011 VP in 1.0 mL) will be administered by SC injection every 
3 weeks for 3 injections, followed by 3 booster injections at 3-month intervals. 
Duration of Treatment:  
Subjects will receive treatment for up to 42 weeks (injections at 0, 3, and 6 weeks with booster 
injections at 18, 30, and 42 weeks) or until they experience progressive disease or unacceptable 
toxicity, withdraw consent, or if the Investigator feels it is no longer in their best interest to continue 
treatment. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Criteria for Evaluation: 
Safety: Safety endpoints include assessments of DLT, MTD or HTD, treatment-emergent AEs, SAEs, 
and clinically significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and 
vital signs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response (ORR and DCR) will be evaluated according to RECIST Version 1.1; 
duration of response, PFS, and OS will also be evaluated. 
Exploratory Immune Analysis: Immune responses will be detected and quantified in flow cytometry-
based and serum assays. 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 4 
 
Exploratory Molecular Profiling and Analysis: Genomic sequencing of tumor cells relative to non-
tumor cells to identify the genomic variances that may contribute to response or disease progression 
and provide an understanding of molecular abnormalities; RNA sequencing to provide expression data 
and give relevance to DNA mutations; and quantitative proteomics to determine the exact amounts of 
specific proteins and to confirm expression of genes predictive of response and disease progression. 
Statistical Methods: 
The rate of DLTs and the MTD or HTD will be assessed. Overall safety will be assessed by descriptive 
analyses using tabulated frequencies of AEs by grade using CTCAE Version 4.03 within dose cohorts 
and for the overall study population in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and vital signs. 
ORR and DCR will be evaluated according to RECIST Version 1.1 by dose cohort and overall; 
duration of response will also be evaluated. PFS and OS will be analyzed using Kaplan-Meier methods 
by dose cohort and overall. 

 
ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 23 
 
Figure 1: 
Study Design and Treatment Schema 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
 
Confidential and Proprietary 
Page 34 
Table 3: 
Time and Events Schedule 
Assessment 
Screening 
Baseline 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -7 
Day 
-7 to 1 
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
 
 
Clinic Visit 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Heighta, 
Weight, ECOG 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Medical Historyb 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm HER2 Expression 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
12-Lead ECG 
X 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Echocardiogram/MUGAd 
X 
 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Confirm Contraceptive Measurese 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Injection/ Injection 
Site Reaction Monitoringf 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Dispensation of Subject Diary 
Cardg 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Review of Subject Diary Cardg 
 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 
Confidential and Proprietary 
Page 35 
Assessment 
Screening 
Baseline 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -7
Day 
-7 to 1
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
Telephone Contact 72 Hours Post 
Injection 
X 
X 
X 
X 
X 
X 
Tumor Imagingh 
X 
X 
X 
X 
X 
X 
Pregnancy Testi 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Chemistry Panel 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC, Differential, Platelets 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
Serum Virology (HIV, HBV, 
HCV) 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Immune Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Genomics and 
Proteomics Molecular Analysis 
X 
Telephone Follow Upj 
X 

ETBX-021
NantBioScience, Inc.
Clinical Trial Protocol:  CMS-005 Amendment 1 
Confidential and Proprietary 
Page 1 
PROTOCOL NUMBER CMS-005 
PHASE I STUDY OF AD5 [E1-, E2B-]-HER2/NEU 
VACCINE (ETBX-021) IN SUBJECTS WITH 
UNRESECTABLE LOCALLY ADVANCED OR 
METASTATIC HER2-EXPRESSING BREAST CANCER
IND Number: 
016,871 
Principal Investigator: 
Hatem Soliman, MD 
Moffitt Cancer Center 
12902 Magnolia Drive 
Tampa, Florida 33612 
Email: hatem.soliman@moffitt.org 
Office Phone: 813-745-4933  
Clinical Study Sponsor: 
NantBioScience, Inc. 
Sponsor Contact:  
(For medical questions/emergencies) 
Wayne R. Godfrey, MD 
Chief Medical Officer 
Medical and Safety Monitor 
Email: wayne@etubics.com 
Office Phone: 206-838-5110, Ext 9 
Mobile Phone: 650-521-2770 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Jackie Imm, BA 
Clinical Trial Manager 
Email: Jackie.Imm@NantBio.com 
Office Phone: 919-694-6315 
SAE Reporting: 
Submit SAE Reports to one (1) of the 
following: 
SAE Email: SAE.Reporting@NantBio.com 
Fax: 800-853-3497 
Protocol Version 
Date 
Original Protocol CMS-005 
26 February 2016 
Protocol CMS-005 Amendment 1 
21 April 2016 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
 
Confidential and Proprietary 
Page 2 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantBioScience, Inc. 
Name of Investigational Product: 
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection (ETBX-021) 
Name of Active Ingredient: 
Ad5 [E1-, E2b-]-HER2/neu 
Title of Study:  
Phase I Study of Ad5 [E1-, E2b-]-HER2/neu Vaccine (ETBX-021) in Subjects with Unresectable 
Locally Advanced or Metastatic HER2-Expressing Breast Cancer 
Study Number: 
CMS-005 
Study Phase: 
Phase I 
Primary Objectives: 
• 
Determine the overall safety and recommended phase 2 dose of ETBX-021 when administered 
subcutaneously (SC) every 3 weeks for three injections followed by three booster injections at 
3-month intervals to subjects with HER2-expressing breast cancer. 
Secondary Objectives: 
• 
Make preliminary assessments of objective response rate (ORR), disease control rate (DCR), 
duration of response, progression-free survival (PFS), and overall survival (OS) in subjects 
with HER2-expressing breast cancer treated with ETBX-021. 
Exploratory Objectives: 
• 
Evaluate the immunogenicity of ETBX-021 and determine the genomic and proteomic profile 
of subjects’ tumors to identify gene mutations, gene amplifications, RNA-expression levels, 
and protein-expression levels. Correlations between genomic/proteomic profiles and efficacy 
outcomes will be assessed. 
Primary Endpoints: 
• 
Dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or highest tested dose 
(HTD). 
• 
Treatment-emergent adverse event (AEs) and serious adverse events (SAEs). 
• 
Clinically significant changes in safety laboratory tests, physical examinations, 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF), and vital signs. 
Secondary Endpoints: 
• 
ORR (confirmed complete or partial response) according to the Response Evaluation Criteria 
in Solid Tumors (RECIST) Version 1.1. 
• 
DCR (confirmed response or stable disease lasting for at least 6 months). 
• 
Duration of response. 
• 
PFS. 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
 
Confidential and Proprietary 
Page 3 
 
• 
OS. 
Exploratory Endpoints: 
• 
Immunogenicity of ETBX-021 by flow cytometric analysis of T-cell frequency, activation 
status, cytokine profiles, and antibody levels. 
• 
Genetic and proteomic profiling and correlations with efficacy. 
Study Design: 
This is a Phase I trial in subjects with unresectable locally advanced or metastatic HER2-low 
expressing (IHC 1+ or 2+) breast cancer. The study will be conducted in two parts: the first part will 
involve dose escalation using a 3 + 3 design, and the second part will involve the expansion of the 
MTD or HTD to further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 
3 to 6 subjects will be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for 
dose-limiting toxicities (DLTs). 
• 
Cohort 1: 5 x 1010 virus particles (VP). 
• 
Cohort 2: 5 x 1011 VP. 
• 
If needed, dose de-escalation cohort (cohort -1): 5 x 109 VP. 
Dose expansion will occur when the MTD or HTD has been determined. An additional 12 subjects will 
be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD or HTD. 
Enrollment (planned): 
Up to 30 subjects will be enrolled in the study. In the dose escalation component, 3 to 6 subjects will be 
sequentially enrolled starting at Cohort 1. In the dose expansion component (i.e., once the MTD or 
HTD has been identified), an additional 12 subjects will be enrolled for a total of 18 subjects in the 
MTD/HTD cohort to obtain further safety, preliminary efficacy, and immunogenicity data.  
Diagnosis and Main Criteria for Inclusion: 
Subjects must have histologically confirmed unresectable locally advanced or metastatic breast cancer 
that expresses HER2 (IHC 1+ or 2+). Subjects with HER2 IHC 3+ tumors are excluded. 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-021 (5 x 109, 5 x 1010, or 5 x 1011 VP in 1.0 mL) will be administered by SC injection every 
3 weeks for 3 injections, followed by 3 booster injections at 3-month intervals. 
Duration of Treatment:  
Subjects will receive treatment for up to 42 weeks (injections at 0, 3, and 6 weeks with booster 
injections at 18, 30, and 42 weeks) or until they experience progressive disease or unacceptable 
toxicity, withdraw consent, or if the Investigator feels it is no longer in their best interest to continue 
treatment. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Criteria for Evaluation: 
Safety: Safety endpoints include assessments of DLT, MTD or HTD, treatment-emergent AEs, SAEs, 
and clinically significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and 
vital signs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response (ORR and DCR) will be evaluated according to RECIST Version 1.1; 
duration of response, PFS, and OS will also be evaluated. 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
 
Confidential and Proprietary 
Page 4 
 
Exploratory Immune Analysis: Immune responses will be detected and quantified in flow cytometry-
based and serum assays. 
 
Exploratory Molecular Profiling and Analysis and its Rationale: Genomic sequencing of tumor 
cells from tissue relative to non-tumor cells from whole blood will be profiled to identify the genomic 
variances that may contribute to response or disease progression and provide an understanding of 
molecular abnormalities. RNA sequencing will be conducted to provide expression data and give 
relevance to DNA mutations. Quantitative proteomics analysis will be conducted to determine the 
exact amounts of specific proteins and to confirm expression of genes that are correlative of response 
to vaccine immunotherapy and disease progression. All genomic, transcriptomic, and proteomic 
molecular analyses will be retrospective and exploratory. 
Statistical Methods: 
The rate of DLTs and the MTD or HTD will be assessed. Overall safety will be assessed by descriptive 
analyses using tabulated frequencies of AEs by grade using CTCAE Version 4.03 within dose cohorts 
and for the overall study population in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and vital signs. 
ORR and DCR will be evaluated according to RECIST Version 1.1 by dose cohort and overall; 
duration of response will also be evaluated. PFS and OS will be analyzed using Kaplan-Meier methods 
by dose cohort and overall. 

 
ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
 
Confidential and Proprietary 
Page 24 
 
Figure 1: 
Study Design and Treatment Schema 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
 
Confidential and Proprietary 
Page 35 
Table 3: 
Time and Events Schedule 
Assessment 
Screening
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1 
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
 
 
Clinic Visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Heighta, 
Weight, ECOG 
Xb 
Xb 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Medical Historyc 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm HER2 Expressiond 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signse 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
12-Lead ECG 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Echocardiogram/MUGAf 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Confirm Contraceptive Measuresg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Injection/ Injection 
Site Reaction Monitoringh 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Dispensation of Subject Diary 
Cardi 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 1 
Confidential and Proprietary 
Page 36 
Assessment
Screening
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
Review of Subject Diary Cardi 
X 
X 
X 
X
X
X 
X 
Telephone Contact 72 Hours Post 
Injection 
X 
X 
X
X 
 
X
X 
Tumor Imagingj 
X 
 
X 
X 
 
X
X 
X 
Pregnancy Testk
Xb
Xb 
X 
X
X 
 
X
X 
X 
Urinalysis 
X 
 
X 
 
X
X 
Chemistry Panel 
Xb
Xb 
X 
X 
X 
X 
 
X
X 
X 
CBC, Differential, Platelets 
Xb
Xb 
X 
X 
X 
X 
 
X
X 
X 
Coagulation 
X 
X 
X 
X 
Serum Virology (HIV, HBV, 
HCV)l 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Immune Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Genomics and 
Proteomics Molecular Analysis 
X 
Telephone Follow Upm 
X 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 1 
 
PROTOCOL NUMBER CMS-005 
PHASE I STUDY OF AD5 [E1-, E2B-]-HER2/NEU 
VACCINE (ETBX-021) IN SUBJECTS WITH 
UNRESECTABLE LOCALLY ADVANCED OR 
METASTATIC HER2-LOW-EXPRESSING (IHC 1+/2+) 
BREAST CANCER 
 
IND Number: 
016,871 
Principal Investigator: 
Hatem Soliman, MD 
Moffitt Cancer Center 
12902 Magnolia Drive 
Tampa, Florida 33612 
Email: hatem.soliman@moffitt.org 
Office Phone: 813-745-4933  
Clinical Study Sponsor: 
NantBioScience, Inc. 
Sponsor Contact:  
(For medical questions/emergencies) 
Wayne R. Godfrey, MD 
Chief Medical Officer 
Medical and Safety Monitor 
Email: wayne@etubics.com 
Office Phone: 206-838-5110, Ext 9 
Mobile Phone: 650-521-2770 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Jackie Imm, BA 
Clinical Trial Manager 
Email: Jackie.Imm@NantBio.com 
Office Phone: 919-694-6315 
SAE Reporting: 
Submit SAE Reports to one (1) of the 
following: 
SAE Email: SAE.Reporting@NantBio.com 
Fax: 800-853-3497 
 
Protocol Version 
Date 
Original Protocol CMS-005 
26 February 2016 
Protocol CMS-005 Amendment 1 
20 April 2016 
Protocol CMS-005 Amendment 2 
25 May 2016 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 2 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantBioScience, Inc. 
Name of Investigational Product: 
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection (ETBX-021) 
Name of Active Ingredient: 
Ad5 [E1-, E2b-]-HER2/neu 
Title of Study:  
Phase I Study of Ad5 [E1-, E2b-]-HER2/neu Vaccine (ETBX-021) in Subjects with Unresectable 
Locally Advanced or Metastatic HER2-Low-Expressing (IHC 1+/2+) Breast Cancer 
Study Number: 
CMS-005 
Study Phase: 
Phase I 
Primary Objectives: 
• 
Determine the overall safety and recommended phase 2 dose of ETBX-021 when administered 
subcutaneously (SC) every 3 weeks for three injections followed by three booster injections at 
3-month intervals to subjects with HER2-low-expressing breast cancer. 
Secondary Objectives: 
• 
Make preliminary assessments of objective response rate (ORR), disease control rate (DCR), 
duration of response, progression-free survival (PFS), and overall survival (OS) in subjects 
with HER2-low-expressing breast cancer treated with ETBX-021. 
Exploratory Objectives: 
• 
Evaluate the immunogenicity of ETBX-021 and determine the genomic and proteomic profile 
of subjects’ tumors to identify gene mutations, gene amplifications, RNA-expression levels, 
and protein-expression levels. Correlations between genomic/proteomic profiles and efficacy 
outcomes will be assessed. 
Primary Endpoints: 
• 
Dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or highest tested dose 
(HTD). 
• 
Treatment-emergent adverse event (AEs) and serious adverse events (SAEs). 
• 
Clinically significant changes in safety laboratory tests, physical examinations, 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF), and vital signs. 
Secondary Endpoints: 
• 
ORR (confirmed complete or partial response) according to the Response Evaluation Criteria 
in Solid Tumors (RECIST) Version 1.1. 
• 
DCR (confirmed response or stable disease lasting for at least 6 months). 
• 
Duration of response. 
• 
PFS. 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 3 
 
• 
OS. 
Exploratory Endpoints: 
• 
Immunogenicity of ETBX-021 by flow cytometric analysis of T-cell frequency, activation 
status, cytokine profiles, and antibody levels. 
• 
Genetic and proteomic profiling and correlations with efficacy. 
Study Design: 
This is a Phase I trial in subjects with unresectable locally advanced or metastatic HER2-low-
expressing (IHC 1+ or 2+) breast cancer. The study will be conducted in two parts: the first part will 
involve dose escalation using a 3 + 3 design, and the second part will involve the expansion of the 
MTD or HTD to further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 
3 to 6 subjects will be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for 
dose-limiting toxicities (DLTs). 
• 
Cohort 1: 5 x 1010 virus particles (VP). 
• 
Cohort 2: 5 x 1011 VP. 
• 
If needed, dose de-escalation cohort (cohort -1): 5 x 109 VP. 
Dose expansion will occur when the MTD or HTD has been determined. An additional 12 subjects will 
be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD or HTD. 
Enrollment (planned): 
Up to 30 subjects will be enrolled in the study. In the dose escalation component, 3 to 6 subjects will be 
sequentially enrolled starting at Cohort 1. In the dose expansion component (i.e., once the MTD or 
HTD has been identified), an additional 12 subjects will be enrolled for a total of 18 subjects in the 
MTD/HTD cohort to obtain further safety, preliminary efficacy, and immunogenicity data.  
Diagnosis and Main Criteria for Inclusion: 
Subjects must have histologically confirmed unresectable locally advanced or metastatic breast cancer 
that expresses HER2 (IHC 1+ or 2+). Subjects with HER2 IHC 3+ tumors are excluded. 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-021 (5 x 109, 5 x 1010, or 5 x 1011 VP in 1.0 mL) will be administered by SC injection every 
3 weeks for 3 injections, followed by 3 booster injections at 3-month intervals. 
Duration of Treatment:  
Subjects will receive treatment for up to 42 weeks (injections at 0, 3, and 6 weeks with booster 
injections at 18, 30, and 42 weeks) or until they experience progressive disease or unacceptable 
toxicity, withdraw consent, or if the Investigator feels it is no longer in their best interest to continue 
treatment. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Criteria for Evaluation: 
Safety: Safety endpoints include assessments of DLT, MTD or HTD, treatment-emergent AEs, SAEs, 
and clinically significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and 
vital signs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response (ORR and DCR) will be evaluated according to RECIST Version 1.1; 
duration of response, PFS, and OS will also be evaluated. 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 4 
 
Exploratory Immune Analysis: Immune responses will be detected and quantified in flow cytometry-
based and serum assays. 
 
Exploratory Molecular Profiling and Analysis and its Rationale: Genomic sequencing of tumor 
cells from tissue relative to non-tumor cells from whole blood will be profiled to identify the genomic 
variances that may contribute to response or disease progression and provide an understanding of 
molecular abnormalities. RNA sequencing will be conducted to provide expression data and give 
relevance to DNA mutations. Quantitative proteomics analysis will be conducted to determine the 
exact amounts of specific proteins and to confirm expression of genes that are correlative of response 
to vaccine immunotherapy and disease progression. All genomic, transcriptomic, and proteomic 
molecular analyses will be retrospective and exploratory. 
Statistical Methods: 
The rate of DLTs and the MTD or HTD will be assessed. Overall safety will be assessed by descriptive 
analyses using tabulated frequencies of AEs by grade using CTCAE Version 4.03 within dose cohorts 
and for the overall study population in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and vital signs. 
ORR and DCR will be evaluated according to RECIST Version 1.1 by dose cohort and overall; 
duration of response will also be evaluated. PFS and OS will be analyzed using Kaplan-Meier methods 
by dose cohort and overall. 

 
ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 24 
 
Figure 1: 
Study Design and Treatment Schema 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
 
Confidential and Proprietary 
Page 35 
Table 3: 
Time and Events Schedule 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1 
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
 
 
Clinic Visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Heighta, 
Weight, ECOG 
Xb 
Xb 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Medical Historyc 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm HER2 Expressiond 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signse 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
12-Lead ECG 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Echocardiogram/MUGAf 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Confirm Contraceptive Measuresg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Injection/ Injection 
Site Reaction Monitoringh 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Dispensation of Subject Diary 
Cardi 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol:  CMS-005 Amendment 2 
Confidential and Proprietary 
Page 36 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
Review of Subject Diary Cardi 
X 
X 
X 
X 
X 
X 
X 
Telephone Contact 72 Hours Post 
Injection 
X 
X 
X 
X 
X 
X 
Tumor Imagingj 
X 
X 
X 
X 
X 
X 
Pregnancy Testk 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Chemistry Panel 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
CBC, Differential, Platelets 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
Serum Virology (HIV, HBV, 
HCV)l 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Immune Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Genomics, 
Transcriptomics, and Proteomics 
Molecular Analysis 
X 
Telephone Follow Upm 
X 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: CMS-005 Amendment 2 
APPENDIX 2. SPONSOR SIGNATURE 
Study Title: 
Phase I Study of Ad5 [El-, E2b-]-HER2/neu Vaccine (ETBX-021) 
in Subjects with Unresectable Locally Advanced or Metastatic 
HER2-Low-Expressing (IHC 1 +/2+) Breast Cancer 
Study Number: 
CMS-005, Amendment 2 
Final Date: 
25 May 2016 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
Signed: 
Chief Medical Officer 
Medical and Safety Monitor 
NantBioScience, Inc. 
Confidential and Proprietary 
Page 76 
Date: 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
1 
TITLE PAGE 
PROTOCOL NUMBER QUILT-3.013 (CMS-005) 
PHASE 1 STUDY OF AD5 [E1-, E2B-]-HER2/NEU 
VACCINE (ETBX-021) IN SUBJECTS WITH 
UNRESECTABLE LOCALLY ADVANCED OR 
METASTATIC HER2-EXPRESSING (IHC 1+/2+/3+) 
CANCER 
IND Number: 
016,871 
Clinical Study Sponsor: 
NantBioScience, Inc. 
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 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Jim Farmer 
Senior Director, Clinical Operations 
NantKwest, Inc 
Email: Jim.Farmer@Nantkwest.com 
Office Phone: 310-853-7522 
SAE Reporting: 
Submit SAE Reports to one of the following: 
SAE Email: SAE.Reporting@NantBio.com 
Fax: 800-853-3497 
 
Protocol Version 
Date 
Original Protocol CMS-005 
26 February 2016 
Protocol CMS-005 Amendment 1 
20 April 2016 
Protocol CMS-005 Amendment 2 
25 May 2016 
Protocol QUILT-3.013 (CMS-005) 
Amendment 3 
22 February 2018 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
2 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantBioScience, Inc. 
Name of Investigational Product: 
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection (ETBX-021) 
Name of Active Ingredient: 
Ad5 [E1-, E2b-]-HER2/neu 
Title of Study:  
Phase 1 Study of Ad5 [E1-, E2b-]-HER2/neu Vaccine (ETBX-021) in Subjects with Unresectable 
Locally Advanced or Metastatic HER2-Expressing (IHC 1+/2+/3+) Cancer 
Study Number: 
QUILT-3.013 (formerly CMS-005) 
Study Phase: 
Phase 1 
Primary Objectives: 
• 
Determine the overall safety and recommended phase 2 dose of ETBX-021 when administered 
subcutaneously (SC) every 3 weeks for three injections followed by three booster injections at 
3-month intervals to subjects with HER2-expressing cancer. 
Secondary Objectives: 
• 
Make preliminary assessments of objective response rate (ORR), disease control rate (DCR), 
duration of response, progression-free survival (PFS), and overall survival (OS) in subjects 
with HER2-expressing cancer treated with ETBX-021. 
Exploratory Objectives: 
• 
Evaluate the immunogenicity of ETBX-021 and determine the genomic and proteomic profile 
of subjects’ tumors to identify gene mutations, gene amplifications, RNA-expression levels, 
and protein-expression levels. Correlations between genomic/proteomic profiles and efficacy 
outcomes will be assessed. 
Primary Endpoints: 
• 
Dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or highest tested dose 
(HTD). 
• 
Treatment-emergent adverse event (AEs) and serious adverse events (SAEs). 
• 
Clinically significant changes in safety laboratory tests, physical examinations, 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF), and vital signs. 
Secondary Endpoints: 
• 
ORR (confirmed complete or partial response) according to the Response Evaluation Criteria 
in Solid Tumors (RECIST) Version 1.1. 
• 
DCR (confirmed response or stable disease lasting for at least 6 months). 
• 
Duration of response. 
• 
PFS. 
• 
OS. 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
3 
Exploratory Endpoints: 
• 
Immunogenicity of ETBX-021 by flow cytometric analysis of T-cell frequency, activation 
status, cytokine profiles, and antibody levels.  
• 
Genetic and proteomic profiling and correlations with efficacy. 
Study Design: 
This is a phase 1 trial in subjects with unresectable locally advanced or metastatic HER2-expressing 
(IHC 1+, 2+, or 3+) cancer. The study will be conducted in two parts: the first part will involve dose 
escalation using a 3 + 3 design, and the second part will involve the expansion of the MTD or HTD to 
further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 3 to 6 subjects will 
be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for dose-limiting toxicities 
(DLTs). 
• 
Cohort 1: 5 × 1010 virus particles (VP). 
• 
Cohort 2: 5 × 1011 VP. 
• 
If needed, dose de-escalation cohort (cohort -1): 5 × 109 VP. 
Dose expansion will occur when the MTD or HTD has been determined. An additional 12 subjects will 
be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD or HTD. 
Enrollment (planned): 
Up to 30 subjects will be enrolled in the study. In the dose escalation component, 3 to 6 subjects will be 
sequentially enrolled starting at cohort 1. In the dose expansion component (ie, once the MTD or HTD 
has been identified), an additional 12 subjects will be enrolled for a total of 18 subjects in the 
MTD/HTD cohort to obtain further safety, preliminary efficacy, and immunogenicity data.  
Diagnosis and Main Criteria for Inclusion: 
Subjects must have histologically confirmed unresectable locally advanced or metastatic cancer that 
expresses HER2 (IHC 1+, 2+, or 3+).  
Investigational Product, Dosage, and Mode of Administration:  
ETBX-021 (5 × 109, 5 × 1010, or 5 × 1011 VP in 1.0 mL) will be administered by SC injection every 
3 weeks for 3 injections, followed by 3 booster injections at 3-month intervals. 
Duration of Treatment:  
Subjects will receive treatment for up to 42 weeks (injections at 0, 3, and 6 weeks with booster 
injections at 18, 30, and 42 weeks) or until they experience progressive disease or unacceptable 
toxicity, withdraw consent, or if the Investigator feels it is no longer in their best interest to continue 
treatment. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Criteria for Evaluation: 
Safety: Safety endpoints include assessments of DLT, MTD or HTD, treatment-emergent AEs, SAEs, 
and clinically significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and 
vital signs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response (ORR and DCR) will be evaluated according to RECIST Version 1.1; 
duration of response, PFS, and OS will also be evaluated. 
Exploratory Immune Analysis: Immune responses will be detected and quantified in flow cytometry-
based and serum assays. 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
4 
 
Exploratory Molecular Profiling, Analysis, and Rationale: Genomic sequencing of tumor cells from 
tissue relative to non-tumor cells from whole blood will be profiled to identify the genomic variances 
that may contribute to response or disease progression and provide an understanding of molecular 
abnormalities. RNA sequencing will be conducted to provide expression data and give relevance to 
DNA mutations. Quantitative proteomics analysis will be conducted to determine the exact amounts of 
specific proteins and to confirm expression of genes that are correlative of response to vaccine 
immunotherapy and disease progression. All genomic, transcriptomic, and proteomic molecular 
analyses will be retrospective and exploratory. 
Statistical Methods: 
The rate of DLTs and the MTD or HTD will be assessed. Overall safety will be assessed by descriptive 
analyses using tabulated frequencies of AEs by grade using CTCAE Version 4.03 within dose cohorts 
and for the overall study population in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and vital signs. 
ORR and DCR will be evaluated according to RECIST Version 1.1 by dose cohort and overall; 
duration of response will also be evaluated. PFS and OS will be analyzed using Kaplan-Meier methods 
by dose cohort and overall. 

 
ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
24 
Figure 1: 
Study Design and Treatment Schema 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
 
Confidential and Proprietary 
35 
Table 3: 
Time and Events Schedule 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1 
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
 
 
Clinic Visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Heighta, 
Weight, ECOG 
Xb 
Xb 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Medical Historyc 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm HER2 Expressiond 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signse 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
12-Lead ECG 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Echocardiogram/MUGAf 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Confirm Contraceptive Measuresg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Injection/ Injection 
Site Reaction Monitoringh 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Dispensation of Subject Diary 
Cardi 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
Confidential and Proprietary 
36 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
Review of Subject Diary Cardi 
X 
X 
X 
X 
X 
X 
X 
Telephone Contact 72 Hours Post 
Injection 
X 
X 
X 
X 
X 
X 
Tumor Imagingj 
X 
X 
X 
X 
X 
X 
Pregnancy Testk 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Chemistry Panel 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
CBC, Differential, Platelets 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
Serum Virology (HIV, HBV, 
HCV)l 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Immune Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Genomics, 
Transcriptomics, and Proteomics 
Molecular Analysis 
X 
Telephone Follow Upm 
X 

ETBX-021 
NantBioScience, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 3 
APPENDIX 2. 
SPONSOR SIGNATURE 
Study Title: 
Phase l Study of Ad5 [El-, E2b-]-HER2/neu Vaccine (ETBX-
021) in Subjects with Unresectable Locally Advanced or 
Metastatic HER2-expressing (IHC l +/2+/3+) Cancer 
Study Number: 
QUILT-3.013 (CMS-005), Amendment 3 
Final Date: 
22 February 2018 
This clinical study protocol was subject to critical review and has been approved by 
NantBioScience, Inc. The fo 
wing personnel contributed to writing and/or approving this 
protocol: 
.Lee, MD 
nior Vice President Adult Medical Affairs, 
NantKwest Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: John.Lee@Nantkwest.com 
Cell Phone:+ 1-605-610-6391 
Confidential and Proprietary 
76 
Date: 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
1 
TITLE PAGE 
PROTOCOL NUMBER QUILT-3.013 (CMS-005) 
PHASE 1 STUDY OF AD5 [E1-, E2B-]-HER2/NEU 
VACCINE (ETBX-021) IN SUBJECTS WITH 
UNRESECTABLE LOCALLY ADVANCED OR 
METASTATIC HER2-EXPRESSING (IHC 1+/2+/3+) 
CANCER 
IND Number: 
016,871 
Clinical Study Sponsor: 
NantBio, Inc. 
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 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Jim Farmer 
Senior Director, Clinical Operations 
NantKwest, Inc 
Email: Jim.Farmer@Nantkwest.com 
Office Phone: 310-853-7522 
SAE Reporting: 
Submit SAE Reports to one of the following: 
SAE Email: SAE.Reporting@NantBio.com 
Fax: 800-853-3497 
 
Protocol Version 
Date 
Original Protocol CMS-005 
26 February 2016 
Protocol CMS-005 Amendment 1 
20 April 2016 
Protocol CMS-005 Amendment 2 
25 May 2016 
Protocol QUILT-3.013 (CMS-005) 
Amendment 3 
22 February 2018 
Protocol QUILT-3.013 (CMS-005) 
Amendment 4 
1 May 2018 
 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
2 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
NantBio, Inc. 
Name of Investigational Product: 
Ad5 [E1-, E2b-]-HER2/neu Vaccine, Suspension for Injection (ETBX-021) 
Name of Active Ingredient: 
Ad5 [E1-, E2b-]-HER2/neu 
Title of Study:  
Phase 1 Study of Ad5 [E1-, E2b-]-HER2/neu Vaccine (ETBX-021) in Subjects with Unresectable 
Locally Advanced or Metastatic HER2-Expressing (IHC 1+/2+/3+) Cancer 
Study Number: 
QUILT-3.013 (formerly CMS-005) 
Study Phase: 
Phase 1 
Primary Objectives: 
• 
Determine the overall safety and recommended phase 2 dose of ETBX-021 when administered 
subcutaneously (SC) every 3 weeks for three injections followed by three booster injections at 
3-month intervals to subjects with HER2-expressing cancer. 
Secondary Objectives: 
• 
Make preliminary assessments of objective response rate (ORR), disease control rate (DCR), 
duration of response, progression-free survival (PFS), and overall survival (OS) in subjects 
with HER2-expressing cancer treated with ETBX-021. 
Exploratory Objectives: 
• 
Evaluate the immunogenicity of ETBX-021 and determine the genomic and proteomic profile 
of subjects’ tumors to identify gene mutations, gene amplifications, RNA-expression levels, 
and protein-expression levels. Correlations between genomic/proteomic profiles and efficacy 
outcomes will be assessed. 
Primary Endpoints: 
• 
Dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or highest tested dose 
(HTD). 
• 
Treatment-emergent adverse event (AEs) and serious adverse events (SAEs). 
• 
Clinically significant changes in safety laboratory tests, physical examinations, 
electrocardiograms (ECGs), left ventricular ejection fraction (LVEF), and vital signs. 
Secondary Endpoints: 
• 
ORR (confirmed complete or partial response) according to the Response Evaluation Criteria 
in Solid Tumors (RECIST) Version 1.1. 
• 
DCR (confirmed response or stable disease lasting for at least 6 months). 
• 
Duration of response. 
• 
PFS. 
• 
OS. 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
3 
Exploratory Endpoints: 
• 
Immunogenicity of ETBX-021 by flow cytometric analysis of T-cell frequency, activation 
status, cytokine profiles, and antibody levels.  
• 
Genetic and proteomic profiling and correlations with efficacy. 
Study Design: 
This is a phase 1 trial in subjects with unresectable locally advanced or metastatic HER2-expressing 
(IHC 1+, 2+, or 3+) cancer. The study will be conducted in two parts: the first part will involve dose 
escalation using a 3 + 3 design, and the second part will involve the expansion of the MTD or HTD to 
further evaluate safety, preliminary efficacy, and immunogenicity. In the first part, 3 to 6 subjects will 
be sequentially enrolled starting at dose cohort 1. Subjects will be assessed for dose-limiting toxicities 
(DLTs). 
• 
Cohort 1: 5 × 1010 virus particles (VP). 
• 
Cohort 2: 5 × 1011 VP. 
• 
If needed, dose de-escalation cohort (cohort -1): 5 × 109 VP. 
Dose expansion will occur when the MTD or HTD has been determined. An additional 12 subjects will 
be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD or HTD. 
Enrollment (planned): 
Up to 30 subjects will be enrolled in the study. In the dose escalation component, 3 to 6 subjects will be 
sequentially enrolled starting at cohort 1. In the dose expansion component (ie, once the MTD or HTD 
has been identified), an additional 12 subjects will be enrolled for a total of 18 subjects in the 
MTD/HTD cohort to obtain further safety, preliminary efficacy, and immunogenicity data.  
Diagnosis and Main Criteria for Inclusion: 
Subjects must have histologically confirmed unresectable locally advanced or metastatic cancer that 
expresses HER2 (IHC 1+, 2+, or 3+). For malignancies other than breast and gastrointestinal, HER2 
expression must be confirmed by a validated in situ hybridization (ISH) assay with results considered 
positive of HER2 amplification by ASCO/CAP HER2 testing guideline. 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-021 (5 × 109, 5 × 1010, or 5 × 1011 VP in 1.0 mL) will be administered by SC injection every 
3 weeks for 3 injections, followed by 3 booster injections at 3-month intervals. 
Duration of Treatment:  
Subjects will receive treatment for up to 42 weeks (injections at 0, 3, and 6 weeks with booster 
injections at 18, 30, and 42 weeks) or until they experience progressive disease or unacceptable 
toxicity, withdraw consent, or if the Investigator feels it is no longer in their best interest to continue 
treatment. 
Reference Therapy, Dosage, and Mode of Administration:  
Not applicable. 
Criteria for Evaluation: 
Safety: Safety endpoints include assessments of DLT, MTD or HTD, treatment-emergent AEs, SAEs, 
and clinically significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and 
vital signs. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response (ORR and DCR) will be evaluated according to RECIST Version 1.1; 
duration of response, PFS, and OS will also be evaluated. 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
4 
Exploratory Immune Analysis: Immune responses will be detected and quantified in flow cytometry-
based and serum assays. 
Exploratory Molecular Profiling, Analysis, and Rationale: Genomic sequencing of tumor cells from 
tissue relative to non-tumor cells from whole blood will be profiled to identify the genomic variances 
that may contribute to response or disease progression and provide an understanding of molecular 
abnormalities. RNA sequencing will be conducted to provide expression data and give relevance to 
DNA mutations. Quantitative proteomics analysis will be conducted to determine the exact amounts of 
specific proteins and to confirm expression of genes that are correlative of response to vaccine 
immunotherapy and disease progression. All genomic, transcriptomic, and proteomic molecular 
analyses will be retrospective and exploratory. 
Statistical Methods: 
The rate of DLTs and the MTD or HTD will be assessed. Overall safety will be assessed by descriptive 
analyses using tabulated frequencies of AEs by grade using CTCAE Version 4.03 within dose cohorts 
and for the overall study population in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, LVEF, and vital signs. 
ORR and DCR will be evaluated according to RECIST Version 1.1 by dose cohort and overall; 
duration of response will also be evaluated. PFS and OS will be analyzed using Kaplan-Meier methods 
by dose cohort and overall. 

 
ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
24 
Figure 1: 
Study Design and Treatment Schema 
 
 
 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
 
Confidential and Proprietary 
35 
Table 3: 
Time and Events Schedule 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1 
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
 
 
Clinic Visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, Heighta, 
Weight, ECOG 
Xb 
Xb 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Medical Historyc 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm HER2 Expressiond 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signse 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
12-Lead ECG 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Echocardiogram/MUGAf 
X 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Confirm Contraceptive Measuresg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Injection/ Injection 
Site Reaction Monitoringh 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
Dispensation of Subject Diary 
Cardi 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3.013 (CMS-005) Amendment 4 
Confidential and Proprietary 
36 
Assessment 
Screening 
Treatment 
(Every 3-Week Dosing) 
Boosters 
(Every 3-Month Dosing) 
End 
of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day 
-28 to -1
Baseline/
0 
3 
6 
9 
18 
21 
30 
33 
42 
45 
Review of Subject Diary Cardi 
X 
X 
X 
X 
X 
X 
X 
Telephone Contact 72 Hours Post 
Injection 
X 
X 
X 
X 
X 
X 
Tumor Imagingj 
X 
X 
X 
X 
X 
X 
Pregnancy Testk 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Chemistry Panel 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
CBC, Differential, Platelets 
Xb 
Xb 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
Serum Virology (HIV, HBV, 
HCV)l 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Immune Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Genomics, 
Transcriptomics, and Proteomics 
Molecular Analysis 
X 
Telephone Follow Upm 
X 

ETBX-021 
NantBio, Inc. 
Clinical Trial Protocol: QUILT-3 .013 (CMS-005) Amendment 4 
APPENDIX 2. 
SPONSOR SIGNATURE 
Study Title: 
Phase 1 Study of Ad5 [El-, E2b-]-HER2/neu Vaccine (ETBX-021) in 
Subjects with Unresectable Locally Advanced or Metastatic HER2-
expressing (IHC l +/2+/3+) Cancer 
Study Number: 
QUILT-3.013 (CMS-005), Amendment 4 
Final Date: 
1May2018 
This clinical study protocol was subject to critical review and has been approved by NantBio, 
Inc. The following p©r onnel 
ntribut d to writing and/or approving this protocol: 
.Lee, MD 
nior Vice President Adult Medical Affairs, 
antK west Inc. 
9920 Jefferson Blvd 
Culver City, CA 90232 
Email: J ohn.Lee@Nantkwest.com 
Cell Phone: +1-605-610-6391 
Confidential and Proprietary 
76 
Date: YJ-/(j