Phase 1b/2 Study of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination With ALT-803 (Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer
Phase: PHASE1
Conditions: Thyroid Cancer, Colon Cancer, Ovarian Cancer, Breast Cancer, Lung Cancer, Pancreatic Cancer
Sponsor: NantCell, Inc.

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 1 
Phase 1b/2 Study of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) 
Vaccine in Combination With ALT-803 (Super-agonist IL-
15) in Subjects Having CEA-Expressing Cancer.
Protocol Number: 
QUILT-3.03X 
Principal Investigator: 
Michael Morse, MD 
Duke University Medical Center 
200 Trent Dr. 
Durham, NC 27710 
Email: morse004@mc.duke.edu 
Office Phone: 919-681-3480 
Principal Research Investigator 
Jeffrey Schlom, PhD 
Center for Cancer Research 
National Cancer Institute 
Building 10, Room 8B09 
Bethesda, MD 20892-1750 
Email: js141@nih.gov 
Office Phone: 301-496-4343 
IND Sponsor: 
Etubics Corporation 
410 West Harrison Suite 100 
Seattle, WA 98119Office  
Phone: 206-838-5110 
Funded by: 
Etubics Corporation 
410 West Harrison Suite 100 
Email: frank@etubics.com 
Office Phone:  206-838-5110 
Sponsor Contact: 
(For medical questions/emergencies) 
John Lee, MD 
9920 Jefferson Boulevard 
Culver City, CA 90232 
Email: John.Lee@nantkwest.com 
Office Phone: 605-610-6391 
Mobile Phone: 605-610-6391 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Elizabeth S. Gabitzsch 
Etubics Corporation 
410 West Harrison Suite 100 
Seattle, WA 98119Email: beth@etubics.com 
Office Phone: 206-838-5110 Ext 103 
Email: beth@etubics.com 
Amy Rock, PhD.  
Altor BioScience 
28 North Commerce Parkway 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 2 
Miramac, FL 33025 
Office Phone: 954-443-8600 
Email: AmyRock@altorbioscience.com 
Protocol Version 
Date 
QUILT-3.03X 
6 December, 2016 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 3 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with United 
States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 
CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical principles outlined in 
the Declaration of Helsinki.  The study will receive approval from an Institutional Review Board 
(IRB) prior to commencement.  The Principal Investigator will assure that no deviation from, or 
changes to the protocol will take place without prior agreement from Etubics Corporation 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: Michael Morse, MD 
Signed: _____________________________________ Date: ______________ 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 4 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
Etubics Corporation 
Name of Investigational Product: 
A combination of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) vaccine and ALT-803 (Super-agonist IL-
15) 
Name of Active Ingredient: 
ETBX-011: Ad5 [E1-, E2b-]-CEA(6D) 
ALT-803: IL-15N72D:IL-15RαSu/IgG1 Fc complex (Superagonist IL-15) 
Title of Study:  
Phase 1b/2 Study of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination with ALT-803 
(Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer 
Study Number: 
QUILT-3.03X 
Study Phase: 
Phase 1b/2 
Study Objectives: 
Primary Objectives 
Phase 1b 

Determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the
ETBX-011 plus ALT-803 combination treatment in subjects with carcinoembryonic antigen
(CEA)-expressing cancers whose tumor has recurred after standard-of-care treatment
Phase 2 

Determine the overall safety and tolerability profile for the MTD dose of the ETBX-011 plus
ALT-803 combination treatment in subjects with CEA expressing cancers whose tumor has
recurred after standard-of-care treatment.

Preliminary evaluation of the overall response rate (ORR) for the MTD dose of the ETBX-011
plus ALT-803 combination treatment in the following indications known to express CEA:
1.
Histologically confirmed unresectable locally advanced or metastatic medullary thyroid
cancer that expresses CEA and have progressed on at least cabozantinib or vandetanib.
2.
Histologically confirmed unresectable locally advanced or metastatic colon cancer that
expresses CEA and have progressed on at least one prior standard-of-care treatment with a
FOLFIRI- or FOLFOX-based combination therapy.
3.
Histologically confirmed unresectable locally advanced or metastatic ovarian cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based
combination therapy.
4.
Histologically confirmed unresectable locally advanced or metastatic breast cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based
combination therapy.

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 5 
5.
Histologically confirmed unresectable locally advanced or metastatic lung cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based
combination therapy.
6.
Histologically confirmed unresectable locally advanced or metastatic pancreatic cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based
combination therapy.
7.
Other histologically confirmed unresectable locally advanced or metastatic cancers that
express CEA and have progressed on at least one prior standard-of-care–based combination
therapy.
Secondary Objectives 

Preliminary evaluation of duration of response,  progression-free survival (PFS), and overall
survival (OS) for the MTD dose of the ETBX-011 plus ALT-803 combination treatment in the
indications outlined above.
Exploratory Objectives 

Evaluate the immunogenicity against CEA over the course of treatment with combined ETBX-
011 plus ALT-803

To determine the genomic, transcriptomic, and proteomic profile of subjects’ tumors to identify
gene mutations, gene amplifications, RNA-expression levels, and protein-expression levels.
Correlations between genomic, transcriptomic, and proteomic profiles and efficacy outcome
will be assessed.
Study Design: 
This is a phase 1b/2, open-label, multicenter, dose-escalation study of ETBX-011 vaccine used in 
combination with ALT-803 in subjects with previously treated locally advanced or metastatic CEA-
expressing cancer. 
The trial will consist of a phase 1b study with of ETBX-011 as a fixed dose with a dose escalation of 
ALT-803 unless de-escalation is required. The proposed phase 2 expansion study will give additional 
safety data for the MTD as well as preliminary efficacy data in several indications known to express 
CEA.  
The studies will be conducted in conformity with Good Clinical Practice. 
The study will involve a previously determined safe dose of ETBX-011 (5 × 1011 virus particles 
[VP]/dose). In the phase 1b study, the ALT-803 dose will be escalated using the standard 3 + 3 design.  
The dose levels will be: 

Level 1: ETBX-011 (5 × 1011 VP/dose) and ALT-803 (10 µg/kg/dose).

Level 2: ETBX-011 (5 × 1011 VP/dose) and ALT-803 (15 µg/kg/dose).

If needed, dose de-escalation of ETBX-011 will be used (1 × 1011 VP/dose).

If needed, dose de-escalation of ALT-803 will be used (6 µg/kg/dose).
In the phase 2 study, subjects from several indications known to express CEA will be treated at the 
MTD. 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 6 
Primary Endpoints: 
Phase 1b 

DLTs

MTD
Phase 2 

Treatment-emergent adverse events (AEs) and serious adverse events (SAEs), clinically
significant changes in safety laboratory tests, physical examinations, electrocardiograms
(ECGs), and vital signs.

ORR
Secondary Endpoints: 

Duration of response

PFS

OS
Exploratory Endpoints: 

Immunogenicity of ETBX-011 by flow cytometric and ELISpot analysis of T-cell frequency,
activation status, cytokine profiles, and CEA antibody, adenovirus antibody levels, and
potential antibody development against the IL-15N72D:IL-15RαSu/IgG1 Fc complex

Genomic, transcriptomic, and proteomic profiles and correlations with efficacy
Enrollment (planned): 
It is expected that up to 12 subjects will be enrolled in the phase 1b study with 3 to 6 subjects 
sequentially enrolled starting at dose level 1. In the phase 2 study, up to 20 subjects for each indication 
will be enrolled and treated at the MTD determined in phase 1b. Subjects from the phase 1b study who 
were treated at the MTD will be included in the phase 2 enrollment targets. 
Diagnosis and Main Criteria for Inclusion: 
Subjects must be diagnosed with one of the following indications: 
1.
Histologically confirmed unresectable locally advanced or metastatic medullary thyroid cancer
that expresses CEA and have progressed on at least cabozantinib or vandetanib.
2.
Histologically confirmed unresectable locally advanced or metastatic colorectal cancer that
expresses CEA and have progressed on at least one prior standard of care treatment with a
FOLFIRI- or FOLFOX-based combination therapy.
3.
Histologically confirmed unresectable locally advanced or metastatic ovarian cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based combination
therapy.
4.
Histologically confirmed unresectable locally advanced or metastatic breast cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based combination
therapy.
5.
Histologically confirmed unresectable locally advanced or metastatic lung cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based combination
therapy.
6.
Histologically confirmed unresectable locally advanced or metastatic pancreatic cancer that
expresses CEA and have progressed on at least one prior standard-of-care–based combination
therapy.

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 7 
7.
Other histologically confirmed unresectable locally advanced or metastatic cancers that express
CEA and have progressed on at least one prior standard-of-care–based combination therapy.
The tumor must express CEA as defined by immunohistochemical staining (at least 50% of the tumor 
with at least moderate intensity of staining) or must be known to be universally CEA positive (ie, colon 
and rectal cancer). 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-011 immunization (5 × 1011 VP/dose in 1.0 mL) will be administered by subcutaneous (SC) 
injection every 3 weeks for 3 injections. 
ALT-803 will be administered by SC injection one week after the ETBX-011, and a second injection 
of ALT-803 will be administered one week after the first. ALT-803 will be administered at a separate 
location from the ETBX-011 immunization site. 
Duration of Treatment: 
Subjects will receive treatment during 3-week cycles for a planned 3 cycles (8 weeks total). Subjects 
will receive treatments unless they experience progressive disease, DLT, withdraw consent, or if the 
investigator determines it is no longer in their best medical interest to continue treatment. 
Evaluation of Endpoints: 
Safety: Safety endpoints include assessments of DLT and MTD, treatment-emergent AE, SAE, and 
clinically significant changes in safety laboratory tests, such as changes in ECG, physical examinations, 
and vital signs. Toxicities will be determined using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response will be determined according to the Response Evaluation Criteria In Solid 
Tumors (RECIST) Version 1.1; duration of response, PFS, and OS will also be evaluated.  
Exploratory Analyses: 
Exploratory Immune Analysis: T-cell immune responses will be detected and quantified by flow 
cytometry and ELISpot. CEA, adenoviral antibody levels, and potential antibody development against 
the IL-15N72D:IL-15RαSu/IgG1 Fc complex will be determined by enzyme-linked immunosorbent 
assay (ELISA). 
Molecular Profiling and Analysis: Genomic sequencing of tumor cells from tissue relative to non-
tumor cells from whole blood will be profiled to identify the genomic variances that may contribute to 
response or disease progression and provide an understanding of molecular abnormalities. RNA 
sequencing will be conducted to provide expression data and give relevance to DNA mutations. 
Quantitative proteomics analysis will be conducted to determine the exact amounts of specific proteins 
and to confirm expression of genes that are correlative of response and disease progression. All 
genomic, transcriptomic, and proteomic molecular analyses will be retrospective and exploratory. 
Statistical Methods: 
Overall safety and tolerability will be assessed by descriptive analyses using tabulated frequencies of 
AEs by grade using CTCAE Version 4.03  in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, and vital signs. Tumor 
response will be evaluated according to RECIST Version 1.1; duration of response will also be 
evaluated. PFS and OS will be analyzed using Kaplan-Meier methods. 
Phase 1b data will be presented by dose level for all indications combined. Phase 2 data will be 
presented separately for each indication. 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
 
Confidential and Proprietary 
Page 8 
In the phase 2 study, up to 20 subjects for each indication will be enrolled and treated at the MTD 
determined in phase Ib. Assuming a 5% ORR, a sample size of 20 subjects will provide a 95% 
confidence interval of ORR from 0 to 15%. 
Immune responses assessed in ELISpot, flow cytometry, and ELISA tests will be analyzed employing 
statistical methods as described in Section 8.1.3 . 
 
 
 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 52 
Table 5: 
Time and Events Schedule 
Assessment 
Screening 
Treatment (Every 3-Week Vaccine Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day -28 to -1 Baseline/0
1 
2 
3 
4 
5 
6 
7 
8 
Clinic Visit 
X 
X 
X
X
X
X
X
X 
X 
X 
X 
ETBX-011 Vaccine 
X 
X
X 
ALT-803 
X
X
X
X
X 
X 
CT scan Imaging 
X 
X 
Informed Consent 
X 
Inclusion/Exclusion 
X 
Demographics 
X 
Physical Examination, 
Heighta, Weight, ECOG 
Xb
Xb 
 
 
X
 
 
X 
X 
Medical Historyc 
X 
X 
Obtain biopsy for CEA 
Expression and genomic 
testing 
X 
X 
Confirm CEA Expressiond 
X 
Concomitant Medications 
X 
X 
X
X 
X 
Vital Signse 
X 
X 
X
X
X
X
X
X 
X 
X 
X 
12-Lead ECG
X 
 
 
X
 
 
X 
X 
Confirm Contraceptive 
Measuresg 
X 
Study Drug Injection/ 
Injection Site Reaction 
Monitoringh 
X 
X
X
X
X
X
X 
X 
X 
X 
Dispensation of Subject 
Diary Cardi 
X 
 
 
X
 
 
X 
Review of Subject Diary 
Cardi 
X
X
X
X
X
X 
X 
X 
X 
Telephone Contact 72 
Hours Post Injection 
X 
X
X
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 
X 
X 

ETBX-011 and ALT-803 
Etubics Corporation. 
Clinical Trial Protocol:  QUILT-3.03X 
Confidential and Proprietary 
Page 53 
Assessment 
Screening 
Treatment (Every 3-Week Vaccine Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day -28 to -1 Baseline/0
1 
2 
3 
4 
5 
6 
7 
8 
CBC, Differential, Platelets 
Xb
Xb 
X
X
X
X
X
X 
X 
X 
X 
CEA level 
X 
X 
X
X 
X 
Coagulation 
X 
 
 
X
 
 
X 
X 
Serum Virology (HIV, 
HBV, HCV)l 
X 
X 
Adverse Events 
X 
X
X
X
X
X
X 
X 
X 
X 
Exploratory Immune 
Analysis 
X 
 
 
X
 
 
X 
X 
Telephone Follow Upm 
X 
a Height will only be assessed at screening. 
b If the assessment is performed within 24 hours prior to the first dosing, a second assessment at baseline/week 0 can 
be omitted. 
c Complete medical history will be evaluated at screening and includes current and past cardiac and pulmonary history, 
documentation of diagnosis including history of current and prior cancers, prior treatment(s), and prior radiologic 
studies. Any new events in the medical history will be evaluated at baseline. 
d Confirmation of CEA expression by IHC, derived from the most recent metastatic biopsy sample available. Genomic 
testing will also be performed. 
e Vital signs include temperature, heart rate, blood pressure, and respiratory rate. Vital sign assessments are to be 
obtained after the subject has been in a seated resting position for at least 5 minutes. For the first injection, vital signs 
must be assessed 30 and 60 minutes after the injection. Vital signs must be assessed 30 minutes after the subsequent 
injections. 
g Acceptable contraceptive measures are described in Section 4.1.  
h Injection site reactions will be monitored, as described in Section 6.6.1. 
i Subjects will be given a diary card for the self-evaluation and reporting of injection site reactions, as described in - 
j All baseline tumor measurements should be performed based on the subject’s qualifying scan obtained within 28 
days prior to the start of treatment. Tumor imaging and assessments will be performed as described in Section 6.7.2.  
k Serum pregnancy test will be performed on females of childbearing-potential and women < 12 months since the 
onset of menopause. The pregnancy test will be performed at each dosing visit with the result confirmed as negative 
prior to dosing. 
l Serum virology test for HIV (as determined by ELISA and confirmed by western blot), and HBV and HCV (as
determined by HBsAg and hepatitis C serology).
m After the subject completes or withdraws from the study, the study team will contact the subject approximately every
3 months for 12 months and then approximately every 6 months thereafter for 12 months to collect follow-up
information, including survival status (as described in Section 6.7.1.) and any current cancer treatment regimen.

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
PHASE 1B/2 STUDY OF ETBX-011 (AD5 [E1-, E2B-]-
CEA(6D)) VACCINE IN COMBINATION WITH ALT-803 
(SUPER-AGONIST IL-15) IN SUBJECTS HAVING CEA-
EXPRESSING CANCER. 
 
Protocol Number: 
QUILT-3.040 
Principal Investigator: 
Michael Morse, MD 
Duke University Medical Center 
200 Trent Dr. 
Durham, NC 27710 
Email: morse004@mc.duke.edu 
Office Phone: 919-681-3480 
Principal Research Investigator: 
Jeffrey Schlom, PhD 
Center for Cancer Research 
National Cancer Institute 
Building 10, Room 8B09 
Bethesda, MD 20892-1750 
Email: js141@nih.gov 
Office Phone: 301-496-4343 
IND Sponsor: 
Etubics Corporation, a Wholly-Owned 
Subsidiary of NantCell, Inc. 
410 West Harrison Suite 200 
Seattle, WA 98119Office  
Phone: 206-838-5110 
Sponsor Contact: 
(For medical questions/emergencies) 
John Lee, MD 
9920 Jefferson Boulevard 
Culver City, CA 90232 
Email: John.Lee@nantkwest.com 
Office Phone: 605-610-6391 
Mobile Phone: 605-610-6391 
Sponsor Contact:  
(For study administration, operations, and 
execution questions) 
Elizabeth S. Gabitzsch 
Etubics Corporation 
410 West Harrison Suite 100 
Seattle, WA 98119Email: beth@etubics.com 
Office Phone: 206-838-5110 Ext 103 
Email: beth@etubics.com 
Amy Rock, PhD  
Altor BioScience 
2810 North Commerce Parkway 
Miramar, FL 33025 
Office Phone: 954-443-8600 
Email: AmyRock@altorbioscience.com 
Confidential and Proprietary 
1 

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
Protocol Version 
Date 
QUILT-3.040 
06 December 2016 
QUILT-3.040 Amendment 1  
13 April 2017 
Confidential and Proprietary 
2 

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
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 
Etubics Corporation and documented approval from the IRB, except where necessary to 
eliminate an immediate hazard(s) to the trial participants.   
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.   
 
Principal Investigator:  
 
 
Signed: _____________________________________ Date: ______________ 
Confidential and Proprietary 
3 

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: 
Etubics Corporation, a wholly-owned subsidiary of NantCell, Inc. 
Name of Investigational Product: 
A combination of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) vaccine and ALT-803 (Super-agonist 
IL-15) 
Name of Active Ingredient: 
ETBX-011: Ad5 [E1-, E2b-]-CEA(6D) 
ALT-803: IL-15N72D:IL-15RαSu/IgG1 Fc complex (Superagonist IL-15) 
Title of Study:  
Phase 1b/2 Study of ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination with ALT-803 
(Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer 
Study Number: 
QUILT-3.040 
Study Phase: 
Phase 1b/2 
Study Objectives: 
Primary Objectives 
Phase 1b 
 
Determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the 
ETBX-011 plus ALT-803 combination treatment in subjects with carcinoembryonic antigen 
(CEA)-expressing cancers whose tumor has recurred after standard-of-care treatment 
Phase 2 
 
Determine the overall safety and tolerability profile for the MTD dose of the ETBX-011 plus 
ALT-803 combination treatment in subjects with CEA expressing cancers whose tumor has 
recurred after standard-of-care treatment. 
 
Preliminary evaluation of the overall response rate (ORR) for the MTD dose of the 
ETBX-011 plus ALT-803 combination treatment in the following indications known to 
express CEA: 
1. Histologically confirmed unresectable locally advanced or metastatic medullary thyroid 
cancer that expresses CEA and have progressed on at least cabozantinib or vandetanib. 
2. Histologically confirmed unresectable locally advanced or metastatic colon cancer that 
expresses CEA and have progressed on at least one prior standard-of-care treatment with 
a FOLFIRI- or FOLFOX-based combination therapy. 
3. Histologically confirmed unresectable locally advanced or metastatic ovarian cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based 
combination therapy. 
4. Histologically confirmed unresectable locally advanced or metastatic breast cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based 
combination therapy. 
Confidential and Proprietary 
4 

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
5. Histologically confirmed unresectable locally advanced or metastatic lung cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based 
combination therapy. 
6. Histologically confirmed unresectable locally advanced or metastatic pancreatic cancer 
that expresses CEA and have progressed on at least one prior standard-of-care–based 
combination therapy. 
7. Other histologically confirmed unresectable locally advanced or metastatic cancers that 
express CEA and have progressed on at least one prior standard-of-care–based 
combination therapy. 
Secondary Objectives 
 
Preliminary evaluation of duration of response, progression-free survival (PFS), and overall 
survival (OS) for the MTD dose of the ETBX-011 plus ALT-803 combination treatment in 
the indications outlined above. 
Exploratory Objectives 
 
Evaluate the immunogenicity against CEA over the course of treatment with combined 
ETBX-011 plus ALT-803  
 
Tumor molecular profiles and correlations with safety and efficacy.  
 
To assess changes in circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA) 
using a genomics panel. 
Study Design: 
This is a phase 1b/2, open-label, multicenter, dose-escalation study of ETBX-011 vaccine used in 
combination with ALT-803 in subjects with previously treated locally advanced or metastatic CEA-
expressing cancer. 
The trial will consist of a phase 1b study with of ETBX-011 as a fixed dose with a dose escalation of 
ALT-803 unless de-escalation is required. The proposed phase 2 expansion study will give additional 
safety data for the MTD as well as preliminary efficacy data in several indications known to express 
CEA.  
The studies will be conducted in conformity with Good Clinical Practice.  
The study will involve a previously determined safe dose of ETBX-011 (5 × 1011 virus particles 
[VP]/dose). In the phase 1b study, the ALT-803 dose will be escalated using the standard 3 + 3 
design.  The dose levels will be: 
 
Level 1: ETBX-011 (5 × 1011 VP/dose) and ALT-803 (10 µg/kg/dose). 
 
Level 2: ETBX-011 (5 × 1011 VP/dose) and ALT-803 (15 µg/kg/dose). 
 
If needed, dose de-escalation of ETBX-011 will be used (1 × 1011 VP/dose). 
 
If needed, dose de-escalation of ALT-803 will be used (6 µg/kg/dose). 
In the phase 2 study, subjects from several indications known to express CEA will be treated at the 
MTD. 
Confidential and Proprietary 
5 

ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
Primary Endpoints: 
Phase 1b 
 
DLTs 
 
MTD 
Phase 2 
 
Treatment-emergent adverse events (AEs) and serious adverse events (SAEs), clinically 
significant changes in safety laboratory tests, physical examinations, electrocardiograms 
(ECGs), and vital signs. 
 
ORR 
Secondary Endpoints: 
 
Duration of response 
 
PFS 
 
OS 
Exploratory Endpoints: 
 
Immunogenicity of ETBX-011 by flow cytometric and ELISpot analysis of T-cell frequency, 
activation status, cytokine profiles, and CEA antibody, adenovirus antibody levels, and 
potential antibody development against the IL-15N72D:IL-15RαSu/IgG1 Fc complex  
 
To assess tumor molecular profiles (genomics, transcriptomics, and proteomics) and 
correlations with safety and efficacy outcomes 
 
To assess changes in circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA) 
using a genomics panel. 
Enrollment (planned): 
It is expected that up to 12 subjects will be enrolled in the phase 1b study with 3 to 6 subjects 
sequentially enrolled starting at dose level 1. In the phase 2 study, up to 20 subjects for each 
indication will be enrolled and treated at the MTD determined in phase 1b. Subjects from the phase 
1b study who were treated at the MTD will be included in the phase 2 enrollment targets. 
Diagnosis and Main Criteria for Inclusion: 
Subjects must be diagnosed with one of the following indications: 
1. Histologically confirmed unresectable locally advanced or metastatic medullary thyroid 
cancer that expresses CEA and have progressed on at least cabozantinib or vandetanib. 
2. Histologically confirmed unresectable locally advanced or metastatic colorectal cancer that 
expresses CEA and have progressed on at least one prior standard of care treatment with a 
FOLFIRI- or FOLFOX-based combination therapy. 
3. Histologically confirmed unresectable locally advanced or metastatic ovarian cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based combination 
therapy. 
4. Histologically confirmed unresectable locally advanced or metastatic breast cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based combination 
therapy. 
5. Histologically confirmed unresectable locally advanced or metastatic lung cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based combination 
therapy. 
 
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ETBX-011 and ALT-803 
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Clinical Trial Protocol: QUILT-3.040 
 
6. Histologically confirmed unresectable locally advanced or metastatic pancreatic cancer that 
expresses CEA and have progressed on at least one prior standard-of-care–based combination 
therapy. 
7. Other histologically confirmed unresectable locally advanced or metastatic cancers that 
express CEA and have progressed on at least one prior standard-of-care–based combination 
therapy. 
The tumor must express CEA as defined by immunohistochemical staining (at least 50% of the tumor 
with at least moderate intensity of staining) or must be known to be universally CEA positive 
(ie, colon and rectal cancer). 
Investigational Product, Dosage, and Mode of Administration:  
ETBX-011 immunization (5 × 1011 VP/dose in 1.0 mL) will be administered by subcutaneous (SC) 
injection every 3 weeks for 3 injections. 
ALT-803 will be administered by SC injection one week after the ETBX-011, and a second injection 
of ALT-803 will be administered one week after the first. ALT-803 will be administered at a separate 
location from the ETBX-011 immunization site. 
Duration of Treatment:  
Subjects will receive treatment during 3-week cycles for a planned 3 cycles (8 weeks total). Subjects 
will receive treatments unless they experience progressive disease, DLT, withdraw consent, or if the 
investigator determines it is no longer in their best medical interest to continue treatment. 
Evaluation of Endpoints: 
Safety: Safety endpoints include assessments of DLT and MTD, treatment-emergent AE, SAE, and 
clinically significant changes in safety laboratory tests, such as changes in ECG, physical 
examinations, and vital signs. Toxicities will be determined using the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. 
Efficacy: Tumor response will be determined according to the Response Evaluation Criteria In Solid 
Tumors (RECIST) Version 1.1; duration of response, PFS, and OS will also be evaluated.  
Exploratory Analyses: 
Exploratory Immune Analysis: T-cell immune responses will be detected and quantified by flow 
cytometry and ELISpot. CEA, adenoviral antibody levels, and potential antibody development against 
the IL-15N72D:IL-15RαSu/IgG1 Fc complex will be determined by enzyme-linked immunosorbent 
assay (ELISA). 
Molecular Profiling and Analysis:  Genomic sequencing of tumor cells from tissue relative to non-
tumor cells from whole blood will be profiled to identify the genomic variances that may contribute to 
response or disease progression and provide an understanding of molecular abnormalities.  RNA 
sequencing will be conducted to provide expression data and give relevance to DNA mutations.  
Quantitative proteomics analysis will be conducted to determine the exact amounts of specific 
proteins and to confirm expression of genes that are correlative of response and disease progression. 
All genomic, transcriptomic, and proteomic molecular analyses will be retrospective and exploratory. 
Plasma will be collected and a PCR-based assay will be used to assess expression levels, and directly 
measure fusion genes and mutations in circulating DNA and RNA. 
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ETBX-011 and ALT-803 
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Clinical Trial Protocol: QUILT-3.040 
 
Statistical Methods: 
Overall safety and tolerability will be assessed by descriptive analyses using tabulated frequencies of 
AEs by grade using CTCAE Version 4.03 in terms of treatment-emergent AEs, SAEs, and clinically 
significant changes in safety laboratory tests, physical examinations, ECGs, and vital signs. Tumor 
response will be evaluated according to RECIST Version 1.1; duration of response will also be 
evaluated. PFS and OS will be analyzed using Kaplan-Meier methods. 
Phase 1b data will be presented by dose level for all indications combined. Phase 2 data will be 
presented separately for each indication. 
In the phase 2 study, up to 20 subjects for each indication will be enrolled and treated at the MTD 
determined in phase Ib. Assuming a 5% ORR, a sample size of 20 subjects will provide a 95% 
confidence interval of ORR from 0 to 15%. 
Immune responses assessed in ELISpot, flow cytometry, and ELISA tests will be analyzed employing 
statistical methods as described in Section 8.1.3 . 
 
 
 
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ETBX-011 and ALT-803 
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Clinical Trial Protocol: QUILT-3.040 
 
6. 
STUDY PROCEDURES AND EVALUATIONS 
All required study procedures and evaluations are to be conducted as outlined in this protocol. In 
the event of a deviation from the protocol due to an emergency, accident, or mistake, the 
Investigator or designee must notify the Sponsor as soon as possible. 
All laboratory assessments and evaluations will be performed as described below. 
6.1. 
Time and Events Schedule 
The schedule of study assessments is provided in Table 5. 
Table 5: 
Time and Events Schedule 
Assessment 
Screening 
Treatment (Every 3-Week Vaccine Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day -28 to -1 Baseline/0 
1 
2 
3 
4 
5 
6 
7 
8 
 
 
Clinic Visit 
X 
X 
X X X X X X 
X 
X 
X 
 
ETBX-011 Vaccine 
 
X 
 
 
X  
 
X 
 
 
 
 
ALT-803 
 
 
X X  
X X  
X 
X 
 
 
CT scan Imaging 
X 
 
 
 
 
 
 
 
 
X 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination, 
Heighta, Weight, ECOG 
Xb 
Xb 
 
 
X  
 
X 
 
 
X 
 
Medical Historyc 
X 
X 
 
 
 
 
 
 
 
 
 
 
Obtain biopsy for CEA 
Expression and genomic 
testing (optional for week 8 
sample) 
X 
 
 
 
 
 
 
 
 
X 
 
 
Confirm CEA Expressiond 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
 
 
X  
 
X 
 
 
X 
 
Vital Signse 
X 
X 
X X X X X X 
X 
X 
X 
 
12-Lead ECG 
X 
 
 
 
X  
 
X 
 
 
X 
 
Confirm Contraceptive 
Measuresg 
X 
 
 
 
 
 
 
 
 
 
 
 
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ETBX-011 and ALT-803 
NantCell, Inc. 
Clinical Trial Protocol: QUILT-3.040 
 
Assessment 
Screening 
Treatment (Every 3-Week Vaccine Dosing) 
End of 
Study 
Post 
Study 
Follow 
Up 
Study Week 
Day -28 to -1 Baseline/0 
1 
2 
3 
4 
5 
6 
7 
8 
 
 
Study Drug Injection/ 
Injection Site Reaction 
Monitoringh 
 
X 
X X X X X X 
X 
X 
X 
 
Dispensation of Subject 
Diary Cardi 
 
X 
 
 
X  
 
X 
 
 
 
 
Review of Subject Diary 
Cardi 
 
 
X X X X X X 
X 
X 
X 
 
Telephone Contact 
72 Hours Post Injection 
 
X 
X X 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 
X 
X 
 
CBC, Differential, Platelets 
Xb 
Xb 
X X X X X X 
X 
X 
X 
 
CEA level 
X 
X 
 
 
X  
 
X 
 
 
X 
 
Coagulation 
X 
 
 
 
X  
 
X 
 
 
X 
 
Serum Virology (HIV, 
HBV, HCV)l 
X 
 
 
 
 
 
 
 
 
 
X 
 
Adverse Events 
 
X 
X X X X X X 
X 
X 
X 
 
Exploratory Immune 
Analysis and genomics 
 
X 
 
 
X  
 
X 
 
X 
 
 
Telephone Follow Upm 
 
 
 
 
 
 
 
 
 
 
 
X 
a Height will only be assessed at screening. 
b If the assessment is performed within 24 hours prior to the first dosing, a second assessment at baseline/week 0 can 
be omitted. 
c Complete medical history will be evaluated at screening and includes current and past cardiac and pulmonary 
history, documentation of diagnosis including history of current and prior cancers, prior treatment(s), and prior 
radiologic studies. Any new events in the medical history will be evaluated at baseline. 
d Confirmation of CEA expression by IHC, derived from the most recent metastatic biopsy sample available. 
Genomic testing will also be performed. 
e Vital signs include temperature, heart rate, blood pressure, and respiratory rate. Vital sign assessments are to be 
obtained after the subject has been in a seated resting position for at least 5 minutes. For the first injection, vital 
signs must be assessed 30 and 60 minutes after the injection. Vital signs must be assessed 30 minutes after the 
subsequent injections. 
g Acceptable contraceptive measures are described in Section 4.1. 
h Injection site reactions will be monitored, as described in Section 6.6.1. 
i Subjects will be given a diary card for the self-evaluation and reporting of injection site reactions, as described in 
Appendix 2 and Appendix 3. 
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