A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus Placebo in Combination With Standard of Care Definitive Radiotherapy in Locally Advanced, Unresectable, Chordoma
Phase: PHASE2
Conditions: Chordoma
Sponsor: NantCell, Inc.

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Study number: QUILT-3.011 
CC Protocol #: 15-C-0118  
OSP#: 1407-1336 
Version Date: 30 01 2018 
 
IBC#: RD-15-III-13 
Amendment: G 
NCT Number: NCT02383498 
Title: A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus 
Placebo in Combination with Standard of Care Definitive Radiotherapy in Locally Advanced, 
Unresectable, Chordoma 
NCI Principal Investigator: 
Deric M. Park, M.D., NOB, CCR, NCI A, B, C, D, E, F 
9030 Old Georgetown Road, Bldg. 82 
Bethesda, MD 20892 
Phone: 240-760-6024 
Email: deric.park@nih.gov  
NIH Associate Investigators: 
James Gulley, M.D., Ph.D., GMB, CCR, NCI A, B, C, D, E, F 
Ravi Madan, M.D., GMB, CCR, NCI A, B, C, D, E, F 
DeeDee Smart, M.D., Ph.D., ROB, CCR, NCI A, B, C, D, E, F 
Jennifer Jones, M.D., Ph.D., VB, CCR, NCI A, B, C, D, E, F 
Mark Gilbert M.D, NOB, CCR, NCI A, B, C, D, E, F 
Nancy Garren, MSN, CRNP, NOB, CCR, NCI A, B, C, E, F 
Jing Wu, M.D., NOB, CCR, NCI A, B, C, D, E, F 
Amber Giles, Ph.D., NOB, CCR, NCI E, F 
Christine Bryla, RN, OCD, CCR, NCI A, B, C, E, F 
Ann McCoy, RN, OCD, CCR, NCI A, B, C, E, F 
Jenn Marte, M.D., GMB, CCR, NCI E, F  
Mohammadhadi Bagheri, MD Radiology Dept, CC B, E  
Kathy Warren, M.D., POB, CCR, NCI A, B, C, D, E, F
Kong Y. Chen, Ph.D., NIDDK A, B, E, F
Terri S. Armstrong, Ph.D., ANP-BC, NOB, CCR, NCI A, B, C, D, E, F 
Sonja Crandon, RN, OCD, CCR, NCI A, B, C, E, F
Non-NIH Associate Investigators: Lisa Boris, CRNP, (Contractor) Leidos Biomedical Research, Inc.
A, B, C, D, E, F
Christine Siegel, CRNP, (Contractor) Leidos Biomedical Research, 
Inc. A, B, C, D, E, F 
      Christopher R. Heery, M.D., Bavarian Nordic, Inc. E, F, G 
Alvina Acquaye, MS, (Contractor) Columbus Technologies & 
Services, NOB, CCR, NCI A,B,E,F 
Elizabeth Vera, MS, (Contractor) Columbus Technologies & 
Services, NOB, CCR, NCI A,B,E,F 
Brett Theeler, MD Volunteer/NOB/NCI A,B,C,D,E,F

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
2 
 
 
 
Statistician: 
 
Seth Steinberg, Ph.D. E, F  
 
 
 
 
 
Biostatistics and Data Management Section 
 
 
 
 
Office of the Director, CCR, NCI 
 
 
 
 
 
9609 Medical Center Drive, Room 2W334 
 
 
 
 
 
Rockville, MD 20850 
 
 
 
 
Phone: 240-276-5563  
 
 
 
 
 
Email: Seth.Steinberg@nih.gov 
 
 
 
 
Referral Contact:  
 
Christine Bryla, RN, OCD, CCR, NCI A, B, C, E, F 
 
 
Study Coordinator:  
 
Christine Bryla, RN, OCD, CCR, NCI 
 
 
 
 
 
9030 Old Georgetown Road, Bldg. 82 
 
 
 
 
 
Bethesda, MD 20892 
Phone: 240-760-6007 
Fax: 301-480-2246 
Email: christine.bryla@nih.gov 
 
Sponsor Contact: 
 
 
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 
 
Investigator Roles: 
A. Obtain information by intervening or interacting with living individuals for research purposes 
B. Obtaining identifiable private information about living individuals 
C. Obtaining the voluntary informed consent of individuals to be subjects 
D. Makes decisions about subject eligibility 
E. Studying, interpreting, or analyzing identifiable private information or data/specimens for research 
purposes 
F. Studying, interpreting, or analyzing de-identified data or specimens for research purposes 
G. Some/all research activities performed outside NIH 
 
Investigational Agents:  
Drug Name 
GI-6301 Vaccine (Yeast-Brachyury)  
IND Number 
BB-IND # 14895 
Sponsor 
NantCell, Inc. 
Manufacturer/Supplier 
GlobeImmune 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
3 
 
Commercial Device: wGT3X-BT manufactured by Actigraph. Associate Investigator in the Diabetes, 
Endocrinology, and Obesity Branch of NIDDK will provide the actigraphy equipment. 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
4 
 
PRÉCIS 
Background:  
• Chordoma is a rare disease, affecting about 3,000 people in the United States, with about 
300 new cases diagnosed per year. 
• Brachyury is a member of the T-box family of transcription factors, characterized by a 
highly conserved DNA-binding domain designated as T-domain.   
• Brachyury is expressed universally in chordoma cells. 
• GI-6301 (Yeast-brachyury vaccine) has demonstrated immunogenicity with a tolerable 
and acceptable safety profile in a phase 1 trial. 
• Brachyury specific T cells can lyse human cancer cells expressing brachyury in an MHC 
restricted manner. 
• There have been indications of clinical benefit in patients with chordoma enrolled on the 
phase I trial of GI-6301. 
o 1 Partial Response 
o 1 Mixed Response in Chordoma patients who received Radiation 
o 6 of 9 patients with progressive disease at enrollment had Stable Disease at Day 
85 restaging 
• In vitro, chordoma cell lines are killed significantly better by brachyury-specific T cells 
after radiation exposure using either proton beam or gamma radiation. 
 
Endpoints: 
Primary Objective:  
• To determine if there is a difference in overall response rate (ORR) defined as complete 
response (CR) or partial response (PR) by RECIST 1.1 in the irradiated tumor site after 
up to 24 months among patients with Chordoma who are treated with radiation plus 
vaccine vs. radiation plus placebo. 
 
Eligibility: 
• Patients at least 18 years old with advanced (unresectable, chordoma who are planning to 
be treated with definitive radiotherapy to at least one lesion. 
• No history of autoimmune disease (with exceptions detailed in section 2.1) 
• Measurable disease as defined by RECIST 1.1 
• Adequate organ function 
 
Design: 
• Randomized, double-blind, placebo controlled phase 2 clinical trial of radiation plus 
placebo vs. radiation plus yeast-brachyury vaccine in patients with chordoma. 
• Participants will be randomized on a 1:1 basis to the two arms 
• Participants assigned to the placebo arm will be allowed to cross-over at time of 
confirmed disease progression. 
• Participants who have had a response in the irradiated target lesion and then have 
progression outside of the irradiated site will have the option to receive irradiation or 
other local intervention to the area of disease outside of the radiation field. Progression 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
5 
 
will be determined only by the target lesion which had been irradiated. Other lesions will 
be monitored and intervened upon as clinically necessary. If alternative systemic therapy 
is required, patients would be taken off study at that point. 
• Radiographic progression at the irradiated lesion will be unblinded.  Those who did not 
receive the vaccine will have the option to receive it in combination with radiation to the 
lesion which is demonstrating disease progression.   
• Participants will be evaluated for objective response, and time to progression of the 
irradiated tumor mass as well as overall survival 
• Up to 55 participants will be accrued to the study 
Randomization Schema 
 
Primary endpoint:  Overall response rate (RECIST 1.1) in the irradiated tumor site(s) 
Secondary endpoints: 
-Progression free survival (irradiated tumor), PFS (other sites), overall survival 
-Patient Report Outcomes 
Exploratory endpoints: 
- 
Evaluations of response rate and PFS using other criteria  
- 
(Volumetric, Growth rate kinetics, Choi)  
- 
To evaluate brachyury-specific T cell response pre-, during, and post-treatment. 
- 
To evaluate other parameters of general immune activation detailed in the protocol. 
- 
To evaluate the quantity and quality of tumor infiltrating lymphocytes and other markers 
of local immune response and inflammation pre- and post-treatment in both groups. 
- 
Daily Activity 
Statistical assumption: 
- Goal: improve ORR from 5% to 30% 
 
 
 
 
 
 
 
 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
6 
 
 
Treatment Schema 
 
After C7, study agent doses will be given every 3 months (85 days, -7 / +28 days).  Restaging scans will be 
performed at fixed intervals from the time of completion of radiation: 3 months (-7 / +28 days, corresponds to 
C3D1), 6 months (+/- 4 weeks, corresponds to C6D1), 9 months (+/- 4 weeks, corresponds to C7D1), 12 months (+/- 
4 weeks, corresponds to C8D1), 18 months (+/- 8 weeks, C10D1), 24 months (+/- 8 weeks, C12D1), 36 months (+/- 
8 weeks, C16D1) and yearly thereafter (+/- 8 weeks).  MDASI assessment will take place at baseline and at each 
restaging imaging timepoint. 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: 30 01 2018 
 
61 
 
5 Serum hepatitis B & C antibody should be completed within 12 weeks of initiating treatment. A positive screening test must be 
confirmed by detectable virus in the serum by PCR. 
6 Chemistry panel:  Na+, K+, Cl-, CO2, glucose, BUN, creatinine, albumin, calcium, magnesium, phosphorus, alkaline phosphatase, ALT, 
AST, total bilirubin, TSH, and LDH. 
7 Blood will be obtained for immunologic assays. Research blood will be drawn at baseline and prior to each dose.  2 SST tubes, 6 green 
top tubes are required. 
8 ANA and CD3, 4, 8, 19 subsets will be drawn at baseline and prior to C6 D1. 
9 For patients with questionable history of yeast allergy, this test is performed at the screening visit to detect if the subject has a 
hypersensitivity to Saccharomyces cerevisiae.  A negative response is required for entry into this trial. 
10 In females of child-bearing age, beta-HCG to be done within 48 hours prior to day 1. 
11 Administered subcutaneously at 4 sites.  Dosing will be given as follows: on C1 D1, C1 D15, C1 D29 (all +/-3 days). Dosing will be 
interrupted for the duration of radiation and will resume 14-28 days post radiation depending on patient schedule and any time required 
to recover.  Treatment is then resumed on C2 D1, C2 D15, C2 D29 (all +/- 3 days).  C3 D1 (28 days (+/- 7 days) after C2 D29) begins 
monthly (28 day +/- 7 days) dosing for 4 doses (cycles 3, 4, 5, and 6).  C6 D1 begins every 3 month (85 days -7/+28 days) dosing, 
which goes on for at least 2 years.  After 2 years on study, doses may be given less frequently (every 6-12 months) based on vaccine 
supply and patient preference 
13 Performed in subjects with a questionable history of allergy to yeast 
13 Baseline tissue sample is preferred.  These may be fresh biopsy samples or archived tissue.  If archived tissue, at least 10 unstained 
slides are required.  On-study biopsy specimens will be analyzed by immunohistochemistry for evidence of immune response within the 
tumor.  These samples may be obtained at 6 or 12 months or at evidence of tumor response or tumor progression.  Biopsy is allowable 
for research purposes at other times at investigator discretion with patient consent to biopsy. 
14Post-treatment follow-up labs are not required if the subject prefers to follow-up via phone contact. 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
NantCell Study number: QUILT-3.011 
CC Protocol #: 15-C-0118  
OSP#: 1407-1336 
Version Date: May 14, 2018  
IBC#: RD-15-III-13 
Amendment: H 
NCT Number: NCT02383498 
Title: A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus 
Placebo in Combination with Standard of Care Definitive Radiotherapy in Locally Advanced, 
Unresectable, Chordoma 
NCI Principal Investigator: 
Deric M. Park, M.D., NOB, CCR, NCI A, B, C, D, E, F 
9030 Old Georgetown Road, Bldg. 82 
Bethesda, MD 20892 
Phone: 240-760-6024 
Email: deric.park@nih.gov  
Sponsor Contact: 
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 
Investigational Agents:  
Drug Name 
GI-6301 Vaccine (Yeast-Brachyury) 
IND Number 
BB-IND # 14895 
Sponsor 
NantCell, Inc. 
Manufacturer/Supplier 
GlobeImmune 
Commercial Device: wGT3X-BT manufactured by Actigraph. Associate Investigator in the Diabetes, 
Endocrinology, and Obesity Branch of NIDDK will provide the actigraphy equipment.

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: May 14, 2018 
 
2 
 
STATEMENT OF COMPLIANCE 
This trial will be conducted in accordance with Good Clinical Practice (GCP) as described in the 
International Conference on Harmonization Guideline E6 (ICH E6) and in accordance with 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 312) and the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
Institutional Review Board (IRB) prior to commencement. The Principal Investigator will assure 
that no deviation from or changes to the protocol will take place without prior agreement from 
NantCell and documented approval from the IRB, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator:  
 
Signed: _____________________________________ Date: ______________ 
 
 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: May 14, 2018 
 
3 
 
PRÉCIS 
Background:  
• Chordoma is a rare disease, affecting about 3,000 people in the United States, with about 
300 new cases diagnosed per year. 
• Brachyury is a member of the T-box family of transcription factors, characterized by a 
highly conserved DNA-binding domain designated as T-domain.   
• Brachyury is expressed universally in chordoma cells. 
• GI-6301 (Yeast-brachyury vaccine) has demonstrated immunogenicity with a tolerable 
and acceptable safety profile in a phase 1 trial. 
• Brachyury specific T cells can lyse human cancer cells expressing brachyury in an MHC 
restricted manner. 
• There have been indications of clinical benefit in patients with chordoma enrolled on the 
phase I trial of GI-6301. 
o 1 Partial Response 
o 1 Mixed Response in Chordoma patients who received Radiation 
o 6 of 9 patients with progressive disease at enrollment had Stable Disease at 
Day 85 restaging 
• In vitro, chordoma cell lines are killed significantly better by brachyury-specific T cells 
after radiation exposure using either proton beam or gamma radiation. 
 
Endpoints: 
Primary Objective:  
• To determine if there is a difference in overall response rate (ORR) defined as complete 
response (CR) or partial response (PR) by RECIST 1.1 in the irradiated tumor site after 
up to 24 months among patients with Chordoma who are treated with radiation plus 
vaccine vs. radiation plus placebo. 
 
Eligibility: 
• Patients at least 18 years old with advanced unresectable, chordoma who are planning to 
be treated with definitive radiotherapy to at least one lesion. 
• No history of autoimmune disease (with exceptions detailed in section 2.1) 
• Measurable disease as defined by RECIST 1.1 
• Adequate organ function 
 
Design: 
• Randomized, double-blind, placebo controlled phase 2 clinical trial of radiation plus 
placebo vs. radiation plus yeast-brachyury vaccine in patients with chordoma. 
• Participants will be randomized on a 1:1 basis to the two arms 
• Participants assigned to the placebo arm will be allowed to cross-over at time of 
confirmed disease progression. 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: May 14, 2018 
 
4 
 
• Participants who have had a response in the irradiated target lesion and then have 
progression outside of the irradiated site will have the option to receive irradiation or 
other local intervention to the area of disease outside of the radiation field. Progression 
will be determined only by the target lesion which had been irradiated. Other lesions will 
be monitored and intervened upon as clinically necessary. If alternative systemic therapy 
is required, patients would be taken off study at that point. 
• Radiographic progression at the irradiated lesion will be unblinded.  Those who did not 
receive the vaccine will have the option to receive it in combination with radiation to the 
lesion which is demonstrating disease progression.   
• Participants will be evaluated for objective response, and time to progression of the 
irradiated tumor mass as well as overall survival 
• Up to 55 participants will be accrued to the study 
Randomization Schema 
 
Primary endpoint:  Overall response rate (RECIST 1.1) in the irradiated tumor site(s) 
Secondary endpoints: 
-Progression free survival (irradiated tumor), PFS (other sites), overall survival 
-Patient Report Outcomes 
Exploratory endpoints: 
- 
Evaluations of response rate and PFS using other criteria  
- 
(Volumetric, Growth rate kinetics, Choi)  
- 
To evaluate brachyury-specific T cell response pre-, during, and post-treatment. 
- 
To evaluate other parameters of general immune activation detailed in the protocol. 
- 
To evaluate the quantity and quality of tumor infiltrating lymphocytes and other markers 
of local immune response and inflammation pre- and post-treatment in both groups. 
- 
Daily Activity 
Statistical assumption: 
- Goal: improve ORR from 5% to 30% 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: May 14, 2018 
 
5 
 
Treatment Schema 
 
After C7, study agent doses will be given every 3 months (85 days, -7 / +28 days).  Restaging scans will be 
performed at fixed intervals from the time of completion of radiation: 3 months (-7 / +28 days, corresponds to 
C3D1), 6 months (+/- 4 weeks, corresponds to C6D1), 9 months (+/- 4 weeks, corresponds to C7D1), 12 months (+/- 
4 weeks, corresponds to C8D1), 18 months (+/- 8 weeks, C10D1), 24 months (+/- 8 weeks, C12D1), 36 months (+/- 
8 weeks, C16D1) and yearly thereafter (+/- 8 weeks).  MDASI assessment will take place at baseline and at each 
restaging imaging timepoint. 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: March 27, 2018 
 
59 
 
12.3 APPENDIX C: TREATMENT AND MONITORING SCHEDULE: PRE, DURING AND POST THERAPY 
 
 
Screening 
 
Baseline1 
 
C1 
D1 
 
C1 
D15 
 
C1  
D29 
 
Days 
43-
100 
(+/- 
14) 
 
C2 
D1  
 
C2 
D15 
 
C2 
D2
9 
 
C3 D1 
–  
C5 D1 
C6 D1  
2 years 
 on study  
Post-
treatment 
follow-up 
visit 
History and 
Physical1 
X 
X 
 
 
 
 
 
 
 
 
 
 
Medical 
Assessments2 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X14 
Imaging3 
X3 
 
 
 
 
 
 
 
 
X3 
X3 
 
Urinalysis  
X 
X 
 
X 
X 
 
X 
 
X 
X 
X 
 
Serum HIV 
antibody4 
X 
X 
 
 
 
 
 
 
 
 
 
 
Serum Hepatitis 
B & C5 
X 
 
 
 
 
 
 
 
 
 
 
 
CBC with 
differential, 
platelet count 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X14 
Chemistry6  
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X14 
EKG  
X 
 
 
 
 
 
 
 
X 
 
 
 
Immunology 
(blood)7 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 14 
ANA titer8 
 
X 
 
 
X 
 
 
 
 
 
X 
 
CD3, 4, 8, 19 
subsets, NK 
markers and 
CD4:CD8 
ratio8 
 
X 
 
 
X 
 
 
 
 
 
X 
 
HLA Typing 
X 
 
 
 
 
 
 
 
 
 
 
 
Skin testing9 
X 
 
 
 
 
 
 
 
 
 
 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: March 27, 2018 
 
60 
 
 
 
Screening 
 
Baseline1 
 
C1 
D1 
 
C1 
D15 
 
C1  
D29 
 
Days 
43-
100 
(+/- 
14) 
 
C2 
D1  
 
C2 
D15 
 
C2 
D2
9 
 
C3 D1 
–  
C5 D1 
C6 D1  
2 years 
 on study  
Post-
treatment 
follow-up 
visit 
Serum Beta-
HCG10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Radiotherapy 
 
 
 
 
 
X 
 
 
 
 
 
 
GI-6301 
(Yeast-
Brachyury 
Vaccine) or 
placebo11 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X11 
 
Yeast allergy 
test12 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse 
Events 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
 
Tissue 
Samples13 
 
X 
 
 
 
 
 
 
 
 
X 
 
Concomitant 
Medications 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
 
MDASI 
 
X3 
 
 
 
 
 
 
 
X3 
X3 
 
Actigraphy 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
1 Baseline: H & P and laboratory studies should be completed within 16 days of initiating treatment. Baseline radiographic, ECOG 
performance status, EKG and immunologic studies should be obtained within 28 days of initiating treatment.   
2 Medical assessments:  interim history (since last visit), vital signs, physical examination and ECOG performance status, must be performed within 
3 days of each dose 
3 Radiologic studies consisting of CT chest/abdomen/pelvis and MRI will be performed within 28 days prior to enrollment, after 
completion of cycle 2 (on or around C3 D1, and every 3 months (-7 days / +28 days) thereafter.  After 1 year of SD, PR, or CR, imaging 
may be performed approximately every 6 months during year 2, and then yearly thereafter.  Imaging can be repeated early at the 
discretion of the investigator/physician.  MDASI assessments will take place along with imaging studies. 
4 Serum HIV antibody should be completed within 12 weeks of initiating treatment. A positive screening test must be confirmed by 
detectable virus in the serum by PCR. 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: March 27, 2018 
 
61 
 
5 Serum hepatitis B & C antibody should be completed within 12 weeks of initiating treatment. A positive screening test must be 
confirmed by detectable virus in the serum by PCR. 
6 Chemistry panel:  Na+, K+, Cl-, CO2, glucose, BUN, creatinine, albumin, calcium, magnesium, phosphorus, alkaline phosphatase, ALT, 
AST, total bilirubin, TSH, and LDH. 
7 Blood will be obtained for immunologic assays. Research blood will be drawn at baseline and prior to each dose.  2 SST tubes, 6 green 
top tubes are required. 
8 ANA and CD3, 4, 8, 19 subsets will be drawn at baseline and prior to C6 D1. 
9 For patients with questionable history of yeast allergy, this test is performed at the screening visit to detect if the subject has a 
hypersensitivity to Saccharomyces cerevisiae.  A negative response is required for entry into this trial. 
10 In females of child-bearing age, beta-HCG to be done within 48 hours prior to day 1. 
11 Administered subcutaneously at 4 sites.  Dosing will be given as follows: on C1 D1, C1 D15, C1 D29 (all +/-3 days). Dosing will be 
interrupted for the duration of radiation and will resume 14-28 days post radiation depending on patient schedule and any time required 
to recover.  Treatment is then resumed on C2 D1, C2 D15, C2 D29 (all +/- 3 days).  C3 D1 (28 days (+/- 7 days) after C2 D29) begins 
monthly (28 day +/- 7 days) dosing for 4 doses (cycles 3, 4, 5, and 6).  C6 D1 begins every 3 month (85 days -7/+28 days) dosing, 
which goes on for at least 2 years.  After 2 years on study, doses may be given less frequently (every 6-12 months) based on vaccine 
supply and patient preference 
13 Performed in subjects with a questionable history of allergy to yeast 
13 Baseline tissue sample is preferred.  These may be fresh biopsy samples or archived tissue.  If archived tissue, at least 10 unstained 
slides are required.  On-study biopsy specimens will be analyzed by immunohistochemistry for evidence of immune response within the 
tumor.  These samples may be obtained at 6 or 12 months or at evidence of tumor response or tumor progression.  Biopsy is allowable 
for research purposes at other times at investigator discretion with patient consent to biopsy. 
14Post-treatment follow-up labs are not required if the subject prefers to follow-up via phone contact. 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
NantCell Study number: QUILT-3.011 
CC Protocol #: 15-C-0118  
 
 
 
 
 
OSP#: 1407-1336 
Version Date: July 11, 2018   
 
 
 
 
 
IBC#: RD-15-III-13 
Amendment: I 
NCT Number: NCT02383498 
 
 
 
 
 
 
 
 
 
Title: A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus 
Placebo in Combination with Standard of Care Definitive Radiotherapy in Locally Advanced, 
Unresectable, Chordoma 
 
 
NCI Principal Investigator:  
Mark Gilbert M.D, NOB, CCR, NCI 
 
 
 
 
 
9030 Old Georgetown Road, Bldg. 82, Room 235 A  
 
 
 
 
 
Bethesda, MD 20892 
 
 
 
 
 
Phone: 240-760-6023 
 
 
 
 
 
Email: mark.gilbert@nih.gov  
 
 
Sponsor Contact: 
 
 
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 
 
 
Investigational Agents:  
Drug Name 
GI-6301 Vaccine (Yeast-Brachyury)  
IND Number 
BB-IND # 14895 
Sponsor 
NantCell, Inc. 
Manufacturer/Supplier 
GlobeImmune 
 
Commercial Device: wGT3X-BT manufactured by Actigraph. Associate Investigator in the Diabetes, 
Endocrinology, and Obesity Branch of NIDDK will provide the actigraphy equipment.

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: July 11, 2018 
 
3 
 
PRÉCIS 
Background:  
• Chordoma is a rare disease, affecting about 3,000 people in the United States, with about 
300 new cases diagnosed per year. 
• Brachyury is a member of the T-box family of transcription factors, characterized by a 
highly conserved DNA-binding domain designated as T-domain.   
• Brachyury is expressed universally in chordoma cells. 
• GI-6301 (Yeast-brachyury vaccine) has demonstrated immunogenicity with a tolerable 
and acceptable safety profile in a phase 1 trial. 
• Brachyury specific T cells can lyse human cancer cells expressing brachyury in an MHC 
restricted manner. 
• There have been indications of clinical benefit in patients with chordoma enrolled on the 
phase I trial of GI-6301. 
o 1 Partial Response 
o 1 Mixed Response in Chordoma patients who received Radiation 
o 6 of 9 patients with progressive disease at enrollment had Stable Disease at 
Day 85 restaging 
• In vitro, chordoma cell lines are killed significantly better by brachyury-specific T cells 
after radiation exposure using either proton beam or gamma radiation. 
 
Endpoints: 
Primary Objective:  
• To determine if there is a difference in overall response rate (ORR) defined as complete 
response (CR) or partial response (PR) by RECIST 1.1 in the irradiated tumor site after 
up to 24 months among patients with Chordoma who are treated with radiation plus 
vaccine vs. radiation plus placebo. 
 
Eligibility: 
• Patients at least 18 years old with advanced unresectable, chordoma who are planning to 
be treated with definitive radiotherapy to at least one lesion. 
• No history of autoimmune disease (with exceptions detailed in section 2.1) 
• Measurable disease as defined by RECIST 1.1 
• Adequate organ function 
 
Design: 
• Randomized, double-blind, placebo controlled phase 2 clinical trial of radiation plus 
placebo vs. radiation plus yeast-brachyury vaccine in patients with chordoma. 
• Participants will be randomized on a 1:1 basis to the two arms 
• Participants assigned to the placebo arm will be allowed to cross-over at time of 
confirmed disease progression. 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
Version Date: July 11, 2018 
 
4 
 
• Participants who have had a response in the irradiated target lesion and then have 
progression outside of the irradiated site will have the option to receive irradiation or 
other local intervention to the area of disease outside of the radiation field. Progression 
will be determined only by the target lesion which had been irradiated. Other lesions will 
be monitored and intervened upon as clinically necessary. If alternative systemic therapy 
is required, patients would be taken off study at that point. 
• Radiographic progression at the irradiated lesion will be unblinded.  Those who did not 
receive the vaccine will have the option to receive it in combination with radiation to the 
lesion which is demonstrating disease progression.   
• Participants will be evaluated for objective response, and time to progression of the 
irradiated tumor mass as well as overall survival 
• Up to 55 participants will be accrued to the study 
Randomization Schema 
 
Primary endpoint:  Overall response rate (RECIST 1.1) in the irradiated tumor site(s) 
Secondary endpoints: 
-Progression free survival (irradiated tumor), PFS (other sites), overall survival 
-Patient Report Outcomes 
Exploratory endpoints: 
- 
Evaluations of response rate and PFS using other criteria  
- 
(Volumetric, Growth rate kinetics, Choi)  
- 
To evaluate brachyury-specific T cell response pre-, during, and post-treatment. 
- 
To evaluate other parameters of general immune activation detailed in the protocol. 
- 
To evaluate the quantity and quality of tumor infiltrating lymphocytes and other markers 
of local immune response and inflammation pre- and post-treatment in both groups. 
- 
Daily Activity 
Statistical assumption: 
- Goal: improve ORR from 5% to 30% 
 

Abbreviated Title: Ph 2 Yeast-Brachyury Chordoma 
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early at the discretion of the investigator/physician.  MDASI assessments will take place along 
with imaging studies. 
4 Serum HIV antibody should be completed within 12 weeks of initiating treatment. A positive 
screening test must be confirmed by detectable virus in the serum by PCR. 
5 Serum hepatitis B & C antibody should be completed within 12 weeks of initiating treatment. A 
positive screening test must be confirmed by detectable virus in the serum by PCR. 
6 Chemistry panel:  Na+, K+, Cl-, CO2, glucose, BUN, creatinine, albumin, calcium, magnesium, 
phosphorus, alkaline phosphatase, ALT, AST, total bilirubin, TSH, and LDH. 
7 Blood will be obtained for immunologic assays. Research blood will be drawn at baseline and prior 
to each dose.  2 SST tubes, 6 green top tubes are required. 
8 ANA and CD3, 4, 8, 19 subsets will be drawn at baseline and prior to C6 D1. 
9 For patients with questionable history of yeast allergy, this test is performed at the screening visit 
to detect if the subject has a hypersensitivity to Saccharomyces cerevisiae.  A negative response is 
required for entry into this trial. 
10 In females of child-bearing age, beta-HCG to be done within 48 hours prior to day 1. 
11 Administered subcutaneously at 4 sites.  Dosing will be given as follows: on C1 D1, C1 D15, C1 
D29 (all +/-3 days). Dosing will be interrupted for the duration of radiation and will resume 14-28 
days post radiation depending on patient schedule and any time required to recover.  Treatment is 
then resumed on C2 D1, C2 D15, C2 D29 (all +/- 3 days).  C3 D1 (28 days (+/- 7 days) after C2 
D29) begins monthly (28 day +/- 7 days) dosing for 4 doses (cycles 3, 4, 5, and 6).  C6 D1 begins 
every 3 month (85 days -7/+28 days) dosing, which goes on for at least 2 years.  After 2 years on 
study, doses may be given less frequently (every 6-12 months) based on vaccine supply and patient 
preference 
13 Performed in subjects with a questionable history of allergy to yeast 
13 Baseline tissue sample is preferred.  These may be fresh biopsy samples or archived tissue.  If 
archived tissue, at least 10 unstained slides are required.  On-study biopsy specimens will be 
analyzed by immunohistochemistry for evidence of immune response within the tumor.  These 
samples may be obtained at 6 or 12 months or at evidence of tumor response or tumor progression.  
Biopsy is allowable for research purposes at other times at investigator discretion with patient 
consent to biopsy. 
14Post-treatment follow-up labs are not required if the subject prefers to follow-up via phone contact.  
 
 
12.4 APPENDIX D: MODIFIED CHOI CRITERIA 
The Choi Criteria was introduced for radiographic evaluation of gastrointestinal stromal tumors 
treated with imatinib mesylate44,45 and has been evaluated in other soft tissue sarcomas 43 and 
renal cell carcinoma46.   
 
The differences between RECIST and Choi Criteria are defined in the table below: