A Phase 2 Study of GI-6207 in Patients With Recurrent Medullary Thyroid Cancer
Phase: PHASE2
Conditions: Medullary Thyroid Cancer (MTC)
Sponsor: NantCell, Inc.

Abbreviated title:  GI-6207 in MTC 
Version Date: May 14, 2018 
 
8 
STATISTICAL CONSIDERATIONS 
The primary objective of this study is to assess whether use of GI-6207 is able to result in 
reductions of the growth rates of tumors in patients with MTC. The changes in growth rates will 
be compared between two arms with either initial assignment to vaccine or surveillance, as well 
as secondarily determining if there is a significant change within the arm that initially receives 
surveillance followed by 6 months of vaccine. 
Prior to randomization, patients will be stratified according to whether they were noted to have a 
calcitonin doubling time of <24 months vs. >24 months at baseline. 
The primary endpoint will be the change from baseline to 6 months of the growth rate parameter.  
With 17 total patients per arm (34 total), with complete measurements of this main parameter at 
baseline and at 6 months after randomization, there would be 80% power to detect a difference 
between the two groups with respect to a change from baseline to 6 months equal to 1.0 standard 
deviations of the change (1.0 effect size) using a two-tailed 0.05 level two-sample t-test. In 
practice, if the differences from baseline to 6 months are not normally distributed on both arms 
(that is, if p<0.05 by a Shapiro Wilks test) then a Wilcoxon rank sum test will be performed 
instead. 
As an important secondary objective, using the surveillance arm, two related secondary 
endpoints will be explored, both the actual magnitude of the change in the growth rate parameter 
as well as the fraction who exhibit a substantial, 50% decline in the growth rate as a result of 
treatment. 
For the 17 patients will be enrolled on the surveillance arm, the growth rate determined at 
12 months (after 6 months of vaccine) will be subtracted from that obtained at 6 months (after 
surveillance) to determine the actual change in the growth rate for receiving vaccine after 
6 months of surveillance. With 17 patients, there is 82% power to detect a difference in the 
values at the two time points equal to ¾ of the SD of the change (.75 effect size) assuming that a 
two-tailed 0.05 alpha level paired t-test is used. 
Also, as an additional secondary exploration, using all 17 patients on the surveillance arm, the 
fraction that experiences a 50% decline relative to the time of starting vaccine will be 
determined. Using an exact binomial test, 17 patients will have 83% power to test whether the 
fraction exceeds a null fraction of 20% and is consistent with 50% who have 50% declines, with 
a one-tailed 0.05 alpha level test. In practice, the fraction with a 50% decline will have a 95% 
confidence interval created about the result in order to describe what values it would be 
consistent with. 
Exploratory analyses will also be performed to compare the growth rate changes at additional 
time points, such as 7, 10 and 12 months. 
It is expected that the trial will accrue approximately 1-2 patients per month may be accrued; 
thus it is expected that this study may enroll 34 evaluable patients within 24-30 months. To allow 
for the possibility of a rare inevaluable patient, the accrual ceiling will be set at 37. 
 
Confidential and Proprietary 
47 

 
Abbreviated Title: GI-6207 in MTC 
NantCell Study Number: QUILT-3.006 
 
 
NCI Protocol #: 13-C-0095  
 
 
 
 
 
OSP#: 1301-1199 
Version Date: May 14, 2018  
 
 
 
 
 
IBC#: RD-13-I-10 
Amendment: G 
 
 
Title: A phase 2 study of GI-6207 in patients with recurrent medullary thyroid cancer 
 
 
NCI Principal Investigator: 
 
Ravi A. Madan, M.D. 
Genitourinary Malignancies Branch, CCR, NCI 
10 Center Drive 
 
 
 
 
Building 10, Room 13N240  
Bethesda, MD 20892 
Phone: 301-480-7168 
Email: madanr@mail.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 Agent: 
 
 
 
 
 
 
 
 
 
Drug Name:  
  
 
GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)] 
IND Number:  
  
 
15344 
Sponsor: 
      
 
NantCell, Inc.  
Manufacturer/Supplier: 
GlobeImmune 
Confidential and Proprietary 
1 

Abbreviated title:  GI-6207 in MTC 
Version Date: May 14, 2018 
 
Schema 
 
 
 
 Randomize 
Vaccine (n=17) 
Vaccine  
Surveillance (n=17) 
• 
All patients enrolled will have evaluable disease 
• 
Consistent with phase 1 study dosing, all patients will be given GI-6207 
every 2 weeks for 3 months and then monthly.  Dose = 40/YU. 
• 
Half of the patients will be on surveillance for 6 months to determine a 
growth rate for comparison to those who start GI-6207 immediately  
• 
The primary endpoint will compare the calcitonin growth rate in the 
GI-6207 arm at 6 months, with patients on the surveillance arm at 
6 months. 
• 
A secondary endpoint will compare the surveillance arm growth rate 
after 6 months of GI-6207 to each patient’s own baseline growth rate 
determined after 6 months of surveillance. 
• 
 Patients will be evaluated with radiographic imaging at enrollment and 
every 3 months while on study 
• 
Patients will be removed from treatment if there is clinical progression 
or radiographic progression (based on the immune-related response 
criteria) while on GI-6207 treatment 
• 
Patients will be stratified based on pre-treatment doubling time of less 
than or greater than 24 months. 
• 
Once patients have completed one year of therapy with GI-6207, patients 
without radiographic progression will have the option to receive vaccine 
every 3 months for an additional 12 months.  Patients who remain on 
vaccine will continue to be scanned every 3 months. 
6 months 
Confidential and Proprietary 
2 

Abbreviated title:  GI-6207 in MTC 
Version Date: May 14, 2018 
 
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: ______________
Confidential and Proprietary 
3 

 
PRÉCIS 
Background: 
• CEA is overexpressed in multiple malignancies, including medullary thyroid cancer where 
CEA is universally expressed on tumor cells. 
• There is no standard treatment for patients with asymptomatic or minimally symptomatic, 
metastatic medullary thyroid cancer. The only effective FDA-approved therapy (vandetanib) 
comes with significant toxicity, so it is not used until patients have symptomatic or rapidly 
progressing disease. 
• Preclinical studies have shown that GI-6207 can induce a strong immune response to CEA as 
well as therapeutic anti-tumor responses.  
• A previous phase 1 GI-6207 study has demonstrated safety and enhanced immune response 
in some patients. 
• Preliminary data suggests that tumor growth rates can be calculated in medullary thyroid 
cancer patients within 3 months. 
• Retrospective data from prostate cancer studies suggest that vaccines can alter tumor growth 
rates within 3-4 months. 
 
Objective: 
Primary 
• To determine the effect of GI-6207 on calcitonin growth rate kinetics after 6 months of 
therapy in patients with medullary thyroid cancer. 
 
Eligibility: 
• Patients will have evidence of metastatic medullary thyroid cancer including disease that is 
evaluable on bone or CT scan.  
• Patients with minimal or no disease related-symptoms (minimal symptoms will include those 
that do not affect activities of daily living or pain that does not require regularly schedule 
narcotics). 
• ECOG 0-1 
• No previous chemotherapy 
• No previous vandetanib 
• Should have no autoimmune diseases; no evidence of being immunocompromised; no 
serious inter-current medical illness; no cardiac disease; no prior splenectomy. (History of 
previous thyroid autoimmune disease will be allowed as these patients will have had total 
thyroidectomy.) 
• No brain metastasis, history of seizures, encephalitis, or multiple sclerosis 
• No pericardial-based masses greater than 1 cm or thoracic lesions larger than 2 cm 
 
Confidential and Proprietary 
4 

Abbreviated title:  GI-6207 in MTC 
Version Date: May 14, 2018 
 
Design: 
• Randomized, phase 2 study to determine the effect of GI-6207 on calcitonin growth rate after 
6 months of GI-6207 
• Patients will be randomized to either initial GI-6207 therapy or 6 months of surveillance 
followed by GI-6207 therapy.   
• GI-6207 will be administered subcutaneously at 4 sites at dose of 10 yeast units per site, 
biweekly for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly up to 1 year of treatment.  
(For patients randomized to surveillance and then GI-6207, they will get a full year of GI-
6207 after a 6 month surveillance period.) 
• Once patients have completed one year of therapy with GI-6207, patients without 
radiographic progression will have the option to receive vaccine every 3 months for an 
additional 12 months.  Patients who remain on vaccine will continue to be scanned every 3 
months. 
• Immune monitoring via apheresis will be done prior to enrollment and at 6 months for all 
appropriate and consenting patients. Patients who are evaluable for immunologic response by 
the ELISPOT Assay (HLA 02, 03 and 24) will have apheresis at start of GI-6207 therapy and 
then every 3 months while on GI-6207 treatment when feasible.   
 
Confidential and Proprietary 
5 

Abbreviated title: GJ-6207 in MTC 
Version Date: lvfay 14, 2018 
SPONSOR SIGNATURE 
Study Title: 
A phase 2 study of GI-6207 in patients with recurrent medullary 
thyroid cancer 
Study Number: 
QUILT-3.006 
Version Date: 
14 May2018 
This clinical trial protocol was subject to critical review and has been approved by NantCell. 
The following personnel contribu _ed to writing and/or approving this protocol: 
Signed: 
Date: 
. Lee, MD 
enior 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 
75 

 
Confidential and Proprietary 
1 
Abbreviated Title: GI-6207 in MTC 
Study number: QUILT-3.006 
 
 
NCI Protocol #: 13-C-0095  
 
 
 
 
 
OSP#: 1301-1199 
Version Date: 30 01 2018 
 
 
 
 
 
 
IBC#: RD-13-I-10 
Amendment: F 
 
 
Title: A Phase 2 study of GI-6207 in patients with recurrent medullary thyroid cancer 
 
 
NCI Principal Investigator: 
 
Ravi A. Madan, M.D. A, B, C, D, E, F 
Genitourinary Malignancies Branch, CCR, NCI 
10 Center Drive 
 
 
 
 
Building 10, Room 13N240  
Bethesda, MD 20892 
Phone: 301-480-7168 
Email: madanr@mail.nih.gov 
 
Statistician: 
 
 
 
*Seth Steinberg, Ph.D., OCD, CCR, NCI E, F 
 
NIH Associate Investigators:  
 
 
 
 
 
 
 
 
 
 
Non-NIH Associate Investigator: 
James L. Gulley, M.D., Ph.D., GMB, CCR, NCI A, B, C, D, E, F  
Julius Strauss, M.D., OCD, CCR, NCI A, B, C, D, E, F  
Marijo Bilusic, M.D., Ph.D., GMB, CCR, NCI A, B, C, D, E, F 
Jaydira Del Rivero, M.D., OCD, CCR, NCI A, B, C, D, E, F 
Myrna Rauckhorst, R.N., OCD, CCR, NCI A, B, C, E, F  
Sheri McMahon, R.N., OCD, CCR, NCI A, B, C, E, F  
Guinevere Chun, R.N., OCD, CCR, NCI A, B, C, E, F  
Amy Hankin, P.A., GMB, CCR, NCI A, B, C, D, E, F  
Lisa Cordes, PharmD, Pharmacy Department, CC E, F 
 
Philip M. Arlen, M.D. [V], GMB, CCR, NCI A, B, E, F 
 
Referral Contact/ 
Study Coordinator: 
 
Myrna Rauckhorst, R.N., OCD, CCR, NCI 
10 Center Drive 
Building 10, Room 13N210 
Bethesda, MD 20892 
Phone: 240-760-6069 
Email: mrauckhorst@mail.nih.gov 
 

Abbreviated title:  GI-6207 in MTC 
Version Date:  30 01 2018 
 
Confidential and Proprietary 
2 
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 
 
 
*Indicates Associate Investigators who will not be making protocol-related medical decisions. 
 
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 Agent: 
 
 
 
 
 
 
 
 
Drug Name:  
  
 
GI-6207 [Recombinant Saccharomyces cerevisiae-CEA (610D)] 
IND Number:  
  
 
15344 
Sponsor: 
      
 
NantCell, Inc.  
Manufacturer/Supplier: 
GlobeImmune 

Abbreviated title:  GI-6207 in MTC 
Version Date:  30 01 2018 
 
Confidential and Proprietary 
3 
Schema 
 
 
 
 
 
 Randomize 
Vaccine (n=17) 
Vaccine  
Surveillance (n=17) 
• 
All patients enrolled will have evaluable disease 
• 
Consistent with phase I study dosing, all patients will be given GI-6207 
every 2 weeks for 3 months and then monthly.  Dose = 40/YU. 
• 
Half of the patients will be on surveillance for 6 months to determine a 
growth rate for comparison to those who start GI-6207 immediately  
• 
The primary endpoint will compare the calcitonin growth rate in the 
GI-6207 arm at 6 months, with patients on the surveillance arm at 
6 months. 
• 
A secondary endpoint will compare the surveillance arm growth rate 
after 6 months of GI-6207 to each patient’s own baseline growth rate 
determined after 6 months of surveillance. 
• 
 Patients will be evaluated with radiographic imaging at enrollment and 
every 3 months while on study 
• 
Patients will be removed from treatment if there is clinical progression 
or radiographic progression (based on the immune-related response 
criteria) while on GI-6207 treatment 
• 
Patients will be stratified based on pre-treatment doubling time of less 
than or greater than 24 months. 
• 
Once patients have completed one year of therapy with GI-6207, patients 
without radiographic progression will have the option to receive vaccine 
every 3 months for an additional 12 months.  Patients who remain on 
vaccine will continue to be scanned every 3 months. 
 
 
6 months 

Abbreviated title:  GI-6207 in MTC 
Version Date:  30 01 2018 
 
Confidential and Proprietary 
4 
PRÉCIS 
Background: 
• CEA is overexpressed in multiple malignancies, including medullary thyroid cancer where 
CEA is universally expressed on tumor cells. 
• There is no standard treatment for patients with asymptomatic or minimally symptomatic, 
metastatic medullary thyroid cancer. The only effective FDA-approved therapy (vandetanib) 
comes with significant toxicity, so it is not used until patients have symptomatic or rapidly 
progressing disease. 
• Preclinical studies have shown that GI-6207 can induce a strong immune response to CEA as 
well as therapeutic anti-tumor responses.  
• A previous Phase I GI-6207 study has demonstrated safety and enhanced immune response 
in some patients. 
• Preliminary data suggests that tumor growth rates can be calculated in medullary thyroid 
cancer patients within 3 months. 
• Retrospective data from prostate cancer studies suggest that vaccines can alter tumor growth 
rates within 3-4 months. 
 
Objective: 
Primary 
• To determine the effect of GI-6207 on calcitonin growth rate kinetics after 6 months of 
therapy in patients with medullary thyroid cancer. 
 
Eligibility: 
• Patients will have evidence of metastatic medullary thyroid cancer including disease that is 
evaluable on bone or CT scan.  
• Patients with minimal or no disease related-symptoms (minimal symptoms will include those 
that do not affect activities of daily living or pain that does not require regularly schedule 
narcotics.) 
• ECOG 0-1 
• No previous chemotherapy 
• No previous vandetanib 
• Should have no autoimmune diseases; no evidence of being immunocompromised; no 
serious inter-current medical illness; no cardiac disease; no prior splenectomy. (History of 
previous thyroid autoimmune disease will be allowed as these patients will have had total 
thyroidectomy.) 
• No brain metastasis, history of seizures, encephalitis, or multiple sclerosis 
• No pericardial-based masses greater than 1 cm or thoracic lesions larger than 2 cm 
 

Abbreviated title:  GI-6207 in MTC 
Version Date:  30 01 2018 
 
Confidential and Proprietary 
5 
Design: 
• Randomized, phase 2 study to determine the effect of GI-6207 on calcitonin growth rate after 
6 months of GI-6207 
• Patients will be randomized to either initial GI-6207 therapy or 6 months of surveillance 
followed by GI-6207 therapy.   
• GI-6207 will be administered subcutaneously at 4 sites at dose of 10 yeast units per site, 
biweekly for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly up to 1 year of treatment.  
(For patients randomized to surveillance and then GI-6207, they will get a full year of GI-
6207 after a 6 month surveillance period.) 
• Once patients have completed one year of therapy with GI-6207, patients without 
radiographic progression will have the option to receive vaccine every 3 months for an 
additional 12 months.  Patients who remain on vaccine will continue to be scanned every 3 
months. 
• Immune monitoring via apheresis will be done prior to enrollment and at 6 months for all 
appropriate and consenting patients. Patients who are evaluable for immunologic response by 
the ELISPOT Assay (HLA 02, 03 and 24) will have apheresis at start of GI-6207 therapy and 
then every 3 months while on GI-6207 treatment when feasible.