A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas
Phase: PHASE1
Conditions: Metastatic Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer
Sponsor: NewLink Genetics Corporation

 
 
 
 
 
 
 
Clinical Trial Protocol 
NLG-2104 
 
A Phase 1/2 Study of Indoximod in Combination with Gemcitabine and Nab-
Paclitaxel in Patients with Metastatic Adenocarcinoma of the Pancreas 
 
 
IND #: 
 
Clinicaltrials.gov #: NCT02077881 
 
Version 4 Dated:  07/25/2016 
Replaces Version 3 Dated: 06/05/2014 
 
 
 
Study Sponsor: 
NewLink Genetics Corporation 
Iowa State University Research Park 
2503 South Loop Drive, Suite 5100 
Ames, Iowa, USA  50010 
 
 
 
Investigational Agent: 
Indoximod (1-methyl-D-tryptophan, D-1MT) 
 
 
 
 
STATEMENT OF CONFIDENTIALITY 
The confidential information in the following document is provided to you as an investigator, potential 
investigator, or consultant, for review by you, your staff, and applicable institutional review board(s).  It is 
understood that the information will not be used, divulged, or published without the written consent of 
NewLink Genetics Corporation, except to the extent necessary to obtain informed consent from those persons 
to whom study medication may be administered. 

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Lead Institution: 
University of Pittsburgh Cancer Institute 
 
 
 
 
Investigators: 
 
 
Nathan Bahary, MD, PhD. 
  
Associate Professor of Medicine 
 
5117 Centre Ave. 
 
University of Pittsburgh Cancer Institute,  
 
Pittsburgh, Pennsylvania 15213, USA 
 
 
Herbert J. Zeh, III, MD 
 
Associate Professor of Surgery 
 
Suite 417 UPMC Cancer Pavilion 
 
5150 Center Ave 
 
Pittsburgh, PA 15101 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS: 
 
Title: 
A Phase 1/2 Study of Indoximod in Combination with Gemcitabine and 
Nab-Paclitaxel in Patients with Metastatic Adenocarcinoma of the 
Pancreas 
 
Primary Objective: 
Phase 1 component: To characterize the regimen limiting toxicity (RLT) 
and determine a recommended phase 2 dose of indoximod when 
administered with a standard of care chemotherapy backbone consisting of 
gemcitabine plus nab-paclitaxel. 
 
 
Phase 2 component: To evaluate efficacy as determined by overall 
survival (OS) in patients with metastatic adenocarcinoma of the pancreas. 
 
 
Secondary Objectives: 
 
a) To examine biomarker responses of gemcitabine and nab-
paclitaxel with indoximod. 
b) To determine the response rate of the combination indoximod with 
gemcitabine plus nab-paclitaxel. 
c) To determine the time to progression and progression-free survival 
with the combination indoximod with gemcitabine plus nab-
paclitaxel. 
 
 
Population: 
Patients with metastatic pancreas cancer who have NOT received any 
prior chemotherapy agents in the metastatic setting. 
 
Sample Size: 
Up to 98 patients will be initially enrolled in this study (up to 18 in phase 
1, and 80 patients in phase 2).  
 
 
An additional Phase 2 expansion cohort of up to 40 patients will be added 
for the purpose of obtaining matched pre-treatment and on-treatment 
tumor biopsies. 
 
Investigational Drug: Indoximod consists of an inhibitor of the immunoregulatory enzyme, 
indoleamine 2,3-dioxygenase.  Indoximod is a sterile powder mixed with 
inert ingredients and packaged as 200 mg capsules. 
 
 

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Dosage Escalation: 
Phase 1 component: Patients will be assigned in cohorts of three. Dose 
escalation will occur according to a standard 3 x 3 dose escalation design 
in 28 day cycles. 
 
 
 
Safety Analysis: 
To establish the safety and the recommended phase 2 dose of indoximod 
in combination with gemcitabine plus nab-paclitaxel, it is necessary to 
determine the attribution of all toxicities. However, the standard of care 
backbone chemotherapy is associated with significant toxicities that may 
confound efforts to define the true toxicity of indoximod when added to 
this backbone.  The high rate of toxicity of the backbone regimen may 
result in an inaccurate rejection of all dose levels of any new agents when 
added. It has been recommended in these situations that a “pragmatic” 
approach be adopted for determining dose-limiting toxicities.  In this 
approach, only grade 3 and 4 toxicities that are attributable to the test 
agent and result in the delay of the administration of the backbone 
chemotherapy, gemcitabine plus nab-paclitaxel, will be considered as 
regimen limiting. Additionally, any toxicities not before seen with either 
the backbone chemotherapy alone or with indoximod alone will be 
considered regimen associated toxicities and not ascribed to either agent in 
isolation. 
 
Duration of Treatment: Patients may continue on treatment until they experience progressive 
disease or unacceptable toxicity, require palliative radiotherapy, 
withdraw consent, or their physician feels it is no longer in their best 
interest to continue on treatment. 
 
 
 
 
Dose Level Indoximod DOSE (oral)
Nab-paclitaxel (IV) 
Gemcitabine (IV) 
1 
600 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000 mg/m2  weekly x 3 
2 
1000 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000 mg/m2  weekly x 3 
3 
1200 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000 mg/m2  weekly x 3 

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TREATMENT SCHEMATIC  
Phase 1 and Phase 2 
 
Study Day -30 to –0 
Patients prescreened for protocol eligibility 
 
Cycle 1 Day 1 
Indoximod (dose dictated by escalation level) po daily starts and continues throughout study 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
 
Cycle 1 Day 8 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
Indoximod po continues 
 
Cycle 1 Day 15 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
Indoximod po continues 
 
Cycle 1 Day 22 
Rest from Chemotherapy 
Indoximod (dose dictated by escalation level) po daily continues 
 
Cycle 2 Day 1 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
Indoximod po continues 
 
Cycle 2 Day 8 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
Indoximod po continues 
 
Cycle 2 Day 15 
Nab-paclitaxel 125 mg/m2 given intravenously over 30 to 40 minutes followed by 
Gemcitabine 1000 mg/m2 intravenously over 30 to 40 minutes 
Indoximod po continues 
 
Cycle 2 Day 22 
Rest from Chemotherapy 
Indoximod (dose dictated by escalation level) po daily continues 
Evaluate for Response (imaging and biomarkers) 
 
Treatment may continue until disease progression or significant toxicity 

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Table of Contents 
1.0 
OBJECTIVES ..................................................................................................................10 
1.1 
Primary objectives .................................................................................................10 
1.2 
Secondary objectives .............................................................................................10 
2.0 
BACKGROUND ..............................................................................................................10 
2.1 
Adenocarcinoma of the exocrine pancreas ............................................................10 
2.2 
Immune suppression, pancreatic cancer and Indolamine 2,3 dioxygenase 
(IDO) ......................................................................................................................11 
2.3 
Indoximod (1-methyl-D-tryptophan, NSC-
; IND#
, IND#
, 
IND#
) .........................................................................................................11 
2.4 
Gemcitabine ...........................................................................................................12 
2.5 
FOLFIRINOX ........................................................................................................13 
2.6 
Paclitaxel Albumin-bound Particles (Nab-Paclitaxel) ...........................................13 
2.7 
Rationale for current study .....................................................................................14 
2.8 
Rationale for Phase 1 design ..................................................................................14 
3.0 
STUDY POPULATION ..................................................................................................15 
3.1 
Inclusion Criteria: ..................................................................................................15 
3.2 
Exclusion Criteria: .................................................................................................17 
3.3 
Inclusion of Women and Minorities ......................................................................18 
3.4 
On Study Tests .......................................................................................................18 
3.4.1 
Baseline Assessment .............................................................................18 
3.4.2 
Additional On-Study Tests ....................................................................18 
4.0 
STUDY DESIGN AND METHODS...............................................................................19 
4.1 
Study Design ..........................................................................................................19 
4.2 
Phase 1 treatment plan ...........................................................................................20 
4.2.1 
Definition of Regimen-Limiting Toxicity (RLT) .................................20 
4.2.2 
Dose Escalation Rules ...........................................................................21 
4.3 
Phase 2 Treatment Plan ..........................................................................................22 
4.4 
Follow-up Phase.....................................................................................................23 
5.0 
REGISTRATION PROCEDURES ................................................................................23 
5.1 
Registration Process ...............................................................................................23 
6.0 
STUDY MEDICATIONS AND PROCEDURES ..........................................................24 
6.1 
Study Agent Administration ..................................................................................24 
6.2 
Indoximod Administration .....................................................................................24 
6.3 
Gemcitabine Plus Nab-Paclitaxel Administration .................................................24 
6.3.1 
Premedication ........................................................................................24 
6.3.2 
Treatment and Dosing ...........................................................................24 

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14.2.1 
Evaluation of Target Lesions ................................................................51 
14.2.2 
Evaluation of Non-Target Lesions ........................................................51 
14.2.3 
Evaluation of Best Overall Response ....................................................52 
14.2.4 
Duration of Response ............................................................................53 
14.3 
Overall Survival .....................................................................................................53 
14.4 
Progression-Free Survival ......................................................................................53 
14.5 
Immune-related Response Criteria ........................................................................53 
14.5.1 
Antitumor response based on total measurable tumor burden ..............54 
14.5.2 
Time-point response assessment using irRC.........................................54 
14.5.3 
Overall response using the irRC ...........................................................54 
15.0 
DATA REPORTING / REGULATORY REQUIREMENTS .....................................54 
15.1 
Regulatory Compliance/Good Clinical Practices ..................................................55 
15.2 
Administrative Requirements ................................................................................56 
15.3 
Human Subjects Protection ....................................................................................58 
16.0 
STATISTICAL METHODS ...........................................................................................59 
16.1.1  General Considerations ..........................................................................................59 
16.1.2 
Determination of Sample Size ..............................................................59 
16.2 
Analysis Populations ..............................................................................................60 
16.3 
Primary and Secondary Endpoints .........................................................................61 
16.3.1 
Phase 1 Component Primary Endpoints ................................................61 
16.3.2 
Phase 2 Component Primary Efficacy Endpoint ...................................61 
16.3.3 
Phase 2 Component Secondary Endpoints ............................................61 
16.4 
Safety Analysis ......................................................................................................62 
17.0 
REFERENCES .................................................................................................................63 
18.0 
APPENDICES ..................................................................................................................64 
18.1 
Appendix A: Performance Status Criteria .............................................................64 
18.2 
Appendix B. Study Medication Diary ...................................................................65 
18.3 
Appendix C: Informed Consent Form Template ...................................................66 
 
 
 

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RESEARCH PROTOCOL ABSTRACT 
 
This is a phase 1/2 trial designed to efficiently identify the regimen limiting toxicity (RLT) and 
recommended phase 2 dose (RP2D) for the combination of the immunotherapeutic agent 
indoximod when administered in combination with standard of care chemotherapy gemcitabine 
plus nab-paclitaxel in patients with metastatic adenocarcinoma of the pancreas. All patients will 
receive the same standard gemcitabine plus nab-paclitaxel regimen, plus indoximod in doses 
increasing from 600 mg twice daily to, potentially, 1200 mg twice daily. Doses of indoximod 
will be allocated using a standard three plus three dose escalation.  RLT will be considered as 
only grade 3 and 4 toxicities that are attributable to the test agent and result in the delay of the 
administration of the backbone chemotherapy, gemcitabine plus nab-paclitaxel.  Every 2 cycles 
(8 weeks), patients will have repeat imaging to assess response. Corollary biomarkers will be 
assessed at the same time points. 
 
1.0 
OBJECTIVES 
1.1 
  Primary objectives 
Phase 1 component: To characterize the regimen limiting toxicity and recommended phase 2 
dose of indoximod when administered with gemcitabine plus nab-paclitaxel. 
 
Phase 2 component: To evaluate efficacy as determined by overall survival (OS) in patients with 
metastatic adenocarcinoma of the pancreas. 
 
1.2 
  Secondary objectives 
a) To examine biomarker responses of gemcitabine and nab-paclitaxel with indoximod. 
b) To determine the response rate of the combination indoximod with gemcitabine plus nab-
paclitaxel. 
c) To determine the time to progression and progression-free survival with the combination 
indoximod with gemcitabine plus nab-paclitaxel. 
2.0 
BACKGROUND 
2.1 
 Adenocarcinoma of the exocrine pancreas  
Pancreatic cancer is a major unsolved public health problem in the United States, with 
approximately 44,000 new cases in the year 2012, making it the tenth most common malignancy 
in adult men and ninth in women.  It ranks as the fourth leading cause of cancer deaths, 
accounting for 7 % of all cancer-related deaths in the United States.   Five-year survival is less 
than 5% for all stages.  Currently, the only potentially curative therapy is surgical resection. 
Nonetheless, many patients who undergo surgical resection derive limited therapeutic benefit. 
Survival of patients who undergo surgical resection followed by adjuvant radio-chemotherapy 
for localized non-metastatic adenocarcinoma of the pancreas is at best 15% at 5 years, and the 

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continue the development of this drug with the Drug Development Group (DDG) at NCI.  
Extramural resources were committed to perform the IND-directed preclinical work.  They were 
able to demonstrate good oral bioavailability with favorable pharmacokinetics with once daily 
dosing.  Furthermore, no significant toxicity was observed in animals. 
 
The phase 1 trials of indoximod (IND#
 and #
) enrolled 65 patients with a variety of 
solid malignancies (breast, colon, melanoma, sarcoma, pancreatic, lung).  The highest dose of 
indoximod administered was 2000 mg PO twice daily given in continuous 28 day cycles.  
Because no dose-limiting toxicity was reached, a maximally tolerated dose of the agent was not 
identified.  The agent was well tolerated and good oral bioavailability was demonstrated. Five 
patients demonstrated prolonged stabilization of disease greater than six months, and there were 
instances of mixed responses observed.  There were no confirmed objective responses. 
 
Objective responses have been seen in a phase 1b study (Protocol 8784 under IND78060) 
investigating indoximod given with docetaxel for metastatic solid tumors. Twenty-seven subjects 
were enrolled onto this study with 22 subjects being evaluable for response.  Docetaxel was 
administered at 60 mg/m2 intravenously every 3 weeks dose levels 1-4 and 75 mg/m2 for dose 
level 5. Indoximod was given at 300, 600, 1000, 2000, and 1200 mg PO twice daily continuously 
for levels 1-5, respectively.  Four patients (2 breast, 1 NSCLC, 1 thymic tumor) achieved a 
partial response (18%), one patient achieved stable disease for longer than 6 months (4%), nine 
patients achieved stable disease for less than 6 months (36%), and eight patients had progressive 
disease (36%). No drug-drug interactions were noted. (Soliman, HH et al. 2014).  
 
 
2.4 
Gemcitabine  
Gemcitabine chemotherapy is the standard of care for inoperable pancreatic cancer, although its 
clinical activity is modest.  In the initial phase 2 trial of single-agent gemcitabine, an 11% partial 
response rate was observed (Casper, Green et al. 1994).  A phase 3 randomized study of 
gemcitabine versus 5-flourouracil in 126 patients reported a 5% objective response rate in the 
gemcitabine arm, with a median survival of 5.65 months and a 1-year survival rate of 18% 
(Burris, Moore et al. 1997). Twenty-four percent of patients in the gemcitabine arm experienced 
a clinical benefit, consisting of improved pain control, performance status, or weight 
stabilization.  In 1996, the US Food and Drug Administration (FDA) approved gemcitabine for 
the treatment of locally advanced and metastatic pancreatic cancer.   
 
Despite numerous trials of novel agents given alone or in combination with gemcitabine, little 
has improved upon these very modest results. It was not until the 2005 National Cancer Institute 
of Canada report of a phase 3 trial of gemcitabine plus erlotinib versus gemcitabine that any 
combination was shown to be superior to gemcitabine monotherapy. Although statistically 
significant (hazard ratio 0.82), the absolute improvement in survival, (5.91 months with 
gemcitabine, 6.24 months with the combination) was once again, exceedingly modest (Moore, 
Goldstein et al. 2007) and no difference in response rates was seen in the combination arm as 
compared to gemcitabine alone.  As such, although this combination is a licensed indication for 
pancreatic cancer, gemcitabine plus erlotinib is not a widely accepted standard of care. 
 

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2.5 
FOLFIRINOX 
In the metastatic setting, FOLFIRINOX was compared to standard gemcitabine monotherapy in 
342 patients with an ECOG PS0 or 1. The primary endpoint was (OS), with a median OS of 11.1 
months in the FOLFIRINOX group vs. 6.8 months in the gemcitabine group (HR for death, 0.57; 
95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival (PFS) 
was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (HR for 
disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective RR was 31.6% in the 
FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001) (Conroy et al. 2011). The 
toxicities of FOLFIRINOX in this study included moderate to severe fatigue, hematopoietic 
toxicity, nausea and diarrhea. In practice, individual practitioners and institutions have made 
changes to the FOLFIRINOX backbone to reduce these toxicities. How these changes may affect 
the endpoints of PFS and OS in FOLFIRINOX treated patients is not known. However, the 
overall poor tolerability of this regimen in various groups of patients, especially in older or 
poorer PS patients, makes this combination difficult to utilize in the majority of pancreatic 
patients, and therefore it is not universally accepted as first line treatment in metastatic patients. 
Its toxicities also make it a poor choice to combine with other drugs in new studies such as this 
one due to possible overlapping toxicity.  
 
2.6 
Paclitaxel Albumin-bound Particles (Nab-Paclitaxel)  
Nab-paclitaxel is a unique protein formulation of a non-crystalline, amorphous form of paclitaxel 
in an insoluble particle state.  Nab-paclitaxel has been developed to reduce the toxicities 
associated with Taxol (paclitaxel) Injection (in which paclitaxel - from the native crystalline 
form - is formulated with Cremophor EL/ethanol as the solvent) while maintaining or improving 
its chemotherapeutic effect.  Nab-paclitaxel has been approved for commercialization in 38 
countries, including the United States (US), Canada, the EU, Australia, China, India and Korea 
for the treatment of women with metastatic breast cancer.  Nab-paclitaxel alone and in 
combination chemotherapy is being evaluated in a number of cancers, including metastatic 
melanoma, non-small cell lung cancer, pancreatic cancer, and other solid tumors.   
 
A recent phase 3 clinical trial of nab-paclitaxel in combination with gemcitabine in treatment-
naïve patients with metastatic pancreatic cancer demonstrated a statistically significant 
improvement in overall survival compared to patients receiving gemcitabine alone [(median of 
8.5 vs. 6.7 months) (HR 0.72, P=0.000015)]. In the MPACT (Metastatic Pancreatic 
Adenocarcinoma Clinical Trial) study, nab-paclitaxel plus gemcitabine demonstrated a 59% 
increase in one-year survival (35% vs. 22%, p=0.0002), double the rate of survival at two years 
(9% vs. 4%, p=0.02), and an improvement in 3 year survival (4% vs. 0%) as compared to 
gemcitabine alone. Nab-paclitaxel plus gemcitabine also demonstrated a statistically significant 
improvement in key secondary endpoints compared to gemcitabine alone, including a 31% 
reduction in the risk of progression or death with a median progression-free survival (PFS) of 5.5 
vs. 3.7 months (HR 0.69, P=0.000024) and an overall response rate (ORR) of 23% compared to 
7% (response rate ratio of 3.19, p=1.1 x 10-10). 
 
The most common grade ≥ 3 treatment-related adverse events in the study for nab-paclitaxel plus 
gemcitabine vs. gemcitabine alone were neutropenia (38% vs. 27%), fatigue (17% vs. 7%), and 
neuropathy (17% vs. 1%). In the nab-paclitaxel plus gemcitabine arm, the median time to 

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neuropathy improvement was 29 days. There was no difference in serious life threatening 
toxicity (4% in each arm). 
 
No direct comparison of FOLFIRINOX to gemcitabine and nab-paclitaxel has been made to 
date, but because of its survival advantage and good tolerability, gemcitabine and nab-paclitaxel 
is the most widely accepted and utilized first line regimen in metastatic pancreatic cancer. 
 
2.7 
 Rationale for current study  
The observation that inhibition of IDO can augment traditional cytotoxic agents in vivo in 
murine models provides a rationale for examining it in combination with effective chemotherapy 
regimens in human subjects. In particular, the traditional resistance of adenocarcinoma of the 
pancreas to standard chemotherapies and its marked immune suppressive tumor 
microenvironment suggest that the biologic response modifier indoximod may be particularly 
interesting.  Recent data suggest that the chemotherapeutic regimen including gemcitabine plus 
nab-paclitaxel is associated with higher response rates and improved overall survival when 
compared to single agent gemcitabine.  This study seeks to examine the additional toxicity of the 
biologic response modifier indoximod to the backbone chemotherapy of gemcitabine plus nab-
paclitaxel and to identify a suitable dose of indoximod for future phase 2 and 3 studies. 
 
2.8 
 Rationale for Phase 1 design  
“Combination” clinical trials of novel biological or immunotherapy agents assess the safety 
and/or efficacy of a biologic or immunotherapeutic by treating patients with the investigational 
agent plus a standard-of-care (“backbone”) chemotherapy. While this addresses the ethical 
concern of treating patients with an investigational agent of unknown efficacy when a standard-
of-care chemotherapy (even of modest efficacy) is available, it complicates the assessment of the 
safety and efficacy of the investigational agent.  Phase 1 dose-escalation trials are especially 
difficult, since patients are generally treated at the MTD of the backbone therapy, which, by 
definition, already induces significant toxicity in approximately1/6 of patients (the target rate of 
the 3 + 3 dose-escalation trial design). Phase 1 and early phase 2 trials are typically not large 
enough to identify even a significant increase of a known backbone toxicity, so a simple 
randomized trial would be underpowered. We propose a Phase 1 dose-escalation trial of an 
immunotherapeutic agent that addresses these issues, by escalating against the effect of regimen-
limiting toxicity, i.e., toxicity induced by the immunotherapeutic agent that limits the 
administration of the backbone therapy.  Specifically, we define regimen-limiting toxicity (RLT) 
as a toxicity attributable to the immunotherapy agent that delays the planned administration of 
the next cycle of the backbone chemotherapy. RLT will usually include all the toxicities that are 
usually defined as dose-limiting (e.g., Grade 3) non-hematological toxicities and all Grade 4 and 
5 toxicities), in addition to less severe toxicities, but it is phenomenological in nature; if a 
patient’s next cycle of treatment is delayed because of an adverse event caused by treatment, that 
patient has experienced RLT, irrespective of the severity or nature of the causal toxicity. The 
goal of the trial will be to find the maximum dose of indoximod that does not induce RLT in 
more than 1/6 of patients treated with gemcitabine plus nab-paclitaxel.  The dose will be 
allocated using a standard Phase 1 design.  
 

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3.0 
STUDY POPULATION 
Potential patients will be identified from each investigator’s and co-investigators’ current clinic 
population at each participating institution, or will be referred by their own physicians. They will 
be approached and informed of the study by an individual who is involved in their care. No cold-
calling will occur, and no advertising will be used. The consent process will be carried out as a 
joint effort among the subject's physician, the study coordinator, and/or co-investigators on the 
study.  
 
3.1 
Inclusion Criteria:  
A patient will be eligible for inclusion in this study only if all of the following criteria are met:  
 
 Patient has definitive histologically or cytologically confirmed metastatic 
adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic 
adenocarcinoma will be made by integrating the histopathological data within the context 
of the clinical and radiographic data. Patients with islet cell or neuroendocrine neoplasms 
are excluded. 
 
 Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in the 
study. 
 
 Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4 
weeks prior to entry into the study (or MRI, if patient is allergic to CT contrast media). 
Patients cannot have nodal metastases alone even if such nodal metastases are formally 
considered M1 disease. 
 
 Life expectancy of greater than 3 months. 
 
 Male or non-pregnant and non-lactating female, and ≥18 years of age. 
 
 If a female patient is of child-bearing potential, as evidenced by regular menstrual 
periods, she must have a negative serum or urine pregnancy test (β-hCG) documented 
within 7 days prior to the first administration of study drug. 
 
 The effects of indoximod on the developing human fetus are unknown. For this reason 
and because indoximod may affect maternal immune tolerance of the fetus, sexually 
active women of child-bearing potential must agree to use two forms of contraception 
(hormonal and barrier method of birth control or abstinence) prior to study entry and for 
the duration of study participation. Use of contraception or abstinence should continue 
for a minimum of 1 month after completion of the study. Should a woman become 
pregnant or suspect she is pregnant while participating in this study, she should 
discontinue the study drug and inform her treating physician immediately. Also men 
should be discouraged from fathering children while on treatment. 
 

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 Patients must have received no previous radiotherapy, surgery, chemotherapy or 
investigational therapy for the treatment of metastatic disease. 
 
 Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is allowed, 
provided at least 6 months have elapsed since completion of the last dose and no 
lingering toxicities are present. 
 
  Patients who have not received any other immunomodulatory therapies (including 
vaccines) as treatment for this or any other cancer. 
 
 Patient has adequate biological parameters as demonstrated by the following blood 
counts at Baseline (obtained ≤14 days prior to treatment initiation): 
 
 Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 
 Platelet count ≥ 75,000/mm3  
 Hemoglobin (Hgb) ≥ 9 g/dL. 
 
 Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to 
treatment initiation): 
 
 AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver 
metastases are clearly present, then ≤ 5 × ULN is allowed 
 Albumin ≥ 2.8 g/dL 
 Total bilirubin ≤ ULN, patients with known Gilbert’s syndrome allowed up to 3 x 
ULN. 
 Serum creatinine within normal limits or calculated clearance ≥ 60 mL/min/1.73 
m2 for patients with serum creatinine levels above or below the institutional normal 
value 
 
 Patient has acceptable coagulation studies (obtained ≤ 14 days prior to randomization) as 
demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within 
normal limits (± 15%). If the patient is on coumadin we suggest switching the patient to a 
low molecular weight heparin product including enoxaparin (Lovenox) and fondiparinux 
(Arixtra), but if not feasible then INR must be < 3. 
 
 Patient has no clinically significant abnormalities in urinalysis results (obtained ≤ 14 days 
prior to enrollment). 
 
 Patient has a Karnofsky performance status (KPS) ≥ 70. 
 
 Patients should be asymptomatic for jaundice prior to enrollment. 
 
 Pain symptoms should be stable and should not require modifications in analgesic 
management prior to enrollment. 
 

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 Ability to understand and the willingness to sign a written informed consent document. 
 
 For the Phase 2 expansion cohort, patient must have a target tumor lesion that is easily 
amenable to percutaneous core needle biopsy. Lesions that can be imaged by ultrasound 
are strongly preferred. Only percutaneous biopsies are allowed, biopsies via endoscopic 
approaches are not allowed. Lung lesions are not allowed due to the high risk of 
complication (pneumothorax) with repeat core needle biopsy. 
 
3.2 
Exclusion Criteria:  
A patient will not be eligible for inclusion in this study if any of the following criteria apply: 
 
 Patients may not be receiving (or received prior to enrollment) any other investigational 
agents for metastatic disease. 
 
 Patient has known brain metastases,  
 
 Patient has only locally advanced disease. 
 
 Lymph node only metastases even if considered M1 disease by official staging criteria. 
 
 Ascites of any measurable amount or any clinical significance. Patients who have 
previously had ascites that has been drained are also ineligible. Trace ascites on a CT 
scan is allowed. 
 
 History of malignancy in the last 3 years. Patients with prior history of in situ cancer or 
basal or squamous cell skin cancer are eligible. Patients with other malignancies are 
eligible if they were cured by surgery alone or surgery plus radiotherapy and have been 
continuously disease-free for at least 3 years. 
 
 Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic 
therapy. 
 
 Patient has known historical or active infection with HIV, hepatitis B, or hepatitis C. 
 
 Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic dermatitis, 
asthma, IBD, M.S., uveitis, vasculitis), chronic inflammatory condition, or any condition 
requiring concurrent use of any systemic immunosupressants or steroids for any reason 
would be excluded from the study. Any patient with an allo-transplant of any kind would 
be excluded as well. This would include those with a xenograft heart valve to avoid the 
potential risk of any immune reaction causing valvular degeneration. Mild-intermittent 
asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will 
not be excluded. 
 

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 Patient has undergone major surgery, other than diagnostic surgery (i.e., surgery done to 
obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 
of treatment in this study. 
 
 Patient has a history of allergy or hypersensitivity to any of the study drugs or any of 
their excipients. 
 
 Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive 
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social 
situations that would limit compliance with study requirements. 
 
 Pregnant women are excluded from this study, breastfeeding should be discontinued. 
 
3.3 
Inclusion of Women and Minorities 
Both men and women of all races and ethnic groups are eligible for this trial. 
 
3.4 
On Study Tests 
3.4.1 
Baseline Assessment 
 Patients must be entered into the trial and start treatment within 8 weeks of diagnosis of 
metastatic pancreatic cancer.  
 
 Baseline imaging study (high quality spiral CT with intravenous contrast or MRI if CT 
contrast allergic) demonstrating measurable metastatic disease must be performed ≤ 30 
days prior to entry into study. 
 
 If no PET scan has been performed as part of routine clinical care ≤ 4 weeks prior to 
entry into the study, one may be performed after entry but prior to the initiation of any 
treatment. Up to thirty patients will undergo PET evaluation at selected institutions. 
These are being done for research purposes only and are not intended to impact or direct 
treatment within the scope of this protocol. 
 
 If patient has any evidence (imaging or biochemical) of biliary obstruction or impending 
biliary obstruction, a biliary stent (preferably metal) shall be placed prior to entry in the 
study. If a stent becomes occluded while on trial, it shall be replaced with a metal stent 
unless there is a clear contra-indication. 
 
3.4.2 
Additional On-Study Tests 
On-Study and Eligibility Tests will include (See Section 13.0 Study Calendar for details) 
 
 Baseline history and complete physical examination (to include height and weight) within 
14 days prior to initiating therapy.  
 

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 Serum chemistries including BUN, creatinine, albumin, and glucose; electrolytes 
including sodium, potassium, and calcium; liver function tests including total bilirubin, 
AST (SGOT), ALT (SGPT), and alkaline phosphatase to be done within 14 days prior to 
initiating therapy. 
 
 HCG pregnancy test (serum or urine) to be done within 7 days prior to first treatment for 
all women with child-bearing potential 
 
 Baseline ECG 
 
 CBC with platelets and 5-part differential (to include neutrophils, lymphocytes, 
eosinophils, basophils, and monocytes) to be done within 14 days prior to initiating 
therapy. 
 
 Blood (approximately 4 mL) for measurement of 
 at baseline 
 
 Bloods for correlative studies. See section 12.0. 
 
 For Phase 2 expansion cohort, pre-treatment biopsies are required. The lesion to be 
biopsied must be accessible via percutaneous core needle. No endoscopic or laparoscopic 
biopsies are allowed. No lung lesions are allowed. Lesions that can be imaged by 
ultrasound are strongly preferred. If a lesion can be imaged by both ultrasound and CT 
scan, ultrasound is required unless there are special circumstances. Such cases must be 
discussed in advance with either the overall study PI or the medical monitor. Each biopsy 
must consist of four individual core biopsies. Details of biopsy handling are included in 
the lab manual. A paired on-treatment biopsy of the same lesion performed in the same 
fashion is also required during study week 8. 
4.0 
STUDY DESIGN AND METHODS 
4.1 
Study Design  
This is a Phase 1/2 trial designed to evaluate the combination of the immunotherapeutic agent 
indoximod and the standard of care chemotherapy gemcitabine plus nab-paclitaxel in patients 
with metastatic adenocarcinoma of the pancreas. The phase 1 portion is designed to identify the 
regimen-limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination. 
The phase 2 portion of the study will evaluate the potential efficacy of this combination. All 
patients will receive the standard 28-day gemcitabine plus nab-paclitaxel regimen. Twice daily 
oral indoximod will be administered concurrently in continuous 28 day cycles. The Phase 2 
expansion cohort will require paired biopsies prior to treatment and prior to the start of Cycle 2. 
Drug dosing will be the same as in Phase 2. 
 
In the phase 1 portion, dose escalation of indoximod will begin at 600mg twice daily and 
potentially escalate to 1200 mg twice daily. There will be no intra-subject dose escalation.  
Regimen-limiting toxicity will be considered as those toxicities related to indoximod that 
significantly limit the administration of the backbone chemotherapy gemcitabine plus nab-

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paclitaxel.  The period for determination of dose-limiting toxicities will be the initial 28 days of 
treatment.  The recommended phase 2 dose will include an assessment of toxicities that occur at 
later time points. 
 
Once a RP2D is determined, the phase 2 portion of the study will be initiated. In both phase 1 
and phase 2, every 2 cycles patients will have repeat imaging to assess response. Corollary 
biomarkers will be assessed at the same interval as will PET-CT after the 1st 8 week cycle. Up to 
18 patients will be enrolled in the phase 1 portion of the study and 80 patients will be enrolled in 
the phase 2 portion. 
 
 
4.2 
 Phase 1 treatment plan 
The phase 1 portion of the study will be a dose escalation study of indoximod against the 
standard gemcitabine plus nab-paclitaxel 4 week schedule. A standard 3+3 dose escalation 
design will be used. Escalation will be done against regimen limiting toxicities as described in 
sections 4.2.1 and 4.2.2. 
 
4.2.1 
 Definition of Regimen-Limiting Toxicity (RLT)  
The standard chemotherapy regimen gemcitabine plus nab-paclitaxel is one of the new backbone 
chemotherapy regimens to which new agents will be added for patients with adenocarcinoma of 
the pancreas.  To describe the safety and determine a RP2D of the new agent indoximod in 
combination with gemcitabine plus nab-paclitaxel, it is necessary to determine the attribution of 
all toxicities. However, when gemcitabine plus nab-paclitaxel is administered as standard 
regimen, it is associated with significant toxicities [9] that may confound efforts to define the 
true toxicity of new agents added to this backbone.  The danger is that the high rate of toxicity of 
the backbone regimen will result in an unacceptably high rate of rejecting all dose levels of new 
agents. It has been recommended in these situations that a “pragmatic” approach be adopted for 
determining any additional toxicity due to the test agent [10].  In this approach, only grade 3 and 
4 toxicities that are attributable to the test agent (indoximod) and result in the delay of the 
administration of the backbone chemotherapy, gemcitabine plus nab-paclitaxel, will be 
considered as regimen limiting.  Thus, for purposes of the dose escalation in this trial, Regimen 
Limiting Toxicity will be defined as: 
 
 Any grade 4 non-hematological toxicity that is related to indoximod, with the exception 
of alopecia or nausea;  
 
 Any grade 3 non-hematological toxicity that is related to indoximod that results in the 
delay of administration of the backbone chemotherapy (gemcitabine plus nab-paclitaxel) 
by more than 4 weeks; 
 
 Grade 4 thrombocytopenia (<25,000/µL) attributable to indoximod that results in the 
delay of administration of the backbone chemotherapy for more than 4 weeks; 
 
 Grade 4 (<500/µL) neutropenia lasting more than 7 days, or Grade 3 (<1000/µL) febrile 
neutropenia, attributable to indoximod;  

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 Delay in starting the second cycle of the backbone therapy by more than 4 weeks due to 
any additional toxicities attributable to test agent indoximod. 
 
AEs not known and expected from gemcitabine plus nab-paclitaxel and not seen in phase 1/2 
indoximod studies will be considered regimen associated toxicities initially. Any grade 3 or 
higher regimen toxicity of this nature mandates a conference call within the next 3 business days 
between investigators and sponsor to discuss attribution and response. 
 
4.2.2 
Dose Escalation Rules  
Each cycle is 28 days. Patients will continue until they experience disease progression or 
toxicity.  
 
The different dose-levels are defined in Table 1. 
 
Table1. Dose levels (Phase 1 portion). 
 
 
Patients will be assigned in cohorts of three.  
 
Dose escalation will occur according to the following schema: 
 
Number of Patients with RLT at a 
Given Dose Level 
Escalation Decision Rule 
0 out of 3 
Enroll next three patients at the next higher 
dose level. 
≥2 out of 3 
Dose escalation will be stopped. Next lower 
dose will be declared MTD. If only three 
patients were enrolled at lower dose level, an 
additional three patients will be enrolled. 
1 out of 3 
3 more patients are enrolled at this dose. 
 If 0 of 3 of these experience a RLT, 
escalate to next level 
 If 1 or more of these experience RLT, 
dose escalation is stopped and next lower 
dose is declared MTD 
 
MTD will be declared to be the highest dose at which ≤ 1 out of 6 patients experiences a RLT. If 
0 out of 3 patients experience a RLT at dose level 3, the cohort will be expanded to 6 to assure 
that ≤ 1 out of 6 patients experience a RLT at that dose and establish it as the RP2D. MTD in this 
Dose Level Indoximod DOSE (oral)
Nab-paclitaxel (IV) 
Gemcitabine 
1 
600 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000  mg/m2 weekly x 3 
2 
1000 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000  mg/m2 weekly x 3 
3 
1200 mg BID x 28 days 
125 mg/m2 weekly x 3 
1000  mg/m2 weekly x 3 

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context is considered a function of indoximod in this combination and not a MTD for indoximod 
in any other context / combination. 
 
The period for determination of dose-limiting toxicities will be the initial 28 days of treatment.  
The recommended phase 2 dose will include an assessment of toxicities that occur at later time 
points. 
 
The initial dose of Indoximod will be 600 mg BID. If a RLT is reported at Dose Level 1, a lower 
dose cohort may be added after consultation between the Investigators, Medical Monitor and 
Sponsor, depending on the cumulative safety data. The protocol will be amended at that time 
accordingly. 
 
After the first two cycles of backbone chemotherapy, interval assessments will be performed. 
These will include CT or MRI (consistent with patient’s baseline imaging modality) as well as 
PET in up to 30 patients at selected institutions for research purposes. Biochemical assessments 
will be performed as well as per the study calendar. Patients continuing on treatment will have 
imaging and biochemical assessment after every two cycles (with research PET performed after 
the first 2 cycles only). 
 
Treatment may continue until patient has a treatment limiting toxicity, progression of disease, 
withdrawals consent, or is considered to no longer be in adequate physical condition for 
additional therapy by the treating physician. 
 
4.3 
Phase 2 Treatment Plan 
Once a RP2D is determined, treatment will commence with oral indoximod concurrent with the 
first backbone chemotherapy cycle. 
 
Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral 
indoximod will continue throughout. 
 
After the first two cycles of backbone chemotherapy, interval assessments will be performed. 
These will include CT or MRI (consistent with patient’s baseline imaging modality) as well as 
PET in up to 30 patients at selected institutions for research purposes. Biochemical assessments 
will be performed as well as per the study calendar. Patients continuing on treatment will have 
imaging and biochemical assessment after every two cycles (with research PET performed after 
the first 2 cycles only). 
 
Treatment may continue until patient has treatment limiting toxicity, progression of disease, 
withdrawals consent, or is considered to no longer be in adequate physical condition for 
additional therapy by the treating physician. 
 
4.4 
Phase 2 Expansion Cohort Treatment Plan 
Once the Phase 2 cohort fills, additional patients will be enrolled in an expansion cohort that 
requires paired pre-treatment and on-treatment biopsies of the same lesion. Biopsies must be 
done percutaneously, preferably by ultrasound guidance. No endoscopic or laparoscopic biopsies 

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are allowed. No lung lesions are allowed due to the high risk of complication (pneumothorax) 
with multiple core needle biopsies. 
 
Each biopsy is to consist of four core needle samples of tumor. No FNA’s are allowed. Patients 
have to have a lesion that can be biopsied with a core needle to be eligible. Lesions that can be 
imaged by ultrasound are strongly preferred. If a lesion can be imaged by both ultrasound and 
CT scan, ultrasound is required unless there are special circumstances. Such cases must be 
discussed in advance with either the overall study PI or the medical monitor. Details of biopsy 
handling are included in the lab manual. 
 
The first biopsy is to be done prior to study treatment. The second biopsy is to be done during 
study week 8 (Cycle 2 week 4). 
 
Study treatment in the Phase 2 expansion will otherwise follow the treatment plan for Phase 2. 
 
4.5 
Follow-up Phase 
Once patients are no longer receiving treatment or are removed from study treatment for any of 
the reasons listed in sections 6 or 7, they will be followed monthly for a period of 6 months. 
Follow up may consist of either in-person or by telephone assessment as the patient’s clinical 
condition dictates. 
 
Once 6 months have passed from the end of treatment, patients will be followed every 3 months 
until death or three years has elapsed. 
5.0 
REGISTRATION PROCEDURES 
5.1 
Registration Process 
All patients must be registered on study before beginning therapy. 
 
 
All patients must have a: (1) signed Informed Consent Document and, (2) a completed 
Eligibility Checklist Form before registration on the study. To register a subject for this 
protocol, an authorized physician or their designee must FAX or EMAIL the subject 
information to the NewLink Genetics Registration Office or the site’s designated CRA 
between the hours of 8:30 A.M. and 5:00 P.M. Central Standard Time, Monday through 
Friday. (FAX: (515) 296-3556; EMAIL: PatientRegistrations@linkp.com). No evening, 
weekend or holiday registrations will be permitted. Once eligibility is confirmed, NewLink 
will FAX or EMAIL a confirmation of registration to the site.  
 
A file of copies of all reports, laboratory studies and other pertinent information documenting 
the subject’s eligibility for study will be maintained in the Clinical Research Office of 
NewLink Genetics Corporation. 

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for all remaining cycles unless otherwise not indicated. Choice of growth factor is at the 
investigator's discretion 
 
 Erythropoiesis-stimulating agents (ESA) can be utilized as per institutional guidelines 
and as per the ESA APPRISE (Assisting Providers and cancer Patients with Risk 
Information for the Safe use of ESAs) program requirements. 
 
 Because of the risk of sepsis with gemcitabine plus nab-paclitaxel, especially in those 
patients who have biliary stents due to biliary obstruction, patients must be instructed to 
begin taking either ciprofloxacin 500mg BID orally (or amoxicillin/clavulanate 875 BID 
orally if allergic to ciprofloxacin or similar drugs) for any fever  > 100. 5 deg F (38.3 C). 
They should then call their treating physician and be evaluated as soon as clinically 
indicated. 
 
 Concomitant medications should be avoided with the exception of analgesics (only 
acetaminophen or narcotics may be given for pain), chronic treatments for concomitant 
medical conditions, or agents required for life threatening medical problems. 
 
 No additional chemotherapy, immunotherapy, or other anti-tumor therapy is permitted 
during the study. 
 
6.5 
Duration of Therapy  
In the absence of treatment delays due to adverse event(s), treatment may continue for until one 
of the following criteria applies 
 
 Unacceptable adverse event(s) 
 Disease progression per immune-related criteria AND RECIST criteria 
 Intercurrent illness that prevents further administration of treatment 
 Patient decides to withdraw from the study 
 Patient inability to be compliant with study treatment in opinion of investigator defined 
as missing infusional treatments for non-medical reasons or complying with oral 
treatments below an 85% threshold on two sequential study visits 
 General or specific changes in the patient's condition render the patient unacceptable for 
further treatment in the judgment of the investigator 
 
7.0 
KNOWN TOXICITIES AND DOSING DELAYS/DOSE MODIFICATIONS 
7.1 
Indoximod Toxicities   
The most common adverse reactions (>10% incidence) are: fatigue, nausea, vomiting, diarrhea, 
anorexia, and anemia. 
 

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The most common Grade 3 to 4 hematologic laboratory abnormalities that have developed 
during treatment with indoximod are thrombocytopenia, neutropenia, anemia, lymphopenia and 
leukopenia. 
 
7.2 
Gemcitabine Toxicities 
Hematologic - In studies in pancreatic cancer, myelosuppression is the dose-limiting toxicity 
with gemcitabine, but <1% of patients discontinued therapy for anemia, leukopenia, or 
thrombocytopenia.  Red blood cell transfusions were required by 19% of patients.  The incidence 
of sepsis was less than 1%.  Petechiae or mild blood loss (hemorrhage), from any cause, was 
reported in 16% of patients; less than 1% of patients required platelet transfusions.  Patients 
should be monitored for myelosuppression during gemcitabine therapy and dosage modified or 
suspended according to the degree of hematologic toxicity. Rare (<1%) incidence of autoimmune 
related thrombocytopenias have been described, which can be life threatening. 
 
Gastrointestinal - Nausea and vomiting were commonly reported (69%) but were usually of 
mild to moderate severity.  Severe nausea and vomiting (World Health Organization [WHO] 
Grade 3/4) occurred in <15% of patients.  Diarrhea was reported by 19% of patients, and 
stomatitis by 11% of patients.   
 
Hepatic - In clinical trials, Gemzar was associated with transient elevations of one or both serum 
transaminases in approximately 70% of patients, but there was no evidence of increasing hepatic 
toxicity with either longer duration of exposure to gemcitabine or with greater total cumulative 
dose.  Serious hepatotoxicity, including liver failure and death, has been reported very rarely in 
patients receiving gemcitabine.   
 
Renal - In clinical trials, mild proteinuria and hematuria were commonly reported.  Hemolytic 
Uremic Syndrome (HUS) has been reported rarely (0.25%) with the use of gemcitabine.  Renal 
failure may not be reversible even with discontinuation of therapy and dialysis may be required. 
 
Fever - The overall incidence of fever was 41%.  This is in contrast to the incidence of infection 
(16%) and indicates that gemcitabine may cause fever in the absence of clinical infection.  Fever 
was frequently associated with other flu-like symptoms and was usually mild and clinically 
manageable.   
 
Rash - Rash was reported in 30% of patients.  The rash was typically a macular or finely 
granular maculopapular pruritic eruption of mild to moderate severity involving the trunk and 
extremities.  Pruritus was reported for 13% of patients.   
 
Pulmonary - In clinical trials, dyspnea, unrelated to underlying disease, has been reported in 
association with gemcitabine therapy.  Dyspnea was occasionally accompanied by 
bronchospasm.  Pulmonary toxicity has been reported with the use of gemcitabine.  The etiology 
of these effects is unknown.  If such effects develop, gemcitabine should be discontinued.  Early 
use of supportive care measures may help ameliorate these conditions.   
 
Edema - Edema (13%), peripheral edema (20%), and generalized edema (<1%) were reported.  
Less than 1% of patients discontinued due to edema.   

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Flu-like Symptoms - “Flu syndrome” was reported for 19% of patients.  Individual symptoms of 
fever, asthenia, anorexia, headache, cough, chills, and myalgia were commonly reported.  Fever 
and asthenia were also reported frequently as isolated symptoms.  Insomnia, rhinitis, sweating, 
and malaise were reported infrequently.  Less than 1% of patients discontinued due to flu-like 
symptoms.   
 
Infection - Infections were reported for 16% of patients.  Sepsis was rarely reported.   
 
Alopecia - Hair loss, usually minimal, was reported by 15% of patients.   
 
Neurotoxicity - There was a 10% incidence of mild paresthesias and a <1% rate of severe 
paresthesias.   
 
Sepsis 
 
Interstitial pneumonitis – Rare but can be life threatening and requires removal from study. 
 
7.3 
Nab-paclitaxel Toxicities 
Myelosuppression, predominantly neutropenia - Grade 4 neutropenia was reported and 
typically resolved in <7 days and did not require colony stimulating factor support. 
 
Peripheral neuropathy, predominantly sensory - Grade 3 peripheral neuropathy was reported 
and typically improved to Grade 1 or 2 within 21 days of interrupting the dose.  Following 
resolution of the peripheral neuropathy to acceptable levels, clinicians were able to restart dosing 
at a lower dose level. 
 
Nausea and vomiting - Nausea and vomiting were seen, typically at Grade 1 or 2 levels.  This 
AE responded well to standard anti-emetic regimens. 
 
Myalgias and arthralgias - Myalgias and arthralgias were reported and typically were Grade 1 
or 2; these were responsive to standard acetaminophen-containing medication. 
 
Mucositis - Mucositis was reported typically Grade 1 or 2.  It was not dose-limiting. 
 
Alopecia - Alopecia was reported by most patients and was similar to that seen with Taxol. 
 
Sepsis 
 
Interstitial Pneumonitis – Rare but can be life threatening and requires removal from study. 
 
7.4 
Dose Omissions for Indoximod 
Any missed doses are not made up. Dosing continues on the next dose. 
 

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7.5 
Dose Omissions for Gemcitabine and/or Nab-paclitaxel 
Day 1 dose missed: If a dose is held or missed that was to be given on Day 1 of a cycle, that 
cycle will not begin until the day the first dose of the cycle is given. 
 
Day 8 dose missed: If a Day 8 dose is missed, the cycle continues and that dose is not given. The 
dose is not made up and the cycle remains 28 days. 
 
Day 15 dose missed: If a day 15 dose is missed, the ensuing week (days 15-21) are considered to 
be the rest week and the cycle is shortened to 21 days. The next cycle is unaffected. 
 
The maximum days between doses should never exceed 28 days (except for peripheral 
neuropathy, see below). 
 
7.6 
Dose Modification for Indoximod 
In general, indoximod was very well tolerated in both phase 1 trials and seldom required any 
dose reductions. If a dose reduction is deemed necessary due to intolerance from taking the 
required number of pills or grade 3-4 nausea, a one-time dose reduction of 200 mg is permitted. 
If this is not tolerated, then discontinuation of the study treatment is required however, all 
patients will still be followed per section 4.4. 
 
7.7 
Dose Modifications for Gemcitabine and/or Nab-paclitaxel 
Doses will be reduced for hematologic and other toxicities.  Dose adjustments are to be made 
according to the system showing the greatest degree of toxicity.  Toxicities will be graded using 
the NCI CTCAE Version 4.0. 
 
Two levels of dose modifications are permitted according to the criteria below.  If a toxicity 
requiring dose modification occurs following the second dose reduction of either study drug, 
further treatment should be discontinued. 
 
Table 3: 
Dose Modifications 
Dose Level 
Nab-paclitaxel Dose (mg/m2)a
Gemcitabine (mg/m2)b 
Study Dose 
125 
1000 
-1 
100 
800 
-2 
75 
600 
Dose reductions may or may not be concomitant.  Please refer to Table 4 and Table 5 for specific recommendations 
regarding dose modifications for Day 1 of each cycle for hematologic and non-hematologic toxicity, respectively.  
Please refer to Table 6 and Table 7 for specific recommendations regarding dose modifications within a cycle for 
hematologic and non-hematologic toxicities, respectively.  A maximum of 2 dose level reductions are allowed.   
 
Patients experiencing study drug-related toxicities that require a delay in scheduled nab-
paclitaxel or gemcitabine dosing for  21 days will be discontinued from further treatment in this 
study (except for peripheral neuropathy and edema; see below).  When a dose reduction is 
required, no dose re-escalation will be permitted for the duration of study treatment (except for 
peripheral neuropathy and edema and with the exception mentioned in Table 6 namely: on Day 

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15, re-escalation with granulocyte-colony stimulating factor (G-CSF) support is permitted, after 
a previous dose reduction on Day 8 of the same cycle). 
 
Dose Modifications at Day 1 
In the event dose modifications are required at the beginning of a cycle due to AEs or 
hematologic toxicities, doses of nab-paclitaxel and gemcitabine may be adjusted as detailed in 
Table 4 and Table 5 as presented below:  
 
Table 4: 
Dose Modifications for Day 1 of Each Cycle (Hematologic Toxicity) 
Treatment day counts and toxicity 
ANC 
 
Platelets 
Timing 
1.5 x 109/L 
And 
100 x 109/L 
Treat on time 
<1.5 x 109/L 
Or 
<100 x 109/L 
Delay by 1 week intervals until recovery
Key: ANC = Absolute neutrophil count. 
 
 
Table 5: 
Dose Modifications for Day 1 of Each Cycle (Non-Hematologic Toxicity) 
Non Hematologic Toxicity and/or Dose Hold with Previous Cycle 
Toxicity/dose held 
Gemcitabine + nab-paclitaxel dose this cycle 
Grade 0, 1 or 2 toxicity 
Same as Day 1 of previous cycle (except for Grade 2 
cutaneous toxicity where doses of gemcitabine and 
nab-paclitaxel should both be reduced to next lower 
dose level 
Grade 3 toxicity
i) 
Decrease gemcitabine and nab-paclitaxel to next lower 
dose level 
Grade 4 toxicity
ii) 
Off protocol treatment 
Dose held in 2 previous consecutive 
cycles 
Decrease gemcitabine to next lower dose level and 
continue throughout the rest of treatment 
Key: CTCAE = Common terminology criteria for adverse events.   
i) If the toxicity only affects neuropathy, then only nab-paclitaxel should be reduced (please see Section 7.7). 
ii) Pulmonary embolism (a Grade 4 toxicity in the CTCAE tables) if mild or a symptomatic, will be exempt from this 
requirement (please see Section 7.7).   
 
Dose Adjustments within a Treatment Cycle 
In the event that patients must have treatment delayed within a treatment cycle due to toxicities, 
those doses held during a cycle will not be made up.  Dose modifications due to hematologic 
toxicity (as represented by the blood counts and toxicities, below) within a treatment cycle 
should be adjusted as outlined in Table 6. 
 

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Table 6: 
Dose Modifications for Hematologic Toxicity within a Cycle 
 
Day 8 
Blood Counts 
Day 8 
Nab-paclitaxel 
Day 8 
Gemcitabine 
Day 15 
Blood Counts 
Day 15 
Nab-paclitaxel 
Day 15 
Gemcitabine
Any Day 
Nab-paclitaxel 
Any Day 
Gemcitabine 
ANC >1000  
and 
Platelets 
≥75,000 
100% 
100% 
ANC >1000 and 
Platelets ≥75,000 
100% 
100% 
 
 
ANC 500-1000 or 
Platelets 50,000-
74,999 
Full Dose (treat 
on time)  
+ G-CSFa 
Full Dose 
(treat on 
time)  
+ G-CSFa 
ANC <500 or 
Platelets <50,000 
Hold + G-CSFa 
Hold + 
G-CSFa 
ANC 500- 
1000 b 
or 
Platelets 
50,000-74,999 
Decrease dose 
by 1 level (treat 
on time) 
Decrease dose 
by 1 level 
(treat on time) 
ANC >1000 and 
Platelets ≥75,000 
Return to 
Previous Dose 
level (treat on 
time) + G-CSFa 
Return to 
Previous 
Dose Level 
(treat on 
time) + 
G-CSFa 
 
 
ANC 500-1000 or 
Platelets 50,000-
74,999 
Same Dose (as 
Day 8, treat on 
time) + G-CSFa 
Same Dose 
(as Day 8, 
treat on time) 
+ G-CSFa 
ANC <500 or 
Platelets <50,000 
Hold + G-CSFa 
Hold + 
G-CSFa 
ANC <500a 
or 
Platelets 
<50,000 
Hold 
Hold 
ANC >1000 and 
Platelets ≥75,000 
Decrease Day 8 
dose by 1 level 
(treat on time) + 
G-CSFa 
Decrease 
Day 8 dose 
by 1 level 
(treat on 
time) + 
G-CSFa 
 
 
 
 
 
ANC 500-1000 or 
Platelets 50,000-
74,999 
Decrease Day 8 
dose by 1 level 
(treat on time)  
+ G-CSFa 
Decrease 
Day 8 dose 
by 1 level 
(treat on 
time)  
+ G-CSFa 
 
 
 
 

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Day 8 
Blood Counts 
Day 8 
Nab-paclitaxel 
Day 8 
Gemcitabine 
Day 15 
Blood Counts 
Day 15 
Nab-paclitaxel 
Day 15 
Gemcitabine 
Any Day 
Nab-paclitaxel 
Any Day 
Gemcitabine 
 
 
 
ANC <500 or 
Platelets <50,000 
Hold + G-CSFa 
Hold + 
G-CSFa 
 
 
Febrile 
Neutropenia 
(Grade 3 or 4)c 
 
 
 
 
 
Hold.  Upon 
resuming 
dosing, 
decrease to 
next lower level 
and do not 
re-escalate 
throughout the 
rest of 
treatment. 
Hold.  Upon 
resuming 
dosing, 
decrease to 
next lower 
dose level and 
do not 
re-escalate 
throughout 
the rest of 
treatment. 
Recurrent  
Febrile 
Neutropenia 
(Grade 3 or 4)b 
 
 
 
 
 
Decrease to 
next lower dose 
level and do not 
re-escalate 
throughout the 
rest of 
treatment. 
Decrease 2 
dose levels 
(to 
600 mg/m2) 
and do not 
re-escalate 
throughout 
the rest of 
treatment. 
 
Table 6: Dose Modifications for Hematologic Toxicity within a Cycle  
Abbreviations:  ANC = Absolute neutrophil count; G-CSF = Granulocyte colony stimulating factor. 
a  G-CSF is optional if descent only affects platelets. 
b  If patients do not experience resolution of neutropenia within 21 days, despite uninterrupted G-CSF treatment, study treatment will be discontinued. 
c  Febrile patients (regardless of neutrophil count) should have their chemotherapy treatment interrupted.  A full sepsis diagnostic work-up should be performed while 
continuing broad spectrum antibiotics.  If cultures are positive, the antibiotic may or may not be changed, depending on the sensitivity profile of the isolated organism.  
Patients with persisting fever after 3 weeks, despite uninterrupted antibiotic treatment, will discontinue study treatment.  Febrile neutropenic patients can also receive G-
CSF, in addition to antibiotic treatment, to hasten the resolution of their febrile neutropenia (following current institutional guidelines).  In all cases, blood counts must 
have returned to baseline levels before resuming chemotherapy treatment. 

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Dose modifications may also be made for non-hematological toxicity within a cycle as specified 
in Table 7. 
 
Table 7: 
Dose Modifications for Non-Hematological Toxicity within a Cycle 
CTCAE Grade 
Percent of Day 1 
Nab-paclitaxel + Gemcitabine Dose 
0-2  
(and Grade 3 nausea/vomiting and alopecia) 
100%a 
3  
(except nausea/vomiting and alopecia) 
Hold either one or both drugs
a until resolution 
to ≤Grade 1.  Then resume treatment at the 
next lower dose level. 
4 
Holdb , c 
Abbreviations:  CTCAE = Common terminology criteria for adverse events. 
a: Except for cutaneous toxicity: please see below. 
b: This decision as to which drug should be modified will depend upon the type of non-hematologic toxicity seen 
and which course is medically most sound in the judgment of the physician/investigator. 
c: Pulmonary embolism (a Grade 4 toxicity in the CTCAE tables) if mild or asymptomatic, will be exempt from this 
requirement (please see below). 
 
Peripheral Neuropathy   
Nab-paclitaxel treatment should be withheld in patients who experience grade 3 or worse 
peripheral neuropathy.  Gemcitabine and indoximod administration can continue during this 
period.  Nab-paclitaxel treatment may be resumed at the next lower dose level in subsequent 
cycles if  the peripheral neuropathy improves to grade 1 or better.  Patients experiencing 
peripheral neuropathy that requires a delay in scheduled nab-paclitaxel dosing for ≥ 21 days will 
discontinue study treatment through treatment cycle 4. If a patient has completed 4 or more 
cycles of study treatment, then patients may continue on study treatment cycles of indoximod 
and gemcitabine alone. If the peripheral neuropathy improves to grade 1 or better during 
subsequent treatment cycles, nab-paclitaxel may be resumed as part of study treatment at the 
discretion of the treating physician. The time to resolution to grade 1 should be the adverse event 
duration used for adverse event reporting. 
 
Edema 
Patients who have completed 4 or more cycles of study treatment and experience clinically 
significant edema can continue on with study treatment cycles consisting of indoximod and 
gemcitabine alone. Nab-paclitaxel can be resumed as part of the study regimen at the discretion 
of the treating physician if the edema improves to grade 1 or better during subsequent study 
treatment cycles. 
 
Cutaneous Toxicity 
Patients who develop grade 2 or 3 cutaneous toxicity should have their dose reduced to the next 
lower dose level for both drugs.  If the patient continues to experience these reactions, despite 
dose reduction, treatment should be discontinued.  Patients who develop grade 4 cutaneous 
toxicity should have treatment discontinued. 
 

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Gastrointestinal Toxicity 
If grade 3 mucositis or diarrhea occurs, study drug should be withheld until resolution to grade 1 
or better, then reinstituted at the next lower dose level of both drugs.  Patients who develop grade 
4 mucositis or diarrhea should have treatment discontinued. 
 
Pulmonary Embolism 
Asymptomatic or clinically mild pulmonary embolism can be treated with low-molecular-weight 
heparin without interruption of therapy.  Moderate to severe pulmonary embolism will require 
permanent discontinuation of treatment. 
 
Interstitial Pneumonitis 
During study participation, patients should be carefully monitored for signs and symptoms of 
pneumonitis (i.e., episodes of transient or repeated dyspnea with unproductive persistent cough 
or fever) and, if observed, immediate clinical evaluation and timely institution of appropriate 
management (emphasizing the need for corticosteroids if an infectious process has been ruled out 
as well as appropriate ventilation and oxygen support when required).  Administration of all 
agents administered under this protocol should be permanently discontinued upon making a 
diagnosis of interstitial pneumonitis. 
 
Colony Stimulating Factor Administration 
Colony stimulating factors may Fe given according to institutional guidelines for the treatment of 
neutropenic fever or infections associated with neutropenia and for the prevention of febrile 
neutropenia in patients with an ANC <500 cells/µL.  Patients not experiencing resolution of 
neutropenia within 21 days, despite uninterrupted G-CSF treatment, will discontinue study 
treatment. 
 
Prophylaxis Against Sepsis 
Due to the incidences of non-neutropenic sepsis, at the first occurrence of fever ≥ 38.5 °C 
(regardless of neutrophil count), institution of ciprofloxacin (500 mg orally, twice daily)—or 
amoxicillin/clavulanate (Augmentin®, 500 mg orally, 2-3 times daily) in patients with allergy to 
fluoroquinolones—should be initiated.  On their first visit, patients should be provided with 
enough ciprofloxacin (or the alternative antibiotic) for use at home, and they should be instructed 
to begin taking it when they first record a temperature of ≥ 38.5 °C (or if they feel they are 
developing a fever and a thermometer is not available).  They should also immediately contact 
their physician for guidance on where to go for blood counts to be evaluated for sepsis as soon as 
possible.  Hospitalization or evaluation in the emergency room may be required depending on 
the clinical presentation. Further treatment and duration of anti-biotic therapy is to be determined 
by the treating physician, 
 
Hypersensitivity Reactions 
Hypersensitivity reactions are not expected with either nab-paclitaxel or gemcitabine.  If they do 
occur, minor symptoms such as flushing, skin reactions, dyspnea, hypotension, or tachycardia 
may require temporary interruption of the infusion.  However, severe reactions, such as 
hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized 

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Route of Administration: Oral 
 
Agent Ordering and Agent Accountability: As required by FDA regulations for all drug 
storage, procurement and usage are carefully monitored and documented.  The Principal 
Investigator will oversee this process and delegate responsibility as needed to conduct the trial 
under Good Clinical Practices.  A careful inventory is maintained at each of the clinical sites. A 
Study Agent Order Form will be made available to all participating sites.  The PI or designated 
individual will: 
 Complete a Study Agent Order form and send to NewLink Genetics.  NewLink will make 
the appropriate arrangements for the shipment of the drug from the manufacturer. 
 Upon receipt of the investigational drug, inventory the shipment ensuring that the 
information on the packing slip matches exactly with what has been sent to the site, 
including the amount, lot numbers and quantity, and document the results of this 
inventory on the provided inventory form. 
 Promptly bring any discrepancies, breakage or evidence of tampering to the attention of 
NewLink Genetics. 
 Retain a copy of the shipping inventory, packing slips, and documentation of inventory in 
the study’s records. 
 
8.2 
Gemcitabine pharmaceutical information: 
For complete details see package insert. 
 
Chemical Name: 2’-deoxy-2’2’-difluorocyti-dine monohydrochloride  
 
Mode of Action: Gemcitabine inhibits DNA synthesis in tumor cells by competing with 
deoxycytidine triphosphate for incorporation into DNA.  Gemcitabine metabolites also inhibit 
enzymes in DNA synthesis.  Finally, gemcitabine is masked from DNA repair enzymes with the 
addition of one additional nucleotide after gemcitabine is in the DNA chain. 
 
How Supplied: Gemcitabine is supplied in 200 mg and 1000 mg vials.  Two hundred mg vials 
are reconstituted in 5 cc sodium chloride then diluted to a concentration of as low as 0.1 mg/ml if 
necessary for infusion.  The dose is usually given over 30 minutes.  One thousand mg vials are 
reconstituted with 25 cc sodium chloride.  It is stored at room temperature until given.   
 
Storage: See package insert. 
 
Stability: See package insert. 
 
Route of Administration: Intravenous  
 
Supply: Commercially available 
 

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8.3 
Nab-paclitaxel pharmaceutical information: 
For complete information please see package insert 
 
Nab-paclitaxel is a Cremophor EL-free, albumin-bound paclitaxel particle with a mean size of 
approximately 130 nm 
 
Chemical Name: 5β,20-Epoxy-1,2α,4,7β,10β,13αhexahydroxytax-11-en-9-one 4,10-diacetate 2-
benzoate 13-ester with (2R,3S)-N-benzoyl-3phenylisoserin 
 
Mode of Action: Nab-paclitaxel is an antimicrotubule agent that promotes the assembly of 
microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. 
This stability results in the inhibition of the normal dynamic reorganization of the microtubule 
network that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces 
abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of 
microtubules during mitosis 
 
How Supplied: Nab-paclitaxel is supplied as a white to yellow, sterile, lyophilized powder for 
reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. 
Each single-use vial contains 100 mg of paclitaxel and approximately 900 mg of human albumin 
 
Storage: See package insert 
 
Stability: See package insert 
 
Route of Administration: Intravenous 
 
Supply: Commercially available 
 
9.0 
CLINICAL AND LABORATORY EVALUATIONS 
9.1 
Pretreatment Evaluations (See Study Calendar, Section 13.0):   
The following are the required pre-study evaluations: 
 History and physical examination including height, weight, vital signs and blood 
pressure, and determination of performance status by the ECOG scale (Appendix A). 
 
 Standard blood work (within 14 days) to include: CBC with differential, platelets, PT, 
PTT, total bilirubin, AST, ALT, alkaline phosphatase, sodium, potassium, bicarbonate, 
chloride, BUN, Cr, glucose, calcium, CA 19-9, CEA, and a pregnancy test if of child-
bearing potential as defined by ECOG.  These tests involve taking 1 tablespoon of venous 
blood. 

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 ECOG defines a female of childbearing potential as any woman (regardless of 
sexual orientation, having undergone a tubal ligation, or remaining celibate by 
choice) who meets the following criteria: 
1) Has not undergone a hysterectomy or bilateral oophorectomy; or 
2) Has not been naturally postmenopausal for at least 24 consecutive months (i.e., 
has had menses at any time in the preceding 24 consecutive months).  
 
Baseline imaging studies (within 30 days prior to study enrollment) including: 
 Contrast-enhanced, pancreas mass protocol helical CT scan of the chest, abdomen and 
pelvis. 
 
 If a patient has a known sensitivity to CT contrast media, high quality MRI with contrast 
may be used 
 
 PET scan in up to 30 patients at selected institutions for research purposes only will be 
performed no more than 30 days prior to study initiation. If PET has not been performed 
at time of enrollment into study, it must be performed prior to starting study treatment. 
 
Biopsy procedure to confirm pancreatic adenocarcinoma: 
 Methods may include fine-needle aspiration (FNA) via imaging guidance or during 
endoscopic ultrasound (EUS), endoscopic brushing at the time of ERCP, or laparoscopic 
directed needle biopsy. 
 
 Biopsy of distant disease site is preferred to make diagnosis of metastatic disease. 
 
 If biopsy of distant site is considered unwarranted by study investigator and treating 
physician then metastatic disease can be diagnosed by biopsy of primary tumor in 
combination with imaging studies (PET positive liver lesions for example). 
 
Biliary stent placement by PTC or ERCP to relieve obstructive jaundice (dilated biliary 
tree and a serum bilirubin level > normal or AST/ALT > 3x normal) is required prior to 
starting treatment on study.  
 ERCP or PTC is a procedure which allows the doctor to take detailed X-rays of the bile 
duct and/or pancreas and to relieve obstruction of the biliary tree. For this study metallic 
biliary stents may be used to drain the biliary tree and are preferred. If a stent becomes 
occluded, it shall be replaced with a metal stent unless there is a specific contra-
indication. 
 
Electrocardiogram (EKG)   
 
Research bloods: See section 12.0 
 
 
 

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Core Needle Biopsy of Tumor in Phase 2 Expansion Cohort 
 For Phase 2 expansion cohort, pre-treatment biopsies are required. The lesion to be 
biopsied must be accessible via percutaneous core needle. No endoscopic or laparoscopic 
biopsies are allowed. No lung lesions are allowed. Lesions that can be imaged by 
ultrasound are strongly preferred. If a lesion can be imaged by both ultrasound and CT 
scan, ultrasound is required unless there are special circumstances. Such cases must be 
discussed in advance with either the overall study PI or the medical monitor. Each biopsy 
must consist of four individual core needle biopsies. FNA is not acceptable. Details of 
biopsy handling are included in the lab manual. A paired on-treatment biopsy of the same 
lesion performed in the same fashion is also required during study week 8. Patients who 
cannot undergo a second biopsy for compelling medical reasons (determined by 
discussion between the treating physician, PI, and Sponsor) may stay on study. In the 
case of significant clinical response, if a previously biopsied lesion is no longer available, 
an alternate lesion may be biopsied but such a situation must be documented. 
 
9.2 
Evaluations during Treatment 
The following evaluations will be performed during the study: 
 
Day 1, 8 and 15 of each cycle: 
 
 Measurements of vital signs  
 Weight and determination of performance status to be completed on Day 1 of each cycle 
 CBC, differential, and platelets, serum chemistry tests (1 tablespoon of venous blood) 
including total bilirubin, AST, ALT, alkaline phosphatase, serum electrolytes (sodium, 
potassium, chloride, CO2), BUN, Cr, glucose, calcium. If patients are found to have ANC 
< 500, daily CBC will be performed until ANC > 500. 
 Review of concurrent medications 
 Adverse event evaluation   
 
Core Needle Biopsy during Study Week 8 (Prior to Start of Cycle 3) 
 
 A core needle biopsy of the same lesion performed in the same fashion as the pre-
treatment study biopsy must be performed 
 
Evaluations Following Completion of Cycle 2 (And Every 2 Cycles Thereafter) 
 
The following evaluations will be performed at the completion of every 2 cycles: 
 
 Serum CA 19-9 
 If a patient had a normal CA 19-9 at the beginning of the study but an abnormal CEA, 
then a CEA will be drawn instead and used to follow the patient. 
 Interval imaging study of the same modality used at beginning of study 

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 PET scan (done only once at the end of the first two cycles in up to 30 patients at selected 
institutions for research purposes ) 
 Study bloods: See section 12.0 
 
10.0 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The list of 
AEs (Section 7.1) and the characteristics of an observed AE (NCI Common Terminology 
Criteria for Adverse Events Version 4.03 (CTCAE 4.03)) will determine whether the event 
requires expedited reporting in addition to routine reporting. 
 
10.1 
Adverse Event Reporting 
Subject data accrued on this study will be reported in accordance with Code of Federal 
Regulations Title 21 (21CFR) 312.32. 
 
This study will utilize the descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03 for grading all adverse events. 
All appropriate treatment areas should have access to a copy of the CTCAE version 4.03. A copy 
of the CTCAE version 4.03 can be downloaded from the CTEP web site (http://ctep.cancer.gov).  
 
The P.I. will notify the IRB and NewLink Genetics (Study Sponsor) who in turn will notify the 
FDA and other regulatory agencies of all serious adverse events as required by law or regulation.  
All participating investigators will be notified of IND Safety Reports by Investigator Alerts sent 
through email. Serious Adverse Event (AE) Reporting by investigators will be done as outlined 
in Table 6. 
 
Definitions for reporting purposes:   
 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in 
severity during the course of the study.  Intercurrent illnesses or injuries should be regarded as 
adverse events.  Abnormal results of diagnostic procedures are considered to be adverse events if 
the abnormality: 
 results in study withdrawal 
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
 
Related to the use of the drug:  There is a reasonable possibility (more likely than not) that the 
experience may have been caused by the investigational drug.  
 
A serious adverse event is any AE that is:  
 fatal 

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 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 a congenital anomaly or birth defect 
 an important medical event 
 
Reporting Requirements for Serious Adverse Events (21CFRPart312) 
 
Investigators MUST immediately report to the sponsor ANY serious adverse events within 
24 hours of learning of the SAE, whether or not they are considered related to the 
investigational agent(s)/intervention (21CFR312.64)  
 
An adverse events is considered SERIOUS if it results in ANY of the following outcomes: 
1. Death 
2. A life-threatening adverse event 
3. An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization for > 24 hours 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
5. A congenital anomaly/birth defect 
6. Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. (FDA21CFR312.32; 
ICHE2A and ICHE6).  
 
SAE reporting timelines are defined as: 
o “24 Hour; 5 Calendar Days” – The SAE must initially be reported within 24 hours of 
learning of the SAE, followed by a complete SAE report within 5 calendar days of the 
initial 24 hour report.  
 
Serious adverse events that occur more than 30 days after the last administration of 
investigational agent/intervention and are considered related to the investigational drug require 
reporting on the same timelines as noted above. 
 
Deaths clearly due to progressive disease should NOT be reported expeditiously but rather 
should be reported via routine reporting (death report). 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise in 
this protocol.  Any condition responsible for surgery should be documented as an adverse event 
if the condition meets the criteria for and adverse event.  
 

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Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
adverse event in the following circumstances: 
 Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures 
for a preexisting condition.  Surgery should not be reported as an outcome of an adverse 
event if the purpose of the surgery was elective or diagnostic and the outcome was 
uneventful. 
 Hospitalization or prolonged hospitalization required to allow efficacy measurement for the 
study. 
 Hospitalization or prolonged hospitalization for therapy of the target disease of the study, 
unless it is a worsening or increase in frequency of hospital admissions as judged by the 
clinical investigator. 
 
SAE Reporting Form and Content:  For those events that meet the criteria for serious as listed 
above, please complete a Serious Adverse Event Reporting Form.  This form will be provided by 
NewLink Genetics.  Please send to NewLink Genetics within the time frames listed above.  
Please FAX to (515) 296-3556 or EMAIL to SAE_Reporting@linkp.com.  Please call (515) 
598-2935 with any reporting questions.  You may also contact and send this form to the CRA 
designated for your site. 
 
AEs known and expected for gemcitabine and / or nab-paclitaxel will be attributed to 
gemcitabine and / or nab-paclitaxel. AEs previously seen and expected for indoximod will 
be attributed to indoximod. AEs not known and expected from gemcitabine and / or nab-
paclitaxel and not seen in phase 1/2 indoximod studies will be considered regimen toxicities 
initially. Any grade 3 or higher regimen toxicity mandates a conference call within the next 
3 business day between investigators and sponsor to discuss attribution and response.  
 
10.2 
Routine Adverse Event Reporting  
All Adverse Events must be reported in routine study data submissions.  AEs reported through 
expedited SAE reports must also be reported in routine study data submissions (CRFs). 
 
10.3 
Reporting Requirements for Baseline Adverse Events 
A pertinent positive finding identified on baseline assessment is to be documented as a Baseline 
Adverse Event using CTCAE terminology and grade on the provided Baseline CRF.  An 
expedited AE report is not required if a patient is entered on to the study with a pre-existing 
condition (e.g., elevated laboratory value, diarrhea).  The baseline AE must be re-assessed 
throughout the trial and reported if it fulfills expedited AE reporting guidelines.  
1)  If the pre-existing condition worsens in severity, the investigator must reassess the event 
to determine if an expedited report is required.  
2)  If the AE resolved and then recurs, the investigator must re-assess the event to determine 
if an expedited report is required.  
3)  No modification in grading is to be made to account for abnormalities existing at 
baseline.  
 

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13.0 
STUDY CALENDAR 
 
Calendar Notes: 
A:  Nab-paclitaxel 125 mg/m2 IV 
B:  Gemcitabine 1000 mg/m2 IV 
C:  Indoximod PO - dose determined by escalation or phase 2 dose 
D:  CA19-9 or CEA to be performed at completion of every 2 cycles 
E:  PET Scan (at selected institutions only) to be completed at baseline and once at end of the first 2 cycles 
F:  
 
 
. 
G: Blood for future testing – Sample sent same day, on room air, overnight express to NewLink Genetics for 
banking.  Samples should not be shipped on Fridays or day before U.S. holidays. 
H: Archival tumor tissue is obtained if possible.  
I:   Drawn pre-drug administration and then every 2 months during treatment (see section 12.5) 
  
Pre Study 
Cycle 1 
Additional Cycles  
FUV 
D1 
D8
D15
D22
D1
D8
D15
D22
Nab-Paclitaxel 
  
A 
A 
A 
  
A 
A 
A 
  
  
Gemcitabine 
  
B 
B 
B 
  
B 
B 
B 
  
  
Indoximod 
  
C 
C 
C 
C 
C 
C 
C 
C 
  
Informed consent 
X 
  
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
Medical history 
X 
  
  
  
  
  
  
  
  
  
Concurrent meds 
X 
X------------------------------------------------X 
Physical exam 
X 
X 
  
  
  
X 
  
  
  
X 
Vital signs 
X 
X 
X 
X 
  
X 
X 
X 
  
X 
Height 
X 
  
  
  
  
  
  
  
  
  
Weight 
X 
X 
  
  
  
X 
  
  
  
X 
Performance status 
X 
X 
  
  
  
X 
  
  
  
X 
CBC w/diff, plts 
X 
X 
X 
X 
  
X 
X 
X 
  
X 
Serum chemistry 
X 
X 
X 
X 
  
X 
X 
X 
  
X 
CA19-9/CEA 
X 
  
  
  
  
  
  
D 
  
  
C-Reactive Protein 
  
X 
  
X 
  
X 
  
X 
  
  
PT, PTT, INR 
X 
  
  
  
  
  
  
  
  
  
Urinalysis 
X 
  
  
  
  
  
  
  
  
  
EKG  
X 
  
  
  
  
  
  
  
  
  
Adverse event 
evaluation 
X 
X-------------------------------------------------X 
Tumor measurements 
X 
Tumor measurements are completed at each 
radiologic evaluation.  
Radiologic evaluation 
(CT or MRI) 
X 
CT or MRI to be completed every 2 cycles  
PET Scan 
X 
  
  
  
  
  
  
E 
  
  
B-HCG 
X 
  
  
  
  
  
  
  
  
  
 
  
 
  
 
  
 
 
Blood for future testing 
  
G 
  
  
  
G 
  
  
  
  
Archival tumor tissue 
  
H 
  
  
  
  
  
  
  
  
Blood & PBMC 
  
I 
Every 2 months during active treatment 
Paired Core Needle Bx 
X 
  
  
  
  
End of Cycle 2 
 

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14.0 
MEASUREMENT OF EFFECT 
14.1 
Antitumor Effect 
For the purposes of this study, patients should be re-evaluated for response approximately every 
8 weeks during treatment.  
 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline 
(version 1.1).  Changes in the largest diameter (unidimensional measurement) of the tumor 
lesions are used in the RECIST criteria. 
 
Both RECIST criteria and immune criteria for response will be used to determine progression. 
Patients must meet definition of progression under both criteria to be considered as having 
progressed. 
 
14.1.1 
Definitions: 
Evaluable for toxicity.  All patients will be evaluable for toxicity from the time of their first 
treatment with indoximod. 
 
Evaluable for objective response.  Only those patients who have received at least one cycle of 
therapy, and have had their disease re-evaluated will be considered evaluable for response.  
These patients will have their response classified according to the definitions stated below.  
(Note:  Patients who exhibit objective disease progression prior to the end of cycle 1 will also be 
considered evaluable.) 
 
Evaluable Non-Target Disease Response.  Patients who have lesions present at baseline that are 
evaluable but do not meet the definitions of measurable disease, have received at least one cycle 
of therapy, and have had their disease re-evaluated will be considered evaluable for non-target 
disease.  The response assessment is based on the presence, absence, or unequivocal progression 
of the lesions.  
 
14.1.2 
Disease Parameters 
Measurable disease.  Measurable lesions are defined as those that can be accurately measured in 
at least one dimension (longest diameter to be recorded) as >20 mm by chest x-ray, as >10 mm 
with CT scan, or >10 mm with calipers by clinical exam.  All tumor measurements must be 
recorded in millimeters (or decimal fractions of centimeters). 
 
Malignant lymph nodes.  To be considered pathologically enlarged and measurable, a lymph 
node must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm).  At baseline and in follow-up, only the short axis will 
be measured and followed. 
 

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Non-measurable disease.  All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm or pathological lymph nodes with ≥ 10 to <15 mm short axis), are considered 
non-measurable disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial 
effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses 
(not followed by CT or MRI), are considered as non-measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts should not 
be considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability described above. However, if non-cystic lesions are 
present in the same patient, these are preferred for selection as target lesions. 
 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, should be identified as target lesions and recorded 
and measured at baseline.  Target lesions should be selected on the basis of their size (lesions 
with the longest diameter), be representative of all involved organs, but in addition should be 
those that lend themselves to reproducible repeated measurements.  It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be selected.  A 
sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters.  If lymph nodes are to be 
included in the sum, then only the short axis is added into the sum.  The baseline sum diameters 
will be used as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
 
Non-target lesions.  All other lesions (or sites of disease) including any measurable lesions over 
and above the 5 target lesions should be identified as non-target lesions and should also be 
recorded at baseline.  Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up.  
 
14.1.3 
Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment. 
 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  
 
Chest x-ray  Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung.  However, CT is preferable.  
 

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Conventional CT and MRI  This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less. CT scans have slice thickness greater 
than 5 mm, are not acceptable.  High quality MRI is also acceptable. 
 
Ultrasound  Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement.  Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next.  If new lesions are identified by ultrasound in the course of the study, confirmation by CT 
or MRI is advised.  If there is concern about radiation exposure at CT, MRI may be used instead 
of CT in selected instances. 
 
Endoscopy, Laparoscopy  Can be used to evaluate presence of metastatic disease and / or 
resectabilty prior to surgery when treating physicians believe procedure is clinically indicated. 
 
Tumor markers  Tumor markers alone cannot be used to assess response.  If markers are initially 
above the upper normal limit, they must normalize for a patient to be considered in complete 
clinical response. 
Ascites or effusions  The cytological confirmation of the neoplastic origin of any effusion or 
ascites that appears or worsens during treatment when the measurable tumor has met criteria for 
response or stable disease is mandatory to differentiate between response or stable disease (an 
effusion may be a side effect of the treatment) and progressive disease. 
 
FDG-PET  While FDG-PET response assessments need additional study, it is reasonable to 
incorporate the use of FDG-PET scanning to complement CT scanning in assessment of 
progression (particularly possible 'new' disease).  New lesions on the basis of FDG-PET imaging 
can be identified according to the following algorithm:  
a) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. 
b) No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD.  If the 
positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT  scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan).  If the positive FDG-PET at follow-up corresponds to a pre-existing site of 
disease on CT that is not progressing on the basis of the anatomic images, this is not PD. 
c) FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in 
cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring. 
d) A ‘positive’ FDG-PET scan lesion is defined as one which is FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image. 
 
PET-CT  At present, the low dose or attenuation correction CT portion of a combined PET-CT is 
not always of optimal diagnostic CT quality for use with RECIST measurements.  However, if 
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quality to a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT can be 
used for RECIST measurements and can be used interchangeably with conventional CT in 
accurately measuring cancer lesions over time.  Note, however, that the PET portion of the CT 
introduces additional data which may bias an investigator if it is not routinely or serially 
performed. 
 
The PET scan done for research purposes only at selected institutions will not be used to 
determine progression under RECIST criteria. 
 
14.2 
Response Criteria 
14.2.1 
Evaluation of Target Lesions 
Complete Response (CR): 
Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to 
<10 mm. 
 
Partial Response (PR): 
At least a 30% decrease in the sum of the diameters of target 
lesions, taking as reference the baseline sum diameters 
 
Progressive Disease (PD): 
At least a 20% increase in the sum of the diameters of target 
lesions, taking as reference the smallest sum on study (this 
includes the baseline sum if that is the smallest on study).  In 
addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm.  (Note:  the 
appearance of one or more new lesions is also considered 
progressions). 
 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum 
diameters while on study 
 
14.2.2 
Evaluation of Non-Target Lesions 
 
Complete Response (CR): 
Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size 
(<10 mm short axis) 
 
Note:  If tumor markers are initially above the upper normal limit, 
they must normalize for a patient to be considered in complete 
clinical response. 
 
Non-CR/Non-PD: 
Persistence of one or more non-target lesion(s) and/or maintenance 
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Progressive Disease (PD): 
Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions.  Unequivocal 
progression should not normally trump target lesion status.  It must 
be representative of overall disease status change, not a single 
lesion increase.     
 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances, and the progression status should be 
confirmed at a later time by the review panel (or Principal Investigator). 
 
14.2.3 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required 
CR 
CR 
No 
CR 
> 4 weeks Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
 
> 4 weeks Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not evaluated 
No 
PR 
SD 
Non-CR/Non-
PD/not evaluated 
No 
SD 
documented at least once > 4 weeks 
from baseline** 
PD 
Any 
Yes or 
No 
PD 
 
no prior SD, PR or CR 
Any 
PD*** 
Yes or 
No 
PD 
Any 
Any 
Yes 
PD 
**    Only for non-randomized trials with response as primary endpoint. 
***  In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration.”  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
 
 
 
 

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For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since 
SD is increasingly used as an endpoint for assessment of efficacy in some trials so to 
assign this category when no lesions can be measured is not advised 
 
14.2.4 
Duration of Response 
Duration of overall response:  The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented. 
 
 
Duration of stable disease:  Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements.  
 
14.3 
Overall Survival  
For all patients, OS will be calculated from the date of randomization to the time of death. 
Patients who are still alive prior to the data cutoff for final efficacy analysis, or who dropout 
prior to study end, will be censored at the day they were last known to be alive.     
 
14.4 
Progression-Free Survival 
For all patients, PFS will be calculated from the date of randomization to the time of CT scan 
documenting relapse (or other unambiguous indicator of disease development), or date of death, 
whichever occurs first.  Patients who have no documented relapse and are still alive prior to the 
data cutoff for final efficacy analysis, or who dropout prior to study end, will be censored at the 
date of the last radiological evidence documenting absence of relapse. 
 
14.5 
Immune-related Response Criteria 
Investigators have relied on Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate 
antitumor responses to chemotherapeutic agents.  However, the responses that are seen with 
immunotherapeutic agents may extend beyond those of cytotoxic agents and could include 
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response criteria (irRC) may better capture the response patterns observed with some 
immunotherapeutic agents. 
 
14.5.1 
Antitumor response based on total measurable tumor burden  
For the immune-related response criteria (irRC), only index and measurable new lesions are 
taken into account.  At the baseline tumor assessment, the sum of the products of the two largest 
perpendicular diameters (SPD) of all index lesions is calculated.  At each subsequent tumor 
assessment, the SPD of the index lesions and of new, measurable lesions are added together to 
provide the total tumor burden: 
 
Tumor Burden = SPDindex lesions + SPDnew, measurable lesions 
 
14.5.2 
Time-point response assessment using irRC  
Percentage changes in tumor burden per assessment time point describe the size and growth 
kinetics of both conventional and new, measurable lesions as they appear.  At each tumor 
assessment, the response inn index and new, measurable lesions is defined based on the change 
in tumor burden (after ruling our irPD).  Decreases in tumor burden must be assessed relative to 
baseline measurements (i.e., the SPD of all index lesions at screening).   
 
14.5.3 
Overall response using the irRC   
The overall response according to the irRC is derived from time-point response assessments 
(based on tumor burden) as follows: 
 
irCR: complete disappearance of all lesions (whether measureable or not, and no new lesions) 
confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first 
documented 
 
irPR: decrease in tumor burden > 50% relative to baseline confirmed by a consecutive 
assessment at least 4 weeks after first documentation  
 
irSD: not meeting criteria for irCR or irPR, in absence of irPD 
 
irPD: increase in tumor burden > 25% relative to nadir (minimum recorded tumor burden) 
confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first 
documented 
15.0 
DATA REPORTING / REGULATORY REQUIREMENTS 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 
(Adverse Events: List and Reporting Requirements). 

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15.1 
Regulatory Compliance/Good Clinical Practices   
This study will be conducted in accordance with the following regulations and guidelines, to 
include but not limited to:  
 Declaration of Helsinki (October 2000)  
 Current ICH Guideline for Good Clinical Practice  
 21 CFR 50: Protection of Human Subjects 
 21 CFR 54: Financial Disclosure by Clinical Investigators  
 21 CFR 56: Institutional Review Boards  
 21 CFR 312: Investigational New Drug Application 
 
Regulatory Documentation 
Prior to study start-up, investigators will submit the following documents to NewLink Genetics 
Corporation, as outlined in the Essential Documents Section 8.0 of the ICH Guidelines for Good 
Clinical Practice to include but not limited to:  
 Signed Confidentiality Agreement  
 Signed Clinical Trial Agreement  
 Up-to-date signed and dated Curriculum vitae and copies of medical licenses for 
Principal and sub/co-investigators to be submitted promptly  
 Financial Disclosure form for Principal and one sub/co-investigator with financial 
disclosure forms for all investigators to be submitted promptly  
 FDA Form 1572  
 IRB approval to conduct the study: IRB-approved informed consent form,   
 Name and address of the IRB with the statement that it is organized and operates 
according to GCP and the applicable laws and regulations  
 IRB membership roster  
 Local laboratory certifications, its name and address  
 Local laboratory normal ranges (a dated copy for tests to be performed during the study). 
 Financial agreement, if applicable.  
 Signed and dated Investigator Agreement page of the final protocol and amendments, 
where applicable. 
 
Institutional Review Board (IRB)   
This Trial will be undertaken only after full approval of the protocol and addenda has been 
obtained from a local IRB and a copy of this approval has been received by the sponsor.  The 
IRB must be informed of all subsequent protocol amendments issued by the sponsor.  Reports on 
and reviews of, the trial and its progress will be submitted to the IRB by the investigator at 
intervals set force in its guidelines. 
   
Informed Consent   
Each subject must give written consent and sign other locally required documents after the nature 
of the study has been fully explained. The informed consent form must be signed prior to 
performance of any study-related activity with the exception of baseline imaging (if already 
obtained within 30 days prior to starting study treatment) and baseline lab studies (if already 

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obtained within 14 days prior to starting study treatment). The informed consent form that is 
used must be approved both by the sponsor and by the reviewing IRB.  The Informed Consent 
should be in accordance of the Declaration of Helsinki, current International Conference on 
Harmonization (ICH) and Good Clinical Practices (GCP) guidelines. 
 
15.2 
Administrative Requirements 
Protocol modifications  
The investigator will not modify this protocol without obtaining permission from the sponsor.  
All protocol amendments must be issued by the sponsor, signed and dated by the investigator, 
and should not be implemented without prior IRB approval, except where necessary to eliminate 
immediate hazards to the patients or when the change(s) involves only logistical or 
administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s).   
 
In situations requiring a modification, the investigator or other physician in attendance will 
contact the medical monitor by fax or telephone (see Contact Information page).  This contact 
must be made prior to implementing any departure from protocol.  Contact with the sponsor must 
be made as soon as possible in order to outline an appropriate course of action.   
 
Record Retention  
In compliance with the ICH/GCP guidelines the investigator/institution will maintain all CRFs 
and all source documents that support the data collected from each patient, and all trial 
documents as specified in Essential documents for the Conduct of a Clinical Trial and as 
specified by the applicable regulatory requirement(s).   
 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.  Essential documents must be retained until at least two years after the last 
approval of a marketing application in an ICH region or at least two years have elapsed since the 
formal discontinuation of clinical development of the investigational product.   
 
These documents will be retained for a longer period if required by the applicable regulatory 
requirements or by an agreement with the sponsor.  It is the responsibility of the sponsor to 
inform the investigator/institution as to when these documents no longer need to be retained.   
 
Case Report Forms (CRF)   
CRFs are provided for each patient.  Data must be entered onto CRFs in English.  All forms must 
be filled out in black ball-point pen.  CRFs must be signed by the investigator where indicated. 
  
All CRF corrections are to be made by the investigator or other authorized study center 
personnel as instructed on the CRF title page.  The investigator must authorize changes to the 
recorded safety and efficacy data.  
 
The Case Report Forms (CRF) will be designed for the capture of all relevant clinical data for 
this study.  The CRFs are to be completed as soon as possible after the subject’s visit, so that 
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data will be reviewed and authorized by the Investigator.  Copies of CRF data will be retained by 
the site and Sponsor in accordance with FDA regulations.   
 
Monitoring   
All clinical and standard laboratory data specified in this study will be collected and recorded by 
the nurse coordinator under the supervisions of the Principal Investigator and physician co-
investigator 
 
NewLink Genetics (sponsor) will perform on-site monitoring visits as outlined in the Monitoring 
Plan for this clinical trial. The dates of the visits will be recorded by the monitor in a trial center 
monitor visit log to be kept at the site. The first routine monitoring visit will usually be made 
approximately 4 weeks after enrollment has begun at that site. At these visits the monitor will 
verify the data entered onto the CRFs with the hospital or clinic records (source documents).  
  
At a minimum, source documentation must be available to substantiate patient eligibility and 
participation, proper informed consent procedures, adherence to protocol procedures, record of 
safety and efficacy parameters, adequate reporting and follow-up of adverse events, 
administration of concomitant medication, drug receipt/dispensing/return records, study 
medication administration information, and date of completion and reason.   
 
Specific items required as source documents will be reviewed with the investigator prior to the 
study. Findings from this review of CRFs and source documents will be outlined in a Site Visit 
Report and discussed with the investigator. The sponsor expects that, during monitoring visits, 
the investigator (and as appropriate the study coordinator) will be available, the source 
documents will be available, and a suitable environment will be provided for review of study-
related documents.   
 
Data Monitoring Committee 
This study will use a Data Monitoring Committee (DMC). The DMC will review accrual 
information, and safety data such as listing and nature of adverse events.  An independent 
statistician will provide the DMC with, safety data listing, data summary and appropriate 
analysis for review at the completion of the phase I study. The DMC will review the safety of the 
combination on a quarterly basis while any subject is still receiving study drug.  
 
Use of Information and Publication   
All information on indoximod, NewLink operations, patent application, manufacturing process 
and basic scientific data supplied by the sponsor to the investigator and not previously published 
is considered confidential and remains the sole property of NewLink Genetics and the PI. The 
investigator agrees to use this information only to accomplish this study and will not use it for 
other purposes without the sponsor’s written consent.  The investigator understands that the 
information developed in the clinical study will be used by NewLink in connection with the 
continued development of indoximod and thus may be disclosed as required to other clinical 
investigators or government regulatory agencies. To permit the information derived from the 
clinical studies to be used, the investigator is obligated to provide the sponsor with all data 
obtained in the study.   

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Any publication or other public presentation of results from this study requires prior review of 
NewLink Genetics. Draft abstracts, manuscripts and materials for presentation at scientific 
meetings should be provided to the sponsor as outlined in the clinical trial agreement. 
 
15.3 
Human Subjects Protection 
Rationale for subject selection  
Advanced pancreatic cancer affects men and women from all racial/ethnic groups. Patients from 
all racial/ethnic groups are eligible for this study if they meet the eligibility criteria.  We will 
make an attempt at enrolling representative proportions of minorities on this study.   
 
Efforts will be made to extend accrual to a representative population, but in this phase 1/2 study, 
a balance must be struck between subject safety considerations and limitations on the number of 
individuals exposed to potentially toxic and/or ineffective treatments on the one hand and the 
need to explore gender and ethnic aspects of clinical research on the other hand.  
 
Participation of Children 
No children will participate in this study. 
 
Evaluation of Benefits and Risks 
Advanced pancreatic cancer has a very poor overall prognosis. After failing currently available 
regimens, the chance of cure is rare if at all. The benefits of this approach are theoretical and it is 
hoped that the inhibition of IDO will lead to an effective anti-tumor immune response. By 
generating an immune response against the subject's tumor, their overall survival might be 
improved. 
 
Given the safety demonstrated by indoximod in several clinical studies, and the poor prognosis 
of this patient population, it is believed that the possible benefits from improved survival 
probability far outweigh the risk to the patient.  The information obtained in this study may be 
extremely valuable in the treatment of malignancies in the future. The chance of this 
experimental treatment to provide clinical benefit is unknown.  All possible benefits and risks 
will be carefully explained to all patients and the Informed Consent Document will be signed by 
the subject prior to entrance into the protocol. 
 
There are no new anticipated severe adverse side effects to the treatment approach technique 
employed in this study. Theoretical risks may include the induction of unanticipated autoimmune 
disease and/or liver, kidney, lung, heart and CNS damage and/or coagulopathy and bleeding as a 
result of excessive activation of the complement system.  Expected risks and discomforts to the 
patients are minimal and will be those of needle sticks for phlebotomy. Patients will be treated as 
deemed medically appropriate for any immediate or delayed adverse event related to the 
treatment. 
 
Blood and tissue specimens collected in the course of this research project may be banked and 
used in the future to investigate new scientific questions related to this study.   

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Consent Processes and Documents 
All patients will be thoroughly screened prior to admission onto this study.  During this time, the 
subject, along with family members, will be presented with a detailed description of the protocol 
treatment.  The specific requirements, objectives, advantages and disadvantages will be 
presented.  The Informed Consent document is given to the subject and they are asked to review 
it and ask questions prior to agreeing to participate in this protocol.  The subject will be reassured 
that participation on this trial is entirely voluntary and that they can withdraw or decide against 
treatment at any time without adverse consequences.  The Principal Investigator or their designee 
is responsible for completing the consent process and a copy of the completed Consent 
Document is offered to the subject. 
 
Recruitment Strategy 
Patients, their physicians or family members may contact the clinical sites directly.  Information 
about the clinical trial can be obtained at clinicaltrials.gov. Given the number of patients with 
metastatic pancreas cancer and the limited therapy available, we believe enrollment for this trial 
will be completed in less than 2 years.  
 
Patient Confidentiality 
Strict patient confidentiality is standard policy at clinical research sites.  Standard practices will 
be followed. 
 
16.0 
STATISTICAL METHODS  
16.1.1 General Considerations 
Descriptive statistical methods will be used to summarize data from this study. Unless stated 
otherwise, the term descriptive statistics refers to number of patients (n), mean, median, standard 
deviation (SD), minimum and maximum for continuous data and frequencies and percentages for 
categorical data. 
 
A formal detailed statistical analysis plan (SAP) will be created prior to the review of any data. 
All data collected during the study will be included in data listings. Unless otherwise noted, the 
data will be sorted first by dose level, patient number, and then by date within each patient 
number.  
 
All statistical analyses will be conducted with the SAS® software package version 9.2 or higher. 
16.1.2 Determination of Sample Size 
Phase 1 component: The Phase 1 component of the trial will be conducted to assess the safety of 
indoximod and to identify the RLT and RP2D of indoximod in combination with gemcitabine 
plus nab-paclitaxel in patients with metastatic pancreas cancer.  
 
No formal sample-size estimation was performed and no formal statistical hypothesis testing will 
be performed during this phase. The selection of sample size was based on a standard 3 + 3 

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design that is commonly used in Phase 1 trials of anti-cancer investigational drugs. For the dose 
escalation portion of the study, the maximum sample size will be 18 patients if 6 patients are 
assigned at 3 dose levels. 
 
Phase 2 component: The primary objective of the Phase 2 component is to assess the efficacy of 
indoximod in combination with gemcitabine plus nab-paclitaxel as determined by overall 
survival (OS) in patients with metastatic adenocarcinoma of the pancreas.  
 
Assuming an expected median OS of 8.5 months for patients treated with gemcitabine plus nab-
paclitaxel based on historical data [11], approximately 56 OS events would be required to detect 
with 80% power and one-sided significance level of 0.05 an increase in median OS of 30% 
(12.14 months). A total of 80 patients will be enrolled to account for up to 30% of patients being 
non-evaluable or lost to follow-up. No patients from Phase 1 will roll over into Phase 2.  
 
Phase 2 biopsy cohort: The endpoint of the biopsy cohort is to obtain pre- and post-treatment 
tumor biopsies that can be analyzed retrospectively upon completion of the trial to gain insight 
into the scientific basis for any observed treatment effect and possibly guide future trial design 
and patient selection. As this is an exploratory effort, no formal sample-size estimation can be 
performed. According to general guidelines regarding the sample size for pilot or translational 
studies, a sample size of up to 40 patients would provide a reasonable precision for the 
estimation of pilot information. 
 
The PASS 12 package was used for the Phase 2 component sample size estimation (NCSS, LLC. 
Kaysville, UT)[12]. 
 
16.2 
Analysis Populations 
16.2.1 Phase 1 Component Analysis Populations 
 
There will be 1 analysis population defined for the Phase 1 component, the safety population.  
 
The Safety Population will consist of all patients receiving at least 1 dose of indoximod.   
 
16.2.2 Phase 2 Component Analysis Populations 
 
There will be 3 analysis populations defined for the Phase 2 component, 1 safety population and 
2 efficacy evaluation populations   
 
The Safety Population will consist of all patients receiving at least 1 dose of indoximod. This 
includes both the Phase 2 cohort and the biopsy expansion cohort. 
 
The Efficacy Evaluable (EE) Population will consist of all patients who have received at least 
one cycle of therapy and have had their disease re-evaluated through radiographic imaging and 
assessed according to RECIST version 1.1.  EE will also include any patients who exhibit 

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objective disease progression by radiographic imaging assessment according to RECIST version 
1.1 prior to the end of cycle 1.  
 
The Evaluable for Non-Target Disease Response (ENDR) Population will include patients who 
have lesions present at baseline that are evaluable but do not meet the definitions of measurable 
disease, have received at least 1 cycle of therapy, and have had their disease re-evaluated through 
radiographic imaging.  The response assessment is based on the presence, absence, or 
unequivocal progression of the lesions.  
 
16.3 
Primary and Secondary Endpoints 
16.3.1 Phase 1 Component Primary Endpoints 
The primary endpoints of the Phase 1 component are to characterize the RLTs and to determine 
the RP2D of indoximod when administered with a standard of care chemotherapy backbone 
consisting of gemcitabine plus nab-paclitaxel.  
 
An RLT is defined in Section 4.2.1 as only grade 3 and 4 toxicities that are attributable to the test 
agent and result in the delay of the administration of the backbone chemotherapy, gemcitabine 
plus nab-paclitaxel. The RP2D will be determined by the identified MTD, the highest dose at 
which ≤ 1 out of 6 patients experiences an RLT, and include an assessment of toxicities that 
occur at later time points. Dose Escalation Rules are defined in Section 4.2.2.  
 
Analysis of Phase 1 component primary endpoints will be performed on the Safety Population. 
 
16.3.2 Phase 2 Component Primary Efficacy Endpoint 
The primary efficacy endpoint for the Phase 2 component is Overall Survival (OS).  For all 
patients, OS will be calculated from the date of enrollment to the time of death. Patients who are 
still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, 
will be censored at the day they were last known to be alive.  
Kaplan-Meier methods will be used for estimation of summary statistics.  
 
Analysis of Phase 2 component primary endpoints will be performed on the EE Population. 
 
 
16.3.3 Phase 2 Component Secondary Endpoints 
Secondary endpoints for the Phase 2 component include: 
 Progression Free Survival (PFS) 
 
 

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 To determine the response rate, duration of response, and duration of overall CR of 
patients treated with gemcitabine and nab-paclitaxel with indoximod. 
 To determine the time to progression of patients treated with gemcitabine and nab-
paclitaxel with indoximod. 
For all patients, PFS will be calculated from the date of enrollment to the time of CT scan 
documenting progression (or other unambiguous indicator of disease development), or date of 
death, whichever occurs first.  Patients who have no documented progression and are still alive 
prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, will be 
censored at the date of the last radiological evidence documenting absence of progression.  
 
Response and disease progression will be evaluated using RECIST version 1.1, and measurement 
of effect is further defined in Section 14. Response rate is defined as the percentage of patients 
with either complete or partial response while on study. Time to progression will be calculated 
from the start of treatment to the time of documented radiological evidence of disease recurrence 
or progression.  
 
The duration of overall response is measured from the time measurement criteria are met for CR 
or PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented. The duration of overall CR is measured from the time measurement 
criteria are first met for CR until the first date that progressive disease is objectively documented. 
Stable disease is measured from the start of the treatment until the criteria for progression are 
met.  
 
Analysis of Phase 2 component secondary endpoints will be performed on the EE Population.  
Additional exploratory analyses may be performed. 
 
16.4 
Safety Analysis 
Additional safety analyses will be conducted using the Safety Population and will include 
summaries of adverse events (AEs), concomitant medications, vital signs, hematology and 
chemistry laboratory parameters, and 12-lead electrocardiogram, which will be described further 
in the Statistical Analysis Plan. 
 
Adverse Events will be graded using CTCAE version 4 and coded using the Medical Dictionary 
for Regulatory Activities (MedDRA®) for purposes of summarization. All AEs occurring during 
the study will be included in by-patient data listings and tabulated. Events leading to death, 
SAEs, and events resulting in study discontinuation will be tabulated. Safety variables will be 
tabulated and presented by dose cohort. Exposure to study drug and reasons for discontinuation 
of study treatment will be tabulated. 
 
Medical History will be coded using MedDRA, and will be included in by-patient data listings 
and tabulated. Concomitant medications will be coded using the World Health Organization 

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(WHO) Drug Dictionary. The use of concomitant medications will be included in by-patient data 
listings and tabulated. 
 
17.0 
REFERENCES 
 
1. 
Beatty, G.L., et al., CD40 Agonists Alter Tumor Stroma and Show Efficacy Against 
Pancreatic Carcinoma in Mice and Humans. Science, 2011. 331(6024): p. 1612-1616. 
2. 
Kraman, M., et al., Suppression of Antitumor Immunity by Stromal Cells Expressing 
Fibroblast Activation Protein–α. Science, 2010. 330(6005): p. 827-830. 
3. 
Morse, M.A., J.R. Hall, and J.M. Plate, Countering tumor-induced immunosuppression 
during immunotherapy for pancreatic cancer. Expert Opinion on Biological Therapy, 
2009. 9(3): p. 331-339. 
4. 
Sarkhosh, K., et al., Temperature-sensitive polymer-conjugated IFN-gamma induces the 
expression of IDO mRNA and activity by fibroblasts populated in collagen gel (FPCG). J 
Cell Physiol, 2004. 201(1): p. 146-54. 
5. 
Qian, F., et al., Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in 
reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human 
epithelial ovarian cancer. Cancer Res, 2009. 69(13): p. 5498-504. 
6. 
Potula, R., et al., Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination 
of virus-infected macrophages in an animal model of HIV-1 encephalitis. Blood, 2005. 
106(7): p. 2382-90. 
7. 
Muller, A.J., et al., Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory 
target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med, 
2005. 11(3): p. 312-9. 
8. 
Metz, R., et al., Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical 
target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-
tryptophan. Cancer Res, 2007. 67(15): p. 7082-7. 
9. 
Conroy, T., et al., GEMCITABINE PLUS NAB-PACLITAXEL versus gemcitabine for 
metastatic pancreatic cancer. N Engl J Med, 1817. 364(19): p. 1817-25. 
10. 
Horton, T.M., et al., Toxicity assessment of molecularly targeted drugs incorporated into 
multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): 
review from an international consensus conference. Pediatr Blood Cancer. 54(7): p. 872-
8. 
11. 
Von Hoff, D.D., Randomized phase III study of weekly nab-paclitaxel plus gemcitabine 
versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas 
(MPACT). 2013 Gastrointestinal Cancers Symposium Abstract LBA148.  
12. 
Hintze, J. (2013). PASS 12. NCSS, LLC. Kaysville, Utah, USA. www.ncss.com. 
 
 
 
 
 
 

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18.0 
APPENDICES 
18.1 
Appendix A: Performance Status Criteria 
 
 
ECOG Performance Status Scale 
 
 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, able 
to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no evidence 
of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease. 
1 
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 

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18.2 
Appendix B. Study Medication Diary 
Study Medication Diary                Subject Initials: ___ ___     Subject #: NLG2104 - ___ ___ ___ 
Cycle: _____      Cycle Start Date: __ __ / __ __ __ / __ __ __ __   Subjects planned daily dose: _________ mg 
# of capsules dispensed: ____ by: _____________________________________ on __ __ / __ __ __ / __ __ __ __ 
# of capsules returned:    ____ to:  ____________________________________ on __ __ / __ __ __ / __ __ __ __ 
INSTRUCTIONS TO THE PATIENT: 
1.      Complete one form for each Cycle.   
2.      You will take ____ capsules each day.  Take the capsules with water. Do not eat or drink anything other than water for 1 
hour before or after taking the study medication. (Do not take with antacids). 
3.      Record the date, the number of capsules you took, and when you took them.   
4.      If you have any comments or notice any side effects, please record them in the Comments column. 
5.      Please bring your pill bottle and this form to your physician at each return visit.
Date 
Day 
#Capsules  
 AM Dose   
(time HH:MM) 
#Capsules   
 AM Dose     
(time HH:MM)
Comments 
Subject Initials (Initialed by Subject): ___ ___ 
Date:          /               / _ __ __ __       
To be completed by site staff upon return of study medication diary: 
 
Total Number of Capsules taken this cycle:    
  Percent of Compliance: __________________ 
 
Comments on capsules taken, capsules not taken as planned, capsules lost, or other discrepancies:   
 
  
Signature of Study Nurse or Study Designee: 
Date:          /               /  
 
 
 
 

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18.3 
Appendix C: Informed Consent Form Template 
RESEARCH PATIENT INFORMATION AND CONSENT FORM 
 
TITLE:  
A Phase 1/2 Study of Indoximod in Combination with Gemcitabine and Nab-Paclitaxel in 
Patients with Metastatic Adenocarcinoma of the Pancreas  
 
Federal regulations require written informed consent from subjects before participation in a 
research study so that they can know the nature and risks of participation and decide to participate 
or not to participate in a free and informed manner.  You are asked to read this consent form 
describing the research study and how you will participate in it if you consent to do so.  Signing 
this consent form will indicate that you have been informed and that you give your consent. 
 
Participation 
 
You are being asked to consider participation in a research study. Your participation in this study 
is entirely voluntary. It is up to you to decide whether to take part or not. Even if you do decide to 
take part, you are free to partially or completely end your participation in the study. 
 
Your eligibility to participate in this study will be decided based on the screening procedures 
described below and other eligibility criteria. Before you can take part in this study, it is important 
that you understand what this study involves. Please read this information carefully and ask any 
questions that you might have. 
 
You are being asked to take part in this research study because you have been diagnosed with 
metastatic pancreatic cancer. 
 
Why is this research being done? 
 
The purpose of this study is to determine the effects, good and/or bad, of the chemotherapy regimen 
gemcitabine and nab-paclitaxel with the addition of indoximod (an experimental drug) to find out 
if the combination is possibly better than the gemcitabine and nab-paclitaxel regimen alone.  
 
About the study drugs:  
 
Indoximod treatment is experimental at this time whereas gemcitabine and nab-paclitaxel are 
intravenous drugs that are approved for commercial use as a prescribed drug by the US Food and 
Drug Administration (US FDA) for the treatment of metastatic pancreatic cancer.  
 
The experimental drug indoximod is an oral medication that blocks an enzyme called IDO. Doctors 
think that tumors use IDO to escape attack by your body’s immune system, so by blocking this 
IDO enzyme it may help your body attack the tumor cells more effectively. Indoximod given along 
with standard chemotherapy may increase the effectiveness of the chemotherapy regimen 
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Should you take part in this study? 
 
This form tells you about this research study. After reading through this form and having the 
research explained to you by someone conducting this research, you can decide if you want to take 
part in it. 
 
 You may have questions this form does not answer. If you have questions, feel free to ask 
the study doctor or the person explaining the study, as you go along. You do not have to 
guess at things you do not understand. Ask the people doing the study to explain things in 
a way you can understand. 
 Take your time to think about the information that has been provided to you. 
 Have a friend or family member go over the form with you. 
 Talk it over with your regular doctor 
 
It is up to you. If you choose to be in the study, then you should sign the form. If you do not 
want to take part in this study, you should not sign the form.  
 
Why are you being asked to take part? 
 
We are asking you to take part in this research study because you have metastatic pancreatic cancer 
(pancreatic cancer that has spread to other parts of your body). 
 
How many people will participate in the study? 
 
This study will have two parts, a dose-escalation phase (the first part of the study) and then later, 
a dose-expansion part (the second part of the study). In the first part of the study, up to 18 people 
will be asked to participate. In the second part, 80 additional people will be asked to participate 
across multiple institutions.  After the second part has been fully enrolled, an additional 40 subjects 
will be asked to participate in an expansion study.  Approximately <<XX>> patients will be 
enrolled at <<CLINICAL SITE>>>. 
 
What will happen during this study? 
 
Screening 
The screening period is held within 14 days before starting the study treatment to find out if you 
can be in the study. During this period, you will need to come to the clinic or study site for multiple 
tests.  More than one screening visit may be required.  If these tests show that you can be in the 
study and you choose to take part, then you will be entered in the study. The following screening 
examinations, tests, or procedures will be performed after you have given consent to participate in 
this study: 
 
 Medical history, including information about you and your cancer, previous treatments for 
your cancer and other medications you are taking or have taken.  Certain medications are 
not allowed to be taken during the study treatment. 

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How long will you be asked to stay in the study? 
 
It is unknown exactly how long you would stay on the study. You will receive the chemotherapy 
every 3 weeks with a week of rest (cycle).  The indoximod treatment is given daily throughout the 
cycle.  Treatment would continue until your disease stops responding to the treatment or you can 
no longer tolerate the study therapy. You are also free to stop participating at any time you decide 
to do so. 
 
What other choices do you have if you do not participate? 
 
If you decide you do not want to take part in this study that is okay. If you decide not to participate 
in this research, you have other choices. These choices include other clinical trials, conventional 
chemotherapy agents, or best supportive care to ease any symptoms you have without treating the 
underlying cancer. 
 
When will you be taken off study? 
 
You may be removed from the study for any of the following reasons: 
 If your disease progresses 
 If you do not adhere to the protocol treatment plan 
 If you request to withdraw from the study or refuse further therapy 
 Unacceptable side effects. You may be removed from the study for any complication of 
treatment that the investigator feels is life threatening. 
 If you do not meet eligibility criteria 
 
Will you be paid for taking part in this study? 
 
We will not pay you for the time you volunteer while being in this study. 
 
What will it cost you to take part in this study? 
 
You and/or your insurance company will be financially responsible for your hospital inpatient, 
outpatient and follow-up visits that would normally or routinely occur in the management of your 
disease. Inpatient and outpatient visits could include charges for treatments, medications, 
physician visits, laboratory tests and procedures. You and/or your insurance company will be 
responsible for paying for the charges, which are considered routine, since you would have 
received these services even if you were not participating in this study 
 
You will be responsible for any costs not covered by your insurance company, including 
deductibles, co-payments and all out-of-pocket expenses. 
 
You and/or your insurance company will not be responsible for paying for testing and procedures 
that are specifically required for this research study and are not considered being part of the routine 
management of your disease, if these procedures are performed at <<<CLINICAL SITE>>>. 

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Additionally, you and/or your insurance company will not be responsible for special blood tests to 
measure the drug levels. 
 
<<<ADD SPECIFIC RESEARCH TESTS HERE>>> 
 
NewLink Genetics will supply indoximod at no charge while you take part in this study.  
 
Even though it probably won’t happen, it is possible that the manufacturer may not continue to 
provide the indoximod to <<<CLINICAL SITE>>> for some reason. If this would occur, other 
possible options are: 
 
 You might be able to get the indoximod from the manufacturer or your pharmacy, but you 
or your insurance company may have to pay for it. 
 
 If there is no indoximod available at all, no one will be able to get more and the study 
would close. 
 
If a problem with getting indoximod occurs, you study doctor will talk to you about these options. 
 
What are the potential benefits if you take part in this study? 
 
We do not know if you will get any health benefits by taking part in this study. We do not know if 
the experimental treatment will help you. That is why we are doing this study. We hope that what 
we may learn can benefit others in the future. 
 
What are the risks if you take part in this study? 
 
INDOXIMOD 
The following may be related risks and side effects of the indoximod therapy that have been 
observed in patients that have received it: 
 
Most Common Side Effects:  (Likely to happen to 20% or more of patients) 
 Nausea 
 Fatigue or feeling tired 
 
Common Side Effects: (Likely to happen to 10 – 19% of patients) 
 Anorexia or loss or appetite 
 Decrease in red blood cells (anemia) 
 Diarrhea 
 Vomiting 
 
Less Common Side Effects: (Likely to happen to 5 to 10% of patients) 
 Decrease in white blood cells (neutrophils and lymphocytes) 
 Headache 

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 Rash 
 Constipation 
 Hair loss 
 
Rare Side Effects: (Likely to happen to less than 5%) 
 Dizziness 
 Lung Infection 
 Fever associated with low white blood cells (febrile neutropenia) 
 Increase in blood potassium, glucose, and creatinine levels  
 Multi-organ failure 
 Sleeplessness (insomnia) 
 Mouth sores (oral mucositis) 
 Dehydration 
 Ringing in ears, hearing loss 
 Low blood levels of sodium 
 Low blood pressure (hypotension) 
 Redness, pain, numbness, and possible peeling of hands and feet 
 Respiratory failure 
 Inflammation of the colon (colitis) 
 Inflammation of the joints (arthritis) 
 Decrease in platelets 
 Muscle weakness 
 Inflammation of the liver (hepatitis) 
 Soft tissue infections 
 Increased bilirubin level in blood 
 Low blood levels of glucose, phosphate, calcium, magnesium, and albumin 
 Peripheral sensory neuropathy 
 Shortness of breath 
 Abdominal pain 
 Itching skin 
 Blurred vision 
 Altered taste 
 Inflammation of the inner lining of the lungs (pneumonitis) 
 Accumulation of fluid in the abdomen (ascites) 
 Increase in white blood cells 
 Parkinsonism (tremor, rigidity, instability, slowness of movement, masked face, voice 
changes) 
 
Autoimmune Events 
Autoimmunity is a term that describes when your immune system begins to attack normal cells in 
your body. Two patients out of 48 in a completed indoximod study developed an autoimmune 
reaction in their pituitary gland called hypophysitis. Both of these patients received prior 

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experimental immune therapies which may have increased the risk of this occurring, but there is a 
distinct possibility that this may occur with indoximod alone.  
One of the two hypophysitis patients were on low dose steroids and thyroid hormone as long as 
they were alive, and one of the patients was able to stop the steroids but remained on thyroid 
hormone for the rest of her life. To date, none of the patients who did not receive prior immune 
therapies have developed this side effect. The pituitary gland is considered the “master gland” 
which coordinates the function of your other glands such as your thyroid, adrenals, and gonads 
(ovaries/testicles). If it does not function properly (pituitary insufficiency) you may experience 
symptoms of  
 Weakness  
 Fatigue  
 Loss of libido (lack of interest in sexual intercourse) 
 You may need to take hormone replacement therapy to treat these or other symptoms.  
 
Another hormone called ACTH (a hormone secreted by the pituitary gland), excites the adrenal 
gland (a gland situated above the kidneys) to make steroids, particularly cortisol. If there is a 
decline in ACTH (ACTH deficiency) you may experience  
 Weight loss  
 Lack of appetite (anorexia)  
 Weakness  
 Nausea  
 Vomiting  
 Low blood pressure (hypotension).  
 
Stopping the study drug and using steroids to calm the immune system are effective in many cases 
of autoimmune disease, but there is a risk of chronic autoimmune disease requiring treatment for 
longer periods of time. We will monitor you closely for any signs of autoimmune conditions and 
treat you for them if necessary. Prior experience with other immunotherapy agents seems to 
indicate those who do develop these autoimmune events may have a higher likelihood of their 
cancers responding to treatment, but it is not known if this is the case with indoximod.  
 
GEMCITABINE (Gemzar®) 
 
The following side effects are common (occurring in more than 30%) for patients taking 
gemcitabine: 
 Flu-like symptoms (muscle pain, fever, headache, chills, fatigue) 
 Fever (within 6-12 hours of first dose) 
 Fatigue 
 Nausea (mild) 
 Vomiting 
 Poor appetite 
 Skin rash 
 Low Blood Counts (your white and red blood cells and platelets may temporarily decrease.  
This can put you at increased risk for infection, anemia and/or bleeding.) 

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 Temporary increases in liver enzymes 
 Blood or protein in the urine 
These are less common side effects (occurring in 10 -29% of patients): 
 Diarrhea 
 Weakness 
 Hair loss 
 Mouth sores 
 Difficulty sleeping 
 Shortness of breath 
 
There can be treatment delays or interruptions, if needed, to make the treatment safer or more 
tolerable if there are side effects. 
 
NAB-PACLITAXEL (Abraxane®) 
 
The following side effects are Common (occurring in more than 30%) for patients taking nab-
paclitaxel: 
 Low Blood Counts (Your white and red blood cells and platelets may temporarily decrease.  
This can put you at increased risk for infection, anemia and/or bleeding.) 
 Hair loss 
 Numbness, tingling, pain, or weakness in the hands or feet 
 Tiredness 
 Rash 
 Nausea and vomiting 
 Diarrhea 
 Swelling in the hands or feet 
 Fever 
 Decreased appetite 
 
Less Common (occurring in 20 -29% of patients): 
 Dehydration 
 
Uncommon (occurring in 10 to 19% of people) 
 Muscle pain 
 Joint pain 
 Weakness 
 Mouth sores and mouth pain 
 Alteration in taste 
 Headache 
 Decrease in blood potassium levels 
 Cough 
 Nose bleeds 
 Urinary Tract Infections 
 Pain in arms or legs 

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 Depression 
 
Rare but could be Serious (occurring in less than 10%) 
 Infection 
 Pneumonitis (inflammation of lung tissues) 
 Hypersensitivity reactions including anaphylactic reactions (allergic reactions that are life 
threatening) 
 Abnormal heart beat 
 High blood pressure 
 
Is there any risk to your unborn children if you take part in this study? 
 
For Women: 
If you are pregnant, you may not participate in this study, because there may be risks to you and 
your unborn baby. Breastfeeding (nursing) mothers will not be included in this study, since it is 
not known whether the drugs in this study will be passed on to the baby in the mother’s milk. If 
you are currently breastfeeding and wish to continue, your study doctor may recommend another 
treatment. 
 
If you are a female of childbearing potential (able to become pregnant), you will be given a 
pregnancy test at no cost to you before beginning any study treatment. 
 
Tell one of the study doctors right away if: 
 You are pregnant 
 You get pregnant 
 You are breastfeeding 
 
If you are a man: 
We do not know what the experimental drug will do to your sperm. Should you get a woman 
pregnant, there could be harm to the unborn baby. You and your partner should use at least one 
effective birth control method (two are preferable when possible) if you are having sexual 
intercourse with a woman of childbearing potential. 
 
For men and women: 
Whether you are a man or a woman, there may be risks to your unborn children. If you take part 
in this study, you must use at least one effective birth control method (two are preferable when 
possible) as discussed with your study doctor. Examples of birth control methods include: 
 Oral birth control pills 
 Birth control patch 
 Implanted (injectable contraceptive hormones or mechanical products such as intrauterine 
device) 
 Barrier methods (diaphragm, condoms, spermicidal) 
 Tubal ligation or vasectomy 
 Abstinence 

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Certain birth control methods may not be a good choice for you (for example some patients with 
breast cancer should not use birth control methods that contain hormones). You should discuss the 
method of birth control which is best for you to use both during study treatment and for a period 
of time after treatment. Also, if you are a sexually active premenopausal woman or man the study 
staff will review your birth control use at each study visit. Use of contraception or abstinence 
should continue for a minimum of 1 month after completion of the study.   
 
Please place your initials in the appropriate box below: 
 
 
I am surgically sterile (hysterectomy, tubal ligation or vasectomy) or have gone through 
menopause (no period for 24 consecutive months). 
 
 
I understand and agree to use contraception during treatment and for the time recommended 
by my doctor after treatment is over. 
 
 
Whether you are a woman or a man, you should tell your doctor immediately if you become 
pregnant or if your partner becomes pregnant. The long-term effects of the study treatment on 
fertility are unknown. This means that it is unknown if treatment with these medication will affect 
your ability to have children in the future. 
 
What if you get sick or hurt while you are in the study? 
 
If you become ill or are hurt while you are in the study, get the medical care that you need right 
away. 
 
Research-Related Injury 
 
Your safety is the major concern of every member of the research team.  If you experience physical 
injury or illness as a result of participating in this research study, the sponsor will reimburse you 
for reasonable and necessary medical expenses when the injury is found to be the result of the 
study drug used as indicated in the research plan and is not the result of negligence or misconduct 
of any agent or employee of <<clinical site>>. Financial compensation for lost wages or other non-
medical costs will not be provided. Agreeing to participate in this study and signing this document 
does not waive your rights in the event of negligence on the part of the Hospital or research staff. 
 
Further information about research-related injuries is available by contacting the <<clinical site>> 
Institutional Review Board at (XXX) XXX-XXXX. 
 
Further information concerning policies in this regard, or information about the conduct of this 
study or rights of research subjects, may be obtained from the principal investigator. 
 
Confidentiality, Collection and Use of Study Data 

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Your study doctor will collect information about you, on your health, on your race and on your 
ethnic origin. This collected information about you is called “data” or “study data” in this 
document. 
 
For the purposes of your participation in this study and the protection of your identity, your study 
doctor will assign you a unique code, such as a series of numbers and/or letters. The study doctor 
will record the study data collected from you in a report form that uses your assigned code, not 
your name. This is to protect your study data by making it anonymous for most study purposes. 
 
The data that is recorded with your assigned code rather than your name is called “key-coded data”. 
The key-coded data will be entered into the study’s computer database. Your study doctor will 
keep a confidential list linking your name to your code and only authorized persons will have 
access to this list. The ways in which key-coded data may be used and shared is described below.  
 
Some study data will identify you (such as medical records), and the ways in which this data may 
be used and shared is described below. Your key-coded data may be shared with and used by the 
following: 
 
 The study doctor and study staff 
 The study sponsor, its current or future research partners, collaborators, assignees, 
licensees or designees and their affiliates, agents, and employees 
 Other individuals and organizations that analyze or use your information in connection 
with these research activities, including laboratories and study sites (in the event you 
transfer to another study site) 
 Domestic or foreign health authorities; such as the Food and Drug Administration (FDA) 
 Other persons required by law 
 
Your key-coded data will be used in connection with this study and may also be: 
 
 Used for other current or future research involving the same drug(s), the same or related 
health conditions, or for other relevant health research; 
 Transferred to individuals or companies located outside of the country or region in which 
you reside. However, all access to the key coded data will be controlled in accordance with 
applicable laws and regulations.  
 This may include written agreements that require that the data be kept confidential and 
secure and be used only for the purposes permitted by this consent form or applicable laws 
and regulations; 
 Used in publications about this study but it will remain coded. Your identity will not be 
revealed in any compilation, study report or publication at any time. 
 
Use and Sharing of Study Data that Identifies You 
 
The use and sharing by your study doctor of study data that identifies you, such as your original 
medical records, are explained in a separate HIPAA Authorization. By signing that form, you 

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show that you give permission for the uses and sharing of this data as described in that 
document. You do not have to sign that form, but if you do not, you will not be allowed to 
participate in this study. To withdraw your HIPAA Authorization you will need to do so in 
writing as described in that document. There is a risk that your information will be given to 
others without your permission. 
 
 
What if new information becomes available? 
 
During the course of this study, we may find more information that could be important to you. 
This includes information that, once learned, might cause you to change your mind about being in 
the study. We will notify you as soon as possible if such information becomes available. 
 
What happens if you decide not to take part in this study? 
 
You should only take part in this study if you want to volunteer. You should not feel that there is 
any pressure to take part in the study. If you feel any pressure to take part in the research study 
please talk to your study doctor or the research staff. 
 
You can decide after signing this informed consent document that you no longer want to take 
part in this study. We will keep you informed of any new developments that might affect your 
willingness to continue to participate in the study. However, you can decide you want to stop 
taking part in the study for any reason at any time. If you decide you want to stop taking part in 
the study, tell the study staff as soon as you can. Any information that has been collected before 
you withdraw your authorization from the study will continue to be used for research purposes. 
 
 We will tell you how to stop safely. We will tell you if there are any dangers if you stop 
suddenly. 
 
Are there any reasons we might take you out of the study later on? 
 
Even if you want to stay in the study, there may be reasons we will need to take you out of it. You 
may be taken out of this study if: 
 
 We find out it is not safe for you to stay in the study. For example, your health may worsen 
or we may find that the experimental drug might harm you. 
 You are not taking your medication properly or are not coming for your study visits as 
scheduled. 
 The doctor feels it is not in your best interest to continue. 
 If the sponsor or investigator stops the study or your participation for any reason. 
 
You can get answers to your questions, concerns, or complaints. 
 
You have rights as a research subject.  These rights have been explained in this consent form that 
you have been given.  If you have any questions concerning your rights, talk to the investigator or 
call the Institutional Review Board (IRB), telephone (xxx) xxx-xxxx. 

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If you have any problems or questions about this study, or about your rights as a research subject, 
or about any research-related injury, contact the main study doctor, Principal Investigator, M.D. 
at (xxx) xxx-xxxx. 
 
Clinical Trial Information in Public Database 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
Statement of Participation in Research and Authorization for the Collection, Use and 
Disclosure of Health Information 
 
It is up to you to decide whether you want to take part in this study. If you want to take part, please 
read the statements below and sign the form if the statements are true. A representative of the 
<<CLINICAL SITE>>> must answer your questions completely before providing this form to 
you. You or your personal representative should read this form and understand it before signing it. 
 
I freely give my consent to take part in this study and authorize that my health information 
as agreed above, be collected/disclosed in this study. I understand that by signing this form I am 
agreeing to take part in research. I have received a copy of this form to take with me. 
 
 
Signature of Person Taking Part in Study     
 
 
 
 
 
Date 
 
 
Printed Name of Person Taking Part in Study    
 
 
 
 
 
 
 
Statement of Person Obtaining Informed Consent / Research Authorization 
 
I have carefully explained the study and consent to the person as signed above. I have taken part 
in the consent process prior to the patient’s signature and discussed in detail the study aims, 
methods, anticipated benefits, potential hazards or discomforts, and treatment alternatives. I have 
answered all questions the patient and/or family have asked. No Study procedures were initiated 
prior to consent. 
 
 
 
Signature of Person Obtaining Informed Consent / Research Authorization          Date 
 
 
Printed Name of Person Obtaining Informed Consent / Research Authorization 
 
 
 
 

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Statement of Investigator 
 
I certify that I am signing this form within seven days of the patient’s signature and prior to 
randomization and/or treatment, but after the patient’s signature has been obtained. 
 
 
Signature of Study Investigator 
 
 
 
 
 
 
 
Date 
 
 
Printed Name of Study Investigator  
 
 
 
 
 
 
 
 
 

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Addendum to the Consent 
Consent to take and store additional blood samples 
 
We are asking you to allow us to take and store additional samples of your blood. This is an 
optional test that may help us better understand who will respond to treatment with indoximod. 
  
This means we will take an additional 18 mL (about 3 teaspoons) of blood to be stored for 
subsequent (later) analysis related to the IDO enzyme. The IDO enzyme is an immune suppressing 
enzyme released by the tumor and indoximod seems to block this enzyme. 
  
These samples may be stored at NewLink Genetics Corporation within a climate controlled, 
restricted access area requiring key cards for entry.  These samples will be used for future research 
to help us better understand who may respond to treatment with indoximod. 
 
These samples will only have subject identifiers consisting of your initials followed by your study 
subject number (XX-111).  No one except your physician or clinical research team will be able to 
connect your coded health information to you. 
 
You can decide if you want us to store and use your samples for this future analysis of the IDO 
enzyme.  
 
You do not have to agree to these optional samples of blood in order to take part in the study that 
has been previously explained to you.  
 
Please initial your choice below:  
 
____ I give my consent to provide an additional 18 mL of blood for that purpose on the first day 
of each treatment cycle.  
 
____ I do not give my consent to provide an additional 18 mL of blood for that purpose. 
 
Even if you sign this consent, you have the right to withdraw your samples at any time.  To do so, 
please submit a written request to Dr. XXXXXXX at:  
Attn: Principle Investigator, MD 
Institution Name 
Address  
City, State Zip 
 
_______________________________________________________ 
Printed Name of Person Explaining Consent  
 
_______________________________________________________ 
 
___________ 
Signature of Person Explaining Consent  
 
 
 
 
 
Date 
 
 

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Expansion Study Addendum 
Why are you being asked to take part? 
You have been asked to participate in the Expansion Study because you have a tumor lesion that 
can be readily accessed through the skin by performing a core needle biopsy.  Core needle 
biopsy uses a long hollow needle to remove samples of tumor tissue. 
How many people will participate in the expansion study? 
Forty (40) patients will be asked to participate across multiple institutions.  Approximately 
<<XX>> patients will be enrolled at <<CLINICAL SITE>>>. 
What will happen during the expansion study? 
Study treatment in the Phase 2 expansion will follow the same treatment plan for Phase 2 already 
described in this consent form except for the addition of obtaining two tumor biopsies. 
Your doctor will perform a core needle biopsy one time before you start study treatment and then 
again in approximately 8 weeks (at the end of Cycle 2).   
The core needle biopsies are required for participation in the expansion study and are being 
obtained to evaluate the possible effects of the treatment on your cancer and immune system.  
 
How is a core needle biopsy done? 
 
Most needle biopsy procedures don't require any preparation on your part. However, you may be 
asked to stop taking blood-thinning medications, such as warfarin (Coumadin) or aspirin, in the 
days before your biopsy. Depending on what part of your body will be biopsied, your doctor may 
ask you not to eat or drink before the procedure. 
 
In certain cases, you may receive intravenous (IV) sedatives or general anesthetics before your 
needle biopsy. If this is the case, your doctor may ask that you fast (don’t eat) the day before 
your procedure. Tell your doctor about any medications you're taking, as you may need to stop 
taking certain medications before undergoing anesthesia. 
 
Your health care team will position you in a way that makes it easy for the doctor to access the 
area where the needle will be inserted. You may be asked to lie flat on a table. 
 
In certain cases, you may undergo imaging procedures, such as a CT scan or ultrasound. These 
allow your doctor to see the target area and plan the best way to proceed. Imaging procedures are 
sometimes done before your needle biopsy and sometimes performed during the biopsy. What 
type of imaging you'll undergo, if any, will depend on what part of your body is being biopsied. 
 

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Your health care team will clean the area of your body where the needle will be inserted. An 
anesthetic may be injected into the skin around the area to numb it. In some cases, you'll receive 
an IV sedative or other medication to relax you during the procedure.  
 
During the needle biopsy, the doctor guides a needle through your skin and into the area of the 
tumor. A sample of tumor cells is collected and the needle is withdrawn. This process may be 
repeated several times until enough cells are collected. 
 
What are the risks of the Core Needle Biopsies? 
Core needle biopsy carries a small risk of bleeding and infection at the site where the needle was 
inserted. Some mild pain can be expected after needle biopsy, though it is usually controlled with 
over-the-counter pain relievers or prescription medications. 
 
Tell your doctor if you experience: 
 
Fever 
 
Pain at the biopsy site that worsens or isn't helped by medications 
 
Swelling at the biopsy site 
 
Drainage from the biopsy site 
 
Bleeding that doesn't stop with pressure or a bandage 
 
Who will pay for the Core Needle Biopsies? 
The sponsor of this study, NewLink Genetics Corporation, will pay for these procedures as long 
as they are being completed for research purposes only and not conducted for diagnostic or 
standard of care purposes. You and/or your insurance company will be responsible for paying for 
the procedures if they were conducted as a normal occurrence for the management of your 
disease.  
 
The nature and purpose of this expansion study has been explained to me and I understand that if 
I choose to participate in this study, there will be an insertion of a needle into my body so that 
tissue can be removed. The risks of injury, infection, bleeding and other complications, despite 
precautions, have been explained to me.  
 
I freely give my consent to take part in this study. I understand that by signing this form I am 
agreeing to take part in research. I have received a copy of this form to take with me. 
 
 
Signature of Person Taking Part in Study     
 
 
 
 
 
Date 
 
 
Printed Name of Person Taking Part in Study   
 
 
 
 
 
 
 
 
 
 

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Signature of Person Explaining Consent Addendum            
 
 
 
Date 
 
 
Printed Name of Person Explaining Consent Addendum