Clinical trial NCT01834235
Conditions: Pancreatic Cancer, Adult
Keywords: Pancreatic neoplasms Pancreatic cancer Pancreatic cancer, adult Adenoma of the pancreas Carcinoma of the pancreas
Sponsor: Precision Biologics, Inc
Start date: 2013-04-01; Completion date: 2019-12-01
Enrollment: 81 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This was a Phase 1/2 multi-institution prospective open label study in which subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen received the investigational agent NEO-102 (NPC-1C).

The Phase 1 portion of this study evaluated the safety of NEO-102 in combination with Gemcitabine in a dose de-escalation design with a starting dose of 1.5 mg/kg/dose. If 2 of 6 patients experience DLT, the dose will be de-escalated to 1 mg/kg/dose to evaluate the safety of NEO-102 in combination with Gemcitabine. .

In the Phase 2 portion patients were randomized into one of two arms:

A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel

Detailed description:
During Part 1 of the study, the safe and tolerable dose of NEO-102 in combination with Gemcitabine will be determined using a dose de-escalation design. The starting dose of NEO-102 is 1.5 mg/kg/dose (Dose level 1). If 2 of 6 patients experience a DLT at the starting dose, the dose of NEO-102 will be de-escalated to 1 mg/kg/dose, and up to 6 patients will be treated at this Dose Level -1. Upon completion of the phase I study up to 90 patients be randomized to one of two arms:

A: Patients will receive NPC-1C(NEO-102) infusion at the safe dose, and nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15 ) followed by a week of rest (for a 28 day cycle).

OR B: Patients will receive on Day 1, 7 and 15 nab-paclitaxel (125 mg/m2 as a 30 minute infusion, maximum infusion time not to exceed 40 minutes) followed by gemcitabine (1000 mg/m2 as a 30 minute infusion) for 3 consecutive weeks (on Day 1, 7 and 15). NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV 30 minutes following the completion of the gemcitabine on days 1 and 15 of the 28 day cycle.

Arms: arm 1: Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest. arm 2: Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 consecutive weeks followed by a week of rest.

Patients on arm B will receive NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 4-week cycle. This will be administered 30minutes after completion of the gemcitabine infusion. arm 3: The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:

Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1.5 mg/kg IV on days 1 and 15 of a 4-week cycle. Three subjects were enrolled on this dose level and all 3 subjects completed without any dose limiting toxicity. This dose was established for the Phase 2 portion of the study. At this time FDA approved the combination of Gemcitabine and Abraxane in this patient population. Hence the Phase 2 portion added Abraxane to the regimen. arm 4: The initial portion of this protocol was a phase 1 (3+3) dose de-escalation design the initial dose of 1.5 mg/kg/dose:

Gemcitabine was administered at the dose of 1000 mg/m2 by IV infusions over 30 minutes on days 1, 8, and 15 followed in 30 minutes by NPC-1C(NEO-102) infusion at 1 mg/kg IV on days 1 and 15 of a 4-week cycle. No patients were enrolled on this arm because Dose Level 1 was determined to be safe.
Interventions: intervention 1: Gemcitabine intervention 2: nab-paclitaxel intervention 3: NPC-1C
Intervention descriptions: intervention 1: Gemcitabine IV at a dose of 1000mg/m2 on days 1, 8, and 15 of a 4 week cycle. intervention 2: Nab-paclitaxel will be administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to exceed 40 minutes) on Days 1, 7 and 15 for a 28 day cycle intervention 3: NPC-1C(NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 and 15 of a 28 day cycle. This will be administered 30 minutes after completion of the gemcitabine infusion.

Protocol documents:
Prot_SAP_000.pdf: 
1 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 
Version Date: 7/19/2016 
IND#: 100207 
Precision Biologics Protocol Number:  PB-1201 
Edition Number: 13 Amendment: L 
 
Title: A Multicenter Randomized Phase II Study of NPC-1C in Combination with Gemcitabine and nab-
Paclitaxel versus Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced 
Pancreatic Cancer Previously Treated with FOLFIRINOX  
Medical Advisor 
Philip M. Arlen, M.D., Chief Medical Officer 
Precision Biologics, Inc. 
11300 Rockville Pike, Suite 1140 
Rockville, Maryland  20852 
Cell Phone: 301-728-4883 
Tel: 301-917-6890 
FAX: 240-669-9828 
e-mail: parlen@Precision-Biologics.com 
Sponsor: 
Precision Biologics, Inc. 
11300 Rockville Pike, Suite 1140 
Rockville, Maryland 20852 
 
 
 
Investigational Agents:     
Drug Name: 
NPC-1C antibody (NEO-102), Ensituximab 
IND Number: 
100207 
Sponsor: 
PRECISION BIOLOGICS, Inc. 
Manufacturer: 
Cytovance Biologics 


2 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Précis  
Background: 
 Pancreatic cancer carries a poor prognosis with an overall 5-year relative survival rate of 
5-6%. In a recent Phase III trial the regimen of FOLFIRINOX has shown an encouraging 
outcome compared to Gemcitabine leading to the use of FOLFIRINOX as a first line 
treatment option for patients with advanced pancreatic cancer. Similarly, the combination 
of gemcitabine and paclitaxel protein-bound particles for injectable suspension (albumin-bound) 
(nab-Paclitaxel, ABRAXANE®) has demonstrated phase III survival benefit and has been FDA 
approved for the first-line treatment of pancreatic cancer. There are currently no data for either 
Gemcitabine/nab-Paclitaxel or FOLFIRINOX in the second-line setting. However a common 
extrapolation from the first-line studies has led many in the community to sequence FOLFIRINOX 
treatment followed upon disease progression by Gemcitabine/nab-Paclitaxel for patients with 
advanced pancreatic cancer with good performance status. 
 NPC-1C is a chimeric monoclonal IgG1 antibody recognizing an epitope in the polypeptide 
backbone of aberrantly glycosylated MUC5AC.   
Objectives: 
 Phase I Primary Objective 
 To determine the safety and tolerability of NPC-1C (NEO-102) monoclonal antibody 
therapy in combination with Gemcitabine as a second line therapy in subjects with 
metastatic, locally advanced unresectable or recurrent pancreatic cancer previously treated 
with FOLFIRINOX and whose tumors bind NPC-1C by at least 20% on IHC. 
COMPLETED. 
 Phase IIB Primary Objective 
 To determine whether NPC-1C (NEO-102) in combination with Gemcitabine and nab-
Paclitaxel will increase the overall survival (OS) compared to Gemcitabine and nab-Paclitaxel 
alone in patients with metastatic, locally advanced unresectable or recurrent pancreatic 
cancer previously treated with FOLFIRINOX and whose tumors bind NPC-1C by at least 
20% on IHC. 
 Secondary Objective 
To determine the safety and feasibility of NPC-1C (NEO-102) in combination with 
Gemcitabine and nab-Paclitaxel in patients with metastatic, locally advanced pancreatic 
cancer previously treated with FOLFIRINOX.  
Eligibility: 
 Subjects with measurable recurrent, locally advanced unresectable or metastatic 
adenocarcinoma of the pancreas who have progressed after primary therapy; subjects must 
have progressed after receiving FOLFIRINOX or were intolerant of FOLFIRINOX (or 
FOLFIRINOX-like regimen).  
 IHC: ≥ 20% of tumor on tissue sections must stain with NPC-1C. 


3 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 Age: ≥ 18 years of age. 
 ECOG Performance status of 0-1. 
Design/Schema: 
 This is a randomized phase II multi-institution prospective open label study in which up to 90 
evaluable subjects with measurable metastatic, locally advanced unresectable or recurrent 
pancreatic cancer who failed or did not tolerate chemotherapy with FOLFIRINOX will be 
enrolled into one of two arms, A and B.  
 
Arm* 
Gemcitabine 
(mg/m2 IV on days 1, 8, 
and 15 of a 28-day cycle) 
 
Nab-paclitaxel 
(mg/m2 IV on days 1, 
8, and 15 of a 28-day 
cycle) 
NPC-1C (NEO-102) 
(mg/kg IV every other week on 
days 1 and 15 of a 28-day cycle) 
A 
1000  
125 
1.5 
 
B 
1000  
125 
No NPC-1C 
 
*Patients will be randomized between Arms A and B. 
 


4 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
TABLE OF CONTENTS  
Précis .............................................................................................................................................. 2 
Background: .................................................................................................................................. 2 
1 
INTRODUCTION .................................................................................................................. 9 
1.1 
Study Objectives .............................................................................................................. 9 
1.1.1 
Primary Objectives.................................................................................................... 9 
1.1.2 
Secondary Objectives................................................................................................ 9 
1.1.3 
Secondary Objectives................................................................................................ 9 
1.2 
Background and Rationale: .............................................................................................. 9 
1.2.1 
Pancreatic cancer ...................................................................................................... 9 
1.2.2 
NPC-1C ................................................................................................................... 10 
1.2.3 
The rationale of combining NPC-1C (NEO-102) with Gemcitabine ..................... 14 
1.2.4 
Clinical experience with NPC-1C ........................................................................... 16 
1.2.5 
Rationale for selection of study population, treatment dose and schedule ............. 17 
1.2.6 
Status of Protocol and rationale for amendment F (February 2014) ...................... 18 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT ....................................................... 19 
2.1 
Eligibility Criteria .......................................................................................................... 19 
2.1.1 
Inclusion Criteria .................................................................................................... 19 
2.1.2 
Exclusion Criteria ................................................................................................... 20 
2.1.3 
Inclusion of Women and Minorities ....................................................................... 21 
2.2 
Screening Evaluation...................................................................................................... 21 
2.2.1 
IHC Screening Phase .............................................................................................. 21 
2.2.2 
Study Screening Phase ............................................................................................ 21 
2.3 
Registration Procedures.................................................................................................. 22 
3 
STUDY IMPLEMENTATION ............................................................................................ 22 
3.1 
Study Design .................................................................................................................. 22 
3.2 
Treatment plan................................................................................................................ 23 
3.2.1 
Treatment Dose and Schedule ................................................................................ 23 
3.3 
Dose Limiting Toxicity- COMPLETED ........................................................................ 24 
3.3.1 
Definition of Dose-limiting Toxicities (DLTs): ..................................................... 24 
3.4 
Stopping rules for safety of arm A ................................................................................. 25 


5 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
3.5 
Drug Administration ...................................................................................................... 27 
3.5.1 
NPC-1C (NEO-102)................................................................................................ 27 
3.5.2 
Nab-paclitaxel (Abraxane) ...................................................................................... 28 
3.5.3 
Gemcitabine (Gemzar) ............................................................................................ 28 
3.6 
Dosing Delays and Dose Modifications ......................................................................... 29 
3.6.1 
Gemcitabine and Nab-paclitaxel Dose Modification .............................................. 29 
3.6.2 
NPC-1C (NEO-102) Dose Modification (Arm A Only): ....................................... 30 
3.6.3 
General Guidelines for Combination Therapy modifications:................................ 31 
3.7 
ON-Study Evaluations (see study calendar)................................................................... 31 
3.7.1 
Baseline Evaluation ................................................................................................ 31 
3.7.2 
Pre-Dosing Evaluation ............................................................................................ 32 
3.7.3 
Treatment Evaluations ............................................................................................ 32 
3.8 
Study Calendar ............................................................................................................... 33 
3.9 
Criteria for Removal from Protocol Therapy and Off Study Criteria ............................ 34 
3.9.1 
Criteria for removal from protocol therapy ............................................................ 34 
3.9.2 
Off-Study Criteria ................................................................................................... 35 
3.10 
FOLLOW UP EVALUATIONS ................................................................................ 35 
4 
CONCOMITANT MEDICATIONS/MEASURES .............................................................. 35 
4.1 
Permitted Concomitant Medications .............................................................................. 35 
4.2 
Concomitant Medications NOT Permitted ..................................................................... 35 
5 
BIOSPECIMEN COLLECTION .......................................................................................... 36 
5.1 
Immunohistochemistry with NPC-1C: ........................................................................... 36 
5.1.1 
Summary of Assay: ................................................................................................. 37 
5.1.2 
Procedure for slide submission ............................................................................... 37 
5.2 
Correlative Studies for Research .................................................................................... 37 
5.2.1 
Blood Collection and Processing: ........................................................................... 37 
5.2.2 
Immunogenicity Testing (HACA) for Arm A only (to be performed at Precision 
Biologics, Inc): ...................................................................................................................... 38 
5.2.3 
Immunomonitoring of samples (Arm A only; to be performed at NCI): ............... 38 
5.2.4 
Summary of correlative studies .............................................................................. 39 
5.3 
Sample Storage, Tracking and Disposition .................................................................... 39 


6 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
6 
DATA COLLECTION AND EVALUATION ..................................................................... 40 
6.1 
Data Collection ............................................................................................................... 40 
6.2 
Response Criteria ........................................................................................................... 41 
6.2.1 
Definitions............................................................................................................... 41 
6.2.2 
Disease Parameters ................................................................................................. 41 
6.2.3 
Methods for Evaluation of Measurable Disease ..................................................... 42 
6.2.4 
Response Criteria .................................................................................................... 42 
6.2.5 
Duration of Response .............................................................................................. 44 
6.2.6 
Progression-Free Survival (PFS) ............................................................................ 45 
6.2.7 
Overall Survival (OS) ............................................................................................. 45 
6.3 
Toxicity Criteria ............................................................................................................. 45 
6.3.1 
Suspected adverse reaction ..................................................................................... 45 
7 
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
 
45 
7.1 
Definitions ...................................................................................................................... 45 
7.1.1 
Adverse Event ......................................................................................................... 45 
7.1.2 
Unexpected adverse reaction .................................................................................. 46 
7.1.3 
Serious..................................................................................................................... 46 
7.1.4 
Serious Adverse Event ............................................................................................ 46 
7.1.5 
Disability ................................................................................................................. 46 
7.1.6 
Life-threatening adverse drug experience ............................................................... 47 
7.1.7 
Protocol Deviation (NIH Definition) ...................................................................... 47 
7.1.8 
Non-compliance (NIH Definition) .......................................................................... 47 
7.1.9 
Unanticipated Problem............................................................................................ 47 
7.2 
Reporting Criteria to the Sponsor................................................................................... 47 
7.2.1 
Reporting to the Sponsor ........................................................................................ 47 
7.3 
IND Safety Reports ........................................................................................................ 49 
7.4 
Data and Safety Monitoring Plan ................................................................................... 50 
7.4.1 
Principal Investigator/Research Team .................................................................... 50 
7.4.2 
Administrative Sponsor Requirements ................................................................... 50 
7.5 
Drug accountability ........................................................................................................ 52 


7 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
8 
STATISTICAL SECTION ................................................................................................... 52 
9 
MULTI-INSTITUTAL GUIDELINES ................................................................................ 54 
9.1 
Collaborative Agreement ............................................................................................... 54 
9.2 
IRB Approvals, Amendments and Consents: ................................................................. 54 
9.3 
Patient Registration: ....................................................................................................... 54 
9.4 
Drug Distribution: .......................................................................................................... 55 
9.5 
Data Collection and Toxicity Reporting: ....................................................................... 55 
10 HUMAN SUBJECTS PROTECTIONS ............................................................................... 55 
10.1 
Rationale For Subject Selection ................................................................................. 55 
10.2 
Participation of Children ............................................................................................ 55 
10.3 
Evaluation of Benefits and Risks/Discomforts ........................................................... 55 
10.4 
Consent and Assent Process and Documentation ....................................................... 56 
10.4.1 IHC Screening Consent........................................................................................... 56 
10.4.2 Study Screening Informed Consent ........................................................................ 56 
11 PHARMACEUTICAL AND INVESTIGATIONAL DEVICE INFORMATION .............. 56 
11.1 
NPC-1C (NEO-102) Arm A only ............................................................................... 56 
11.1.1 Source: .................................................................................................................... 56 
11.1.2 Toxicity: .................................................................................................................. 57 
11.1.3 Formulation and preparation: .................................................................................. 57 
11.1.4 Stability and Storage and Infusion: ......................................................................... 58 
11.1.5 Incompatibilities: .................................................................................................... 58 
11.1.6 Reconstitution ......................................................................................................... 58 
11.1.7 Administration: ....................................................................................................... 58 
11.2 
Gemcitabine ................................................................................................................ 59 
11.2.1 Source: .................................................................................................................... 59 
11.2.2 Toxicity: .................................................................................................................. 59 
11.2.3 Formulation and preparation: .................................................................................. 60 
11.2.4 Stability and Storage: .............................................................................................. 60 
11.2.5 Administration procedures: ..................................................................................... 60 
11.2.6 Incompatibilities: .................................................................................................... 60 


8 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
11.3 
Paclitaxel Protein-Bound Particles For Injectable Suspension (albumin-bound (nab-
Paclitaxel, ABRAXANE®) ...................................................................................................... 60 
11.3.1 Source: .................................................................................................................... 60 
11.3.2 Toxicity: .................................................................................................................. 60 
12 REFERENCES ..................................................................................................................... 63 
13 APPENDICES ...................................................................................................................... 66 
13.1 
Appendix A-Performance Status Criteria ................................................................... 66 
13.2 
Appendix B: Eligibility Checklist .............................................................................. 67 
13.3 
Appendix C: NPC-1C Immunohistochemical Staining Request ................................ 70 
13.4 
Appendix D: Hypersensitivity/infusion Reaction Algorithm ..................................... 71 
13.5 
Appendix E: Summary of correlative studies ............................................................. 72 
13.6 
Appendix F: Excerpted from abraxane for injectable suspension (package insert) ... 73 
13.7 
Appendix G Investigator Agreement and Signature Page .......................................... 83 
  
 


9 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
1 INTRODUCTION 
1.1 
STUDY OBJECTIVES 
1.1.1 Primary Objectives 
 To determine whether NPC-1C (NEO-102) in combination with Gemcitabine and 
paclitaxel protein-bound particles for injectable suspension (albumin-bound) (nab-
Paclitaxel, ABRAXANE®) will increase the overall survival (OS) compared to 
Gemcitabine and nab-Paclitaxel alone in patients with metastatic, locally advanced 
pancreatic cancer previously treated with FOLFIRINOX or (FOLFIRINOX-like regimen) 
and whose tumors bind NPC-1C by at least 20% on IHC. 
1.1.2 Secondary Objectives 
To determine the safety and feasibility (as measured by futility and efficacy) of NPC-1C 
(NEO-102) in combination with Gemcitabine and nab-Paclitaxel in patients with 
metastatic, locally advanced pancreatic cancer previously treated with FOLFIRINOX or 
FOLFIRINOX-like regimen.  
 To determine the safety and tolerability of NPC-1C(NEO-102) monoclonal antibody 
therapy in combination with Gemcitabine in subjects with metastatic, locally advanced 
unresectable or recurrent pancreatic cancer who failed or did not tolerate first line 
chemotherapy of FOLFIRINOX and whose tumors bind NPC-1C. COMPLETED 
1.1.3 Secondary Objectives 
 To determine the progression free survival (PFS) and response rate (RR) of patients with 
metastatic or locally advanced unresectable or recurrent pancreatic cancer who progressed 
following or did not tolerate chemotherapy of FOLFIRINOX or FOLFIRINOX-like 
regimen when receiving the combination of NPC-1C(NEO-102) monoclonal antibody, 
Gemcitabine and nab-Paclitaxel. 
 To explore the immunologic correlates associated with the administration of NPC-1C 
(NEO-102) monoclonal antibody therapy in combination with Gemcitabine and nab-
Paclitaxel. 
1.2 
BACKGROUND AND RATIONALE: 
1.2.1 Pancreatic cancer 
It is estimated that 43,920 patients will be diagnosed with pancreatic cancer and 37,390 patients 
will die from the disease in 2012 [1]. Pancreatic cancer carries a poor prognosis with an overall 5-
year relative survival rate of 5-6% [2] [3]. Surgery remains the only chance for cure for patients 
diagnosed with resectable disease, however, only 10% of the patients present with operable disease 
[4]. Gemcitabine has been considered the first line therapy for advanced pancreatic cancer for the 
last 2 decades due to its efficacy in alleviation of disease-related symptoms and modest effect on 
overall survival (median OS 5.65 months) [5]. However, recently the regimen of FOLFIRINOX 


10 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
has shown an impressive outcome compared with Gemcitabine in a Phase III trial; median overall 
survival was 11.1 months in the FOLFIRINOX group compared to 6.8 months in the Gemcitabine 
group (hazard ratio for death, 0.57; 95% CI, 0.45 to 0.73; P<0.001). The study was restricted to 
patients with performance status of 0-1 and FOLFIRINOX was associated with an increased 
toxicity but better quality of life at 6 months. [6]. Patients who received Gemcitabine as a second 
line after they progressed on FOLFIRINOX had a median overall survival of 4.4 months. Based 
on these findings, FOLFIRINOX has emerged as a first line treatment for patients with advanced 
pancreatic cancer who have a good performance status [7].  
In the era of targeted therapy many agents have been combined with Gemcitabine as a backbone 
in advanced pancreatic cancer but with disappointing efficacy. The addition of Erlotinib (anti-
EGFR antibodies) to Gemcitabine has increased the survival over Gemcitabine alone by 0.5 
months only, which led to the FDA approval of this combination in the treatment of metastatic or 
locally advanced pancreatic cancer [8]. Other clinical trial efforts for the treatment of metastatic 
pancreas cancer including the addition of agents such as Bevacizumab (an anti VEGF-receptor 
monoclonal antibody) and Cetuximab to Gemcitabine have largely been negative[9]. In addition 
new immunotherapy targets have been identified in pancreatic cancer, which could lead to the 
development of novel therapies[10].  
The paradigm of management for advanced pancreatic cancer changed further in October 2013 
with the publication by Von Hoff et al.[10a] of the results of a randomized phase III study 
comparing the combination of nab-Paclitaxel and gemcitabine with the previous standard of 
single-agent gemcitabine, pre-FOLFIRINOX. A total of 861 patients were randomly assigned to 
nab-paclitaxel plus gemcitabine or gemcitabine alone. The median overall survival was 8.5 
months in the nab-paclitaxel/gemcitabine group as compared with 6.7 months in the gemcitabine 
group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The 
survival rate was 35% in the nab-paclitaxel/gemcitabine group versus 22% in the gemcitabine 
group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 
months in the nab-paclitaxel/gemcitabine group, as compared with 3.7 months in the gemcitabine 
group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the 
response rate according to independent review was 23% versus 7% in the two groups (P<0.001). 
There are currently no data for either gemcitabine/nab-Paclitaxel or FOLFIRINOX in the 
second-line setting. However a common extrapolation from both the first-line studies mentioned 
above has led many in the community to sequence FOLFIRINOX treatment followed upon 
disease progression by gemcitabine/nab-Paclitaxel for patients with advanced pancreatic cancer 
with good performance status. 
 
1.2.2 NPC-1C  
NPC-1C is a chimeric immunoglobulin molecule comprised from the variable region of the heavy 
chain and light chain of murine NPC-1, genetically engineered in-frame with the constant regions 
of a human IgG1 isotype.  The recombinant protein originally manufactured for use in clinical 
studies was expressed in Chinese hamster ovary (CHO) cells and purified to homogeneity under 
GMP conditions by a contract manufacturer. This NPC-1C was referred to as NEO-101.  Due to 


11 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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diminishing supplies of NPC-1C (NEO-101) and with the intent to optimize the drug product and 
its stability, a new lot of NPC-1C was manufactured to replace NEO-101 for use in clinical studies.  
This lot, referred to as NEO-102, was manufactured by Cytovance Biologics, Inc. from a CHO-M 
clone 10-23 cell line.  NEO-102 is the lot for use in this study. Extensive biocomparability studies 
were performed demonstrating that NEO-101 and NEO-102 are comparable antibody products 
with respect to purity, identity, strength and other physicochemical qualities. 
The mature, secreted chimeric IgG has 4 subunits (2 heavy chains and 2 light chains) and has a 
predicted molecular mass of 152 kDa with a pI of 8.2. NPC-1 is a monoclonal antibody derived 
from a Tumor Associated Antigen (TAA) that was used in a TAA based vaccine previously tested 
in a Phase I-II clinical trial performed in the United States [11].  This Phase I study by Hollinshead 
et al. explored the use of TAA therapy in patients with adenocarcinoma of the colon [11].  The 
TAA was derived from pooled allogeneic colon cancer specimens from multiple patients, which 
was obtained post-operatively [12].  For the Phase I cancer vaccine trial, TAA was prepared from 
tumors of 78 selected hepatitis-free donors. Vaccines were prepared by mixing 0.2 mL TAA with 
0.2 mL of complete Freund’s adjuvant (CFA).  Twenty-two patients received vaccinations with 
follow-up ranging from 3 months to 3 years (median 21 months). All patients underwent surgical 
resection, with six of eight patients with Dukes D clinically disease-free at the time of vaccination.  
Each patient received three monthly vaccinations.  Two patients received 200 g doses of TAA, 
two received 500 g doses of TAA, and 18 received 300 g doses. [13]. Although this was a small 
Phase I trial indicating the safety of the vaccine, at the median follow-up of 21 months, 82% of the 
patients were still alive, and 59% of the patients were without evidence of disease [11]. The murine 
monoclonal antibody NPC-1 was developed against an immunogenic TAA preparation from 
pooled allogeneic colon tumor tissue extracts. NPC-1 antibody was isotyped by testing culture 
medium collected from cells using isotyping strips (Amersham-Pharmacia) and by an ELISA-
based isotyping kit (BD-Pharmingen).  Results from both tests showed the mouse NPC-1 to 
express an IgG1 heavy chain and a Kappa light chain. The nucleotide sequence of the genes 
encoding NPC-1 heavy chain (HC) and light chain (LC) were determined.  These sequences were 
found to be unique by BLAST database search and a patent was filed with the USPTO (US Patent 
7,314,622, issued January 1, 2008).  The DNA sequences encoding the heavy chain and light chain 
proteins were determined twice using RNA extractions made at different times. Both sequence 
determinations resulted in the identical DNA sequences, indicating that the sequences were 
reproducible and authentic. The mouse sequences represent the basis for designing the chimeric 
NPC-1 molecule. The murine NPC-1 antibody was genetically engineered to express the mouse 
variable regions (containing the CDRs) fused in-frame with human IgG1 constant regions.  The 
resulting chimeric antibody was renamed NPC-1C and expressed in Chinese hamster ovary (CHO) 
cells, after which the 10-23 clone was selected for manufacturing the GMP-grade NPC-1C (NEO-
102) drug product.  
1.2.2.1 MUC5AC as the target antigen for NPC-1C  
The target antigen for NPC-1C has been recently determined to be a protein with similarity to 
MUC5AC, a member of the mucin gene family.  The MUC5AC gene has been reported to be 
expressed mainly in the surface epithelium of normal gastric mucosa [14] and normal airway 
epithelium [15].  Considered an oncofetal protein, MUC5AC is also expressed in the fetal and pre-
cancerous colonic mucosa, but not in normal adult colon [16] [17]. The gene was also shown to be 


12 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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overexpressed in inflammatory conditions such as Chronic Obstructive Pulmonary Disease [14] 
and H. Pylori infections of the GI tract. These conditions produce an excess mucus secretion 
associated with the abundantly glycosylated MUC5AC glycoprotein. Overexpression of 
MUC5AC has also been shown to be associated with pancreatic and colorectal cancer.  However, 
it is believed that unlike the inflammatory conditions noted above where MUC5AC is heavily 
glycosylated, in pancreas and colon tumors MUC5AC was reported to be aberrantly glycosylated 
[18] [19 ] [20]., Antibody-staining results with NPC-1C demonstrated specific immunoreactivity 
with cancer tissues from colon and pancreas patients, whereas only weak binding, if at all, was 
observed in normal pancreas or colon tissues.  Furthermore, no cross-reactivity was observed in 
other normal human tissues stained at Precision Biologics, Inc. indicating a strong positive 
correlation of the NPC-1C binding to colon and pancreas cancer tissues (Table 1). The 
immunohistochemical staining procedure has been developed into a highly reproducible, robust 
assay that will be used as part of this clinical trial. Eligibility will require that a prospective 
subject’s tumor specimen stain with NPC-1C antibodies > 20% in order to participate in the clinical 
trials. 
 
Tissue Type 
% Positive NPC-1C (n) 
Pancreatic cancer 
54% (n=126) 
Normal pancreas 
0% (n=14) 
Colorectal cancer 
53% (n=171) 
Normal colon 
27% (n=18) 
Various normal 
0% (n=115) 
Table 1: Immunohistochemistry: Human Tissues With Biotinylated NPC-1C 
 
1.2.2.2 In vitro data 
The NPC-1C antibody was tested for antibody-dependent cell cytotoxicity (ADCC) activity 
against several colorectal and pancreatic tumor cell targets in vitro [21].  The data showed that in 
a standard 4-hour 111-Indium release assay that NPC-1C facilitates the killing of the colorectal 
and pancreatic tumor cell lines that express the NPC-1C epitope on the MUC5AC-like target 
antigen, but does not react towards melanoma or prostate specificity control cell lines. These in 
vitro results demonstrate that the NPC-1C antibody is capable of directing antibody-dependent cell 
cytotoxicity in the presence of normal human PBMCs (Table 2).  The data also justified further 
pre-clinical testing of the NPC-1C candidate in anti-tumor efficacy studies using pre-established 
xenograft tumors in nude mice. 


13 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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Table 2: ADCC Assay: NPC-1C Killing Against Tumor Cell Lines 
 
1.2.2.3 Pre-clinical data for NPC-1C efficacy  
The NPC-1C was tested for anti-tumor efficacy using the human AsPC-1 pancreas tumor xenograft 
model in nude mice.  In this efficacy model, mice were implanted with human AsPC-1 tumor cells 
and allowed to establish to approximately 20-50 mm3, in approximately 4-6 days.  The treatment 
phase included intraperitoneal injection of 200 ug (10mg/kg) of research-grade NPC-1C or a 
negative control human IgG, followed on the next day with an intraperitoneal injection of IL-2-
activated normal human PBMCs (approximately 2x107 per mouse per injection). Four cycles of 


14 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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treatment were administered. As shown in Figure 1, tumor inhibition was evident during the 
treatment phase of the study, and the difference between the NPC-1C treated mice and the human 
IgG control mice was statistically significant beginning on Day 18 and continuing for the 
remainder of the study with P=0.0044 by one-way ANOVA (n=8 per group) (Figure 1: NPC-1C 
Anti-Tumor Efficacy, (AsPC-1 Model)). 
 
Figure 1: NPC-1C Anti-Tumor Efficacy, (AsPC-1 Model) 
Dark arrows indicate days of NPC-1C injection (ip), gray arrows indicate days of PBMC injection (ip), the asterisk (*) indicates 
statistically significant differences between NPC-1C treated mice with human IgG treated mice. 
1.2.3 The rationale of combining NPC-1C (NEO-102) with Gemcitabine 
Increasing evidence has been mounting to suggest that immunotherapy has the possibility of 
achieving better success when used in combination with conventional chemotherapy [22, 23]. A 
standard cytotoxic agent, Gemcitabine, not only exerts direct antitumor activity, but also mediates 
immunological effects relevant for cancer immunotherapy [24] [25] [26]. Cross-presentation of 
TAAs by DCs is essential for induction of augment CTL responses. Treatment of cancer cells and 
DCs with gemcitabine results in enhanced cross-presentation of TAAs by DCs, CTL expansion, 
and infiltration of the tumor, all of which are associated with augmented CTL [27] [28] [29] [30]. 
The increase in cross-presentation did not lead to tolerance [27] [28]. Moreover, Gemcitabine 


15 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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reduced the number of myeloid suppressor cells but did not reduce CD4+ T cells, CD8+ T cells, 
NK cells, macrophages, or B cells [31, 32] [33]. Therefore, the addition of NPC-1C (NEO-102) to 
Gemcitabine may enhance its immune effect presumably by enhancing the antibody-dependent 
cell cytotoxicity (ADCC) activity against pancreatic cancer cells. 
Since Gemcitabine is the standard of care for patients who progress on FOLFIRINOX and its 
immune efficacy could be enhanced by NPC-1C (NEO-102) antibody these two agents will be 
combined in this study. 
  
1.2.3.1 Pre-clinical data in support of NPC-1C (NEO-102) in combination with Gemcitabine  
A growth and response curve was conducted using a xenograft model using the pancreatic cancer 
cell line ASPC1 to determine the suitability as a model and the growth response to Gemcitabine 
with both 60mg/kg and 100mg/kg in preparation for the combination studies with NPC-1C 
antibody. Both 60mg/kg and 100mg/kg of Gemcitabine were relevant doses, which gave partial 
responses for tumor growth admission. A study using the ASPC1 xenograft pancreatic cell line 
that expresses the antigen recognized by NPC-1C was conducted. In this study NPC-1C was 
combined with Gemcitabine to determine any additive or synergistic activities. Gemcitabine was 
given on day 1, 8 and 15 followed by NPC-1C on day 3, 10 and 17. Human PBMC were given on 
day 4, 11 and 18. NPC-1C and Gemcitabine did not interfere with the others activity, and no 
additional toxicity was identified.  Interestingly the groups treated with the combination of NPC-
1C and 60mg/kg Gemcitabine had 3 out of 10 animals terminated on study because of ulcerated 
tumors, suggesting a potential active immunological response at the tumor site (Precision 
Biologics, unpublished data). The fact that this study showed that the combination of NPC-1C and 
Gemcitabine had no negative impact on the Gemcitabine’s efficacy, but if at all it might have a 
potential positive effect, supports the rationale to use this combination in a clinical trial. 
 
Figure 2: NPC-1C antibodies + Gemcitabine Anti-Tumor Efficacy, (AsPC-1 Model) 
Tumor volume measured on Day 1-Day 22. Blues lines indicate mice treated with Gemcitabine alone, bordeaux/red lines indicate 
mice treated with Gemcitabine + NPC-1C. Red lines indicate mice with tumor necrosis.  
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16 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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1.2.4 Clinical experience with NPC-1C  
1.2.4.1 NPC-1C Monotherapy in patients with advanced pancreatic and colorectal cancer 
A Phase I/IIA open label, multi-center dose escalation clinical trial with NPC-1C(NEO101) 
antibody was conducted in patients with advanced pancreatic and colorectal cancer who are 
refractory to standard therapy [34]. In February 2013, NEO-102 a glycoengineered reformulation 
of NEO101 for improved stability and reduced RBC agglutination, was given approval by FDA 
for use in clinical trials. A dose escalation monotherapy study has been performed with NEO-102. 
The primary objective of this study was to determine the safety and tolerability of escalating 
doses of NEO-102 monoclonal antibody in patients with advanced, recurrent or metastatic 
pancreatic or colorectal cancer.  Patients were selected based upon immunohistochemistry (IHC) 
testing for NPC-1 antigen expression.  For this purpose, archival paraffin embedded tissue was 
tested and a minimum of 20% of tissue staining positive at ≥ 2 + intensity was required for 
eligibility.  Three to six patients were treated at each dose level, 1.5 mg/kg, 2 mg/kg, 3 mg/kg and 
4 mg/kg. NEO-102 was administered intravenously (IV) on days 1, 15, 29 and 43 of a 57 day 
cycle.  Premedication with dexamethasone (10mg IV), ranitidine (50mg IV) and diphenhydramine 
(25-50 mg IV) was administered prior to each dose. Additional courses could be offered in the 
absence of dose limiting or unacceptable toxicity, progressive disease, or per patient/investigator 
discretion.  
A total of 19 patients (4 pancreatic and 15 colon cancer) received at least one dose of NEO-102 in 
the Phase I portion of this study at participating institutions. Median age was 57 years (range 32-
69), 58% (11 patients) were male, median number of prior treatment regimens was 3 (range 1+ to 
8). Preplanned dose escalation to the 4 mg/kg dose was completed and no dose limiting toxicity 
was observed in the first 3 patients.  The sixth and seventh patients receiving 4 mg/kg of NEO-102 
experienced dose limiting toxicities, grade 3 anemia and transient asymptomatic grade 3 
hyperbilirubinemia, respectively.  The fifth patient at this dose experienced a transient 
asymptomatic grade 3 hyperbilirubinemia after the 3rd dose of NEO-102 in the first course of 
therapy.  Although these events occurred after completion of dose escalation, a decision to de-
escalate to 3 mg/kg was made to ensure safety of subsequent patients enrolled.  Three additional 
patients were then treated at the 3 mg/kg dose level with 1 out of 6 patients experiencing DLT 
(grade 3 reversible hypoxia, possibly related).  Hence 3 mg/kg was established as the maximum 
tolerated dose (MTD).   
This study was subsequently expanded to include two arms for analysis of overall survival: 
patients with metastatic colorectal cancer and patients with metastatic, locally advanced 
unresectable or recurrent pancreatic cancer.   
Analysis of the patients in the colorectal cancer arm:  Fifty-four (54) patients were enrolled, one 
(1) withdrew prior to the first dose; 53 patients received ≥ 1 dose of NEO-102 and were eligible 
for toxicity evaluation. Grade 3 and 4 suspected adverse events (AEs) (reported as # events /total 
# of doses [227 doses]):  anemia (1.3%), hyperbilirubinemia (0.9%), fatigue (0.9%), and 
hemolysis, nausea, vomiting, headache, hypoxia (0.4%).  The most common grade 1-2 suspected 
AEs were anemia, fatigue, nausea, vomiting, flushing, hyperbilirubinemia, constipation, 
diarrhea, hemolysis, and dyspnea, chills. Other toxicities reported in 1 patient each included 
platelet count decrease, neutrophil decrease, AST increase, rash, hypoesthesia, malaise, gait 


17 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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disturbance, mucosal inflammation, pharyngeal edema, upper airway cough syndrome, 
hypertension, hypokalemia, B-12 deficiency, back pain, myalgia, creatinine increase, 
chromaturia, night sweats. 
 
 
Forty-eight (48) patients received ≥ 2 doses and were evaluable for the primary endpoint (OS); 
41 patients were evaluated for RECIST response.  Nine (9) patients were taken off treatment for 
other reasons, i.e. patient decision, investigator decision, and prolonged intercurrent illness.  
Only two patients were removed for treatment-related toxicity: 1 for prolonged anemia, and 1 for 
grade 3 hypoxia.  Despite advanced disease in this population, amongst patients evaluated by 
RECIST, 9/41 (22%) exhibited overall stable disease (SD) at the end of the first course (D57).  
Survival of subjects with CRC participating in the Phase 1 (15 subjects) and Phase 2 (48 
subjects) portions of this monotherapy study receiving at least two doses of NEO-102 was 6.9 
months; similar to the OS observed in subjects in the Phase 2 portion alone who received NEO-
102 at 3 mg/kg (6.6 months), with the longest survival of 30.2 months.  
Analysis of the patients in the pancreatic cancer arm:  Thirty-seven (37) patients were enrolled in 
the arm with pancreatic cancer, three (3) patients withdrew prior to the first dose; 1 patient 
withdrew during the first infusion due to investigator discretion, 33 patients received ≥ 1 dose of 
NEO-102 and were eligible for toxicity evaluation.  Grade 3 and 4 suspected adverse events (AEs) 
(reported as # events /total # of doses [90 doses]): anemia (5.6%), fatigue (2.2%), hemolysis 
(1.1%), and hyperbilirubinemia (1.1%). The most common grade 1 / 2 toxicities were anemia 
(21.1%), fatigue (14.4%), hemolysis (7.8%), nausea (6.7%), d-dimer increase, hyperbilirubinemia, 
decreased appetite, and asthenia (4.4%), allergic reaction (3.3%), LDH increase, chills, vomiting 
and diarrhea (2.2%). The following toxicities each occurred in 1 patient: decreased ALC, increase 
thrombin time, decreased reticulocytes, decreased haptoglobin, thrombocytopenia, ALP, ALT and 
AST increased, flushing, weight loss, edema, constipation, abdominal pain, dyspepsia, mucosal 
inflammation, dysgeusia, upper airway cough, hypertension, bradycardia, back pain, 
musculoskeletal pain, bruising and pruritus   
Twenty-four (24) patients were evaluable for response (received ≥ 2 doses of NEO-102).  Of these 
24 patients, the average number of prior therapies was 3.3 (range 2-6), doses of NEO-102 ranged 
from 2 to 16 doses (median = 4). Fifteen (15) patients received 4 or more doses and were evaluable 
for response; two were taken off study for clinical progression without completing tumor 
measurements, 3 patients had stable disease (SD) by RECIST after 8 weeks.  Ten (10) patients 
were removed from therapy prior to completing a full course (with evaluation at D57).  One (1) 
patient chose with withdraw after two doses, 2 patients were removed from therapy for treatment-
related toxicity (anemia) and 10 stopped treatment for disease progression. Median overall survival 
is 2.4 months (range 1-11.9+) with 3 patients still alive (as of 5-16-16). 
 
1.2.5 Rationale for selection of study population, treatment dose and schedule 
1.2.5.1 Rationale for selection of study population  
Patients with metastatic or locally advanced pancreatic cancer are currently being treated with the 
traditionally used Gemcitabine-based chemotherapy or the newly developed FOLFIRINOX 


18 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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chemo regimen in the first line setting based on the Conroy et al study [6]. Patients who progressed 
on FOLFIRINOX had a median OS of 4.4 months when they received Gemcitabine as a second 
line treatment. Our proposed study population will be similar to that treated with second line 
Gemcitabine in the Conroy et al study, as it will require patients to have received FOLFIRINOX 
as a first line treatment. This would give a reasonably comparable historical control of median OS 
(4.4 months) in the second line setting.  
1.2.6 Status of Protocol and rationale for amendment F (February 2014) 
This protocol was originally designed as a single-arm study evaluating the combination of 
Gemcitabine and NPC-1C (NEO-102) as a second line therapy in subjects with metastatic, 
locally advanced unresectable or recurrent pancreatic cancer previously treated with 
FOLFIRINOX or a FOLFIRINOX-like regimen. Three subjects were enrolled and received 
NPC-1C 1.5 mg/kg on Days 1 and 15, with Gemcitabine 1000 mg/m2 on Days 1, 8 and 15 for a 
28 day cycle.  All three subjects completed the 28 day toxicity evaluation without DLT.  
Toxicities observed included:  anemia (grade 3) possibly related to NPC-1C; fatigue (grade 3), 
hyperglycemia (grade 3) and anorexia (grade 3) unlikely related to NPC-1C; anemia (grade 3), 
thrombocytopenia (grade 4) unlikely related to NPC-1C and likely related to gemcitabine.  
Hence, the NPC-1C dose established for the Phase 2 component of this study was 1.5 mg/kg for 
subsequent subject enrollment. Although the monotherapy trial determined the MTD to be 3 
mg/kg, the decision was made to maintain the dose of NEO-102 at 1.5 mg/kg to ensure safety of 
the combined regimen.  Two additional patients were enrolled and treated in the Phase 2 
component with the combination of Gemcitabine and NPC-1C/NEO-102. The first patient 
completed six cycles of therapy and achieved stable disease post cycle 2 and post cycle 4.  The 
second patient received five cycles of therapy with stable disease after cycles 2 and 4.  All 
toxicities were mild (grade 1 or 2) with the exception of one episode of grade 3 neutropenia 
possibly related to study drug, probably related to gemcitabine.  Toxicities (grade 1 or 2) 
included nausea, vomiting, constipation, difficulty breathing, fatigue, anxiety, mucositis and 
night sweats. No serious adverse events occurred in the additional patients enrolled receiving 
NEO-102 in combination with gemcitabine.  
 
Following publication of the phase III gemcitabine/nab-paclitaxel data and FDA approval of this 
regimen, screening and enrollment to 13-C-0009 at the participating sites declined significantly. 
This was thought to reflect the altered therapeutic paradigm in pancreatic cancer whereby 
patients with good performance status are treated initially with FOLFIRINOX followed upon 
disease progression by gemcitabine/nab-paclitaxel despite the lack of supportive data for the 
latter regimen in the second line setting. It was decided to amend the study (amendment F) to 
evaluate NPC-1C in combination with the gemcitabine/nab-paclitaxel regimen that is now 
widely used. Because the original single-arm study was being benchmarked against historical 
gemcitabine-alone controls and because there are no data for gemcitabine/nab-paclitaxel regimen 
in the second-line setting, amendment G will contain a control arm of gemcitabine/nab-paclitaxel 
alone.   
Status of Randomized Phase II Study to Date (May 1, 2015):  In the current design, eligible 
patients will be randomized to either Arm A: Gemcitabine (1000 mg/m2 IV) with nab-Paclitaxel 


19 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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(125 mg/m2 IV) on days 1, 8, and 15 with NEO-102 (1.5 mg/kg) IV on days 1 and 15 of a 28-day 
cycle, or to Arm B: Gemcitabine (1000 mg/m2 IV) with nab-Paclitaxel (125 mg/m2 IV) on days 
1, 8, and 15 of a 28 day cycle.  Six patients have been randomized on this trial since it was 
approved by the FDA in spring 2014.   Three patients to each arm.  One patient randomized to 
Arm B withdrew upon randomization and did not receive any treatment on this study.  One 
patient on Arm A experienced an unrelated serious adverse event after the first dose and was 
taken off study, deemed not-evaluable.  At this time there are two patients evaluable in Arm A 
and one patient evaluable in Arm B (the other patient in Arm B is too early to 
evaluate).Toxicities have been mild (grades 1/2), anemia, hypoalbuminemia, fatigue, anorexia, 
weight loss, body rash, pruritus, fever, mucositis.  Additional toxicities probably related to the 
chemotherapy regimen but possibly related to NEO-102 include thrombocytopenia, neutropenia, 
and lymphocytopenia. The safety profile to date is acceptable.  Additional sites are being 
recruited to enhance enrollment on this study.  
2 ELIGIBILITY ASSESSMENT AND ENROLLMENT  
2.1 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria 
2.1.1.1 Subjects with measurable recurrent, locally advanced unresectable or metastatic 
adenocarcinoma of the pancreas who have progressed after primary therapy; must have 
progressed after FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it 
(including if administered in adjuvant setting). FOLFIRINOX regimen is defined as 
follows: oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg mg/m2; and 
fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour 
continuous infusion, every 2 weeks.  FOLFIRINOX –like regimen could consist of 5-
FU/leucovorin or capecitabine, combined with either irinotecan, oxaliplatin or both.  
FOLFIRINOX intolerance is defined as inability to tolerate the FOLFIRINOX regimen 
due to side effects and or toxicities determined by the treating medical oncologist. 
The histology of the primary tumor should be confirmed at NCI or the other participating 
sites. 
2.1.1.2 IHC: ≥ 20% of tumor on tissue sections must stain with NPC-1C. 
2.1.1.3 Age: ≥ 18 years of age. 
2.1.1.4 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 
A). 
2.1.1.5 Have an anticipated life expectancy of greater than 8 weeks. 
2.1.1.6 Patients must have recovered from any acute toxicity related to prior therapy. Toxicity 
should be ≤ grade 1 or ≤ grade 2 for peripheral neuropathy, or returned to baseline.  
2.1.1.7 If female, is post-menopausal, surgically sterilized or willing to use an effective method 
of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with 
spermicide, or condom with spermicide, or abstinence) for the duration of the study and 


2 0  
A M ultice nter r a n d o mize d p h ase II St u dy of N P C- 1 C i n C o m bi n ati o n wit h Ge mcit a bi ne a n d n a b- P aclit axel vers us 
Ge mcit a bi ne a n d n a b- P aclit axel al o ne i n P atie nts wit h Met ast atic or L oc ally A dv a nce d P a ncre atic C a ncer 
Previ o usly Tre ate d wit h F O L FI RI N O X  
 
C O N FI D E N TI A L:  
N O T T O B E DI S C L O S E D WI T H O U T P E R MI S SI O N F R O M P R E CI SI O N BI O L O GI C S F O R Q U A LI FI E D 
I N V E S TI G A T O R S A N D T H EI R I R B S O N L Y 
Pr ot o c ol E diti o n 1 3 
Rev. 7/ 1 9/ 2 0 1 6 
f or 3 m o nt hs after t he e n d of treat me nt.  If male, h as a gree d t o use barrier met h o d f or 
c o ntrace pti o n f or t he d urati o n of t he st u d y a n d f or 3 m o nt hs after t he e n d of treat me nt. 
2. 1. 1. 8  Patie nt m ust be willi n g t o si g n a writte n i nf or me d c o nse nt 
2. 1. 1. 9  La b orat or y tests meet mi ni m u m safet y re q uire m e nts: 
 He m o gl o bi n ≥ 8. 5 g/ d L ( ma y b e recei vi n g s u p p orti ve t hera p y) 
 A N C ≥ 1, 5 0 0/ u L 
 P latelets ≥ 1 0 0 K/ u L 
 T ota l bilir u bi n ≤ 2 m g/ d L  
 A L T/ A S T ≤ 3 ti mes U L N or ≤ 5 ti mes U L N i n t he setti n g of li ver metastas es 
 C reati ni ne ≤ 1. 5 m g/ d L or creati ni ne cleara n ce ( Clcr) > 4 0 m L/ mi n/ 1. 7 3 m2 f or 
patie nts wit h creati ni ne l e vels a b o ve i nstit uti o nal n or mal, a s calc ulat e d b y t he 
C oc kcr oft Ga ult f or m ula a n d wei g hte d b y b o d y s urface area; i.e.: 
Cl cr (fe mal es) = = 1 4 0 - a ge
( 
) ´ A B W
S Cr ´ 7 2
´ 0. 8 5 ´
1. 7 3 m 2
pt's B S A ( m 2 )
 
Cl cr ( males) = = 1 4 0 - a ge
( 
) ´ A B W
S Cr ´ 7 2
´
1. 7 3 m 2
pt's B S A ( m 2 )
 
A B W, act ual b o d y w ei g ht; B S A, b o d y s urface area 
2. 1. 2  E x cl usi o n Criteria 
2. 1. 2. 1  Patie nts w h o recei v e d sec o n d li ne c he m ot hera p y after pr o gressi n g o n or n ot t olerati n g 
treat me nt wit h F O L FI RI N O X. Pri or a dj u va nt/ ne oa dj u va nt ge mcita bi ne or ge m cita bi ne-
ba se d ra di ati o n will n ot be c o u nte d as first li ne t hera p y.  
2. 1. 2. 2  Patie nts wit h k n o w n brai n metastases s h o ul d be e x cl u de d fr o m t his cli nical trial beca use 
of t heir p o or pr o g n osis a n d beca use t h e y ofte n d e vel o p pr o gressi ve n e ur ol o gic 
d ysf u n cti o n t hat w o ul d c o nf o u n d t he e val uati o n of ne ur ol o gic a n d ot h er a d verse e v e nts. 
2. 1. 2. 3  A n y maj or s ur ger y wit hi n f o ur wee ks bef ore e nr oll me nt. 
2. 1. 2. 4  Greater t ha n gra de 2 as cites at ti me of e nr oll me nt. 
2. 1. 2. 5  Patie nts w h o:  
 R ecei ve d Ge mcita bi ne f or palliati ve treat me nt; or  
 R ecei ve d Ge mcita bi ne f or rec urre nt or m etastatic disease; or  
 Is wit hi n 3 m o nt hs of recei vi n g Ge mcita bi ne i n t he a dj u va nt/ ne o-a dj u va nt  setti n g. 
2. 1. 2. 6  U nc o ntr olle d c o nc o mita nt ill ness i ncl u di n g, b ut n ot li mite d t o, o n g oi n g or acti ve 
i nfecti o n, s y m pt o matic c o n gesti ve h eart fail ure, u nsta ble a n gi na pect oris, or car di ac 
arr h yt h mia.  


21 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
2.1.2.7 Serious medical or psychiatric illness, that could, in the Investigator’s opinion, 
potentially interferes with the completion of treatment according to this protocol. 
2.1.2.8 Patients must not have other invasive malignancies within the past 3 years (with the 
exception of non-melanoma skin cancers or non-invasive bladder cancer). 
2.1.2.9 Pregnant or breast-feeding 
Since the effects of NPC-1C on the developing human fetus and nursing infants are 
unknown and potentially harmful, women of child-bearing potential must agree to use 
adequate contraception (hormonal or double barrier method of birth control or complete 
abstinence) prior to study entry, for the duration of study participation, and for three 
months after the last dose of investigational agent. Should a woman become pregnant 
or suspect she is pregnant while participating in this study, she should inform her 
treating physician immediately. 
2.1.2.10 Any chemotherapy, or systemic corticosteroids within 2 weeks before study entry. 
2.1.2.11 Patients who have acquired, hereditary, or congenital immunodeficiencies 
including cellular immunodeficiencies, hypogammaglobulinemia and 
dysgammaglobulinemia. 
2.1.2.12 Prior history of a documented hemolytic event. 
2.1.2.13 History of hypersensitivity to human or mouse antibody products. 
2.1.2.14 Patients with a known history of HIV are excluded due to the possibility that 
Gemcitabine/nab-paclitaxel or NPC-1C(NEO-102) may worsen their condition and the 
likelihood that the underlying condition may obscure the attribution of adverse events 
with respect to Gemcitabine/nab-paclitaxel or NPC-1C(NEO-102). 
2.1.3 
Inclusion of Women and Minorities 
Men and women of all races and ethnic groups are eligible for this trial. 
2.2 
SCREENING EVALUATION 
Prospective subjects will be screened for inclusion in the study in two phases: IHC screening and 
Study Screening.   According to procedures determined by each clinical study site’s IRB, 
informed consent for both screenings may be obtained with either one document or with two 
separate documents. 
2.2.1 IHC Screening Phase 
IHC staining of the tumor on tissue sections with NPC-1C may be obtained at any time 
prior to further eligibility screening for this study. Subjects who sign the IHC Screening 
informed consent document will be entered on the IHC Screening Log sheet.  IHC 
Screening informed consent may be obtained via phone consent according to institutional 
IRB policy.  The IHC will be performed and interpreted at UT Southwestern Medical 
Center CLIA certified central lab (see Section 5.1).  
2.2.2 Study Screening Phase 


22 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
If IHC demonstrates tissue stain ≥ 20% positive for NPC-1C antibody/antigen target, subjects 
will be required to sign the Protocol Informed Consent document and will be entered on the 
Study Screening Log Sheet and proceed to undergo a complete eligibility evaluation. 
2.2.2.1 History and physical exam with vital signs, body weight and height (obtained within 21 
days prior to enrollment). 
2.2.2.2 Laboratory evaluation (obtained within 21 days prior to enrollment) 
 Hematological profile: CBC with differential and platelet count, PT, aPTT, 
fibrinogen. 
 Biochemical profile: electrolytes, BUN, creatinine, AST, ALT, ALP, total bilirubin, 
calcium, phosphorus, albumin, magnesium, uric acid, albumin, and lactate 
dehydrogenase (LDH). 
 Pregnancy test for women of childbearing potential. 
2.2.2.3 Imaging studies (obtained within 28 days prior to enrollment):  
 CT scan of chest, abdomen and pelvis  
 MRI if unable to obtain CT scan 
2.2.2.4 Electrocardiogram (obtained within 28 days prior to enrollment). 
2.3 
REGISTRATION PROCEDURES 
Subjects at all of the participating sites who are evaluated and determined to be eligible will have 
Eligibility Checklist completed (Appendix C, or comparable study site registration form) 
according to source documentation, and e-mailed (preferred) or faxed to the Medical Advisor 
(Phil Arlen, M.D.) of the Sponsor at: cell phone: 301-728-4883; Fax: 240-669-9828; or e-mail 
parlen@Precision-Biologics.com, with email cc’d to azaki@Precision-Biologics.com, 
kcui@Precision-Biologics.com, smavroukakis@Precision-Biologics.com, prior to initiation of 
treatment with study drug.  Subjects will be identified only by the subject initials.  Once the 
Sponsor Medical Advisor reviews and approves eligibility (by e-mail or fax) the Sponsor 
submits the eligibility form to the NCI Central Registration Office where the randomization # 
and the subject identification number will be assigned. This information is returned to the 
Sponsor who provides approval to the site for the subject to proceed to treatment.   
3 STUDY IMPLEMENTATION 
3.1 
STUDY DESIGN 
This is a randomized phase II multi-institution prospective open label study in which up to 94 
subjects with measurable, metastatic, locally advanced unresectable or recurrent pancreatic cancer 
who failed or did not tolerate chemotherapy with FOLFIRINOX or a FOLFIRINOX-like regimen 
will be enrolled into one of two arms, A or B. Ninety evaluable patients can be treated on this trial; 
in order to allow for a very small number of inevaluable patients, the accrual ceiling will be set at 
94 patients. 
 
 


23 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 
Study Design and Drug Administration 
Arm A and Arm B 
 
 
3.2 
TREATMENT PLAN 
Patients will be randomized between Arms A and B, i.e. the combination of gemcitabine and 
nab-paclitaxel with or without the addition of the experimental agent NPC-1C (NEO-102) 
respectively. Because NPC-1C (NEO-102) has been established to be safe when given with 
gemcitabine alone but not the combination of gemcitabine and nab-paclitaxel, stopping rules for 
safety will be adhered to for the first N=6 patients randomized to Arm A.   
3.2.1 Treatment Dose and Schedule 
Arm* 
Gemcitabine 
(mg/m2 IV on days 1, 8, 
and 15 of a 28-day cycle) 
 
Nab-paclitaxel 
(mg/m2 IV on days 1, 
8, and 15 of a 28-day 
cycle) 
NPC-1C (NEO-102) 
(mg/kg IV every other week on 
days 1 and 15 of a 28-day cycle) 
A 
1000  
125 
1.5 
 
B 
1000  
125 
No NPC-1C 
 
*Patients will be randomized between Arms A and B. 


24 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Table 3: Schedule 
 
All patients will receive nab-paclitaxel followed by gemcitabine. Nab-paclitaxel will be 
administered at a dose of 125 mg/m2 as a 30 minute infusion (maximum infusion time not to 
exceed 40 minutes) followed by 1000 mg/m2 gemcitabine as a 30 minute infusion for 3 
consecutive weeks followed by a week of rest (treatment on days 1, 8, and 15, during a 28-day 
cycle for both treatment arms A and B).  
Patients on arm A will receive NPC-1C (NEO-102) infusion at a dose of 1.5mg/kg IV on days 1 
and 15 of a 4-week cycle. This will be administered 30 minutes after completion of the gemcitabine 
infusion.  
Gemcitabine, nab-paclitaxel and NPC-1C (NEO-102) doses will be calculated using weight or body 
surface area (BSA) based on the height and weight obtained during screening, unless body weight 
on Day 1 of a cycle increases or decreases greater than 10% from the weight measured during 
screening. If body weight changes >±10% from the screening weight measurement, obtained 
before cycle 1, doses will be recalculated based on the weight measured on Day 1 of repeated 
treatment cycles.   
 
Three patients will be tested at dose level 1 (NPC-1C (NEO-102) 1.5 mg/kg) and if 0/3 or 1/3 has 
a DLT, then three more will be enrolled at this level; if 0-1 of 6 has a DLT, this will be the dose 
used in the expansion phase. If 2+/6 has a DLT at 1.5 mg/kg, then the next cohort of 3 patients 
will be enrolled at dose level -1 (1.0 mg/kg). If 0/3 or 1/3 has a DLT, then 3 additional patients 
will be enrolled at this level; if 0-1 of 6 has a DLT at 1.0 mg/kg, then the expansion cohort will be 
conducted using 1.0 mg/kg. If 2-3 patients in the first 3 treated at 1.0 mg/kg have a DLT, or 2+/6 
at 1.0 mg/kg have a DLT then the study will stop accrual. COMPLETED. 
3.3 
DOSE LIMITING TOXICITY- COMPLETED 
3.3.1 Definition of Dose-limiting Toxicities (DLTs): 
3.3.1.1 Dose limiting toxicity 
 Grade 3 or higher non-hematological toxicity considered related to the combination 
of NPC-1C (NEO-102) and Gemcitabine will be defined as a DLT. 
 Grade 4 hematologic toxicities due to NPC-1C (NEO-102) or the combination 
therapy that does not resolve to ≤ grade 2 after appropriate treatment with 
filgrastim, or blood transfusion within 14 days after holding the treatment. 
Toxicities related to Gemcitabine alone will be treated according to modifications 
specified in section 3.5.1. 
 Any grade 3 or higher hematological or non-hematological toxicity considered 
related to (possibly, probably or definitely) NPC-1C (NEO-102), except transient 
known toxicity related to NPC-1C (NEO-102) infusion including fatigue, local 
reactions, flu-like symptoms, fever, and headache.  To be considered a DLT 
exception, these toxicities must recover to grade 1 or less within 8 hours after 
standard supportive treatment. 


25 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 
3.3.1.3 Exclusions to Dose Limiting Toxicities- COMPLETED 
 Grade 3 electrolyte toxicities that can be corrected to Grade 1 or less within 24 
hours will not be considered dose limiting.  
 Grade 3 hypertension that can be controlled with oral medications and does not 
require treatment delay for > 7 days will not be considered a DLT.  
 Grade 3 diarrhea will only be considered dose-limiting if it is refractory to anti-
diarrhea medications and unable to be corrected to Grade 1 or less within 48 hours. 
 Grade 3 nausea and vomiting will only be considered dose-limiting if it is 
refractory to anti-emetic therapy and unable to be corrected to Grade 1 or less 
within 48 hours. 
 Grade 3 rise in creatinine, not corrected to Grade 2 or less after 2 liters of 
intravenous fluids within 24 hours, will be considered dose limiting.  
 Grade 3 elevation in AST/ALT will only be considered dose limiting if they are 
also ≥ 1.5 times the baseline level. (This is because patients who have liver 
metastases with Grade 2 transaminase levels are eligible for study entry). 
 Grade 3 elevation on ALP (Alkaline phosphatase) will not be considered a DLT. 
 Grade 3 hypoalbuminemia will not be considered a DLT. 
 Grade 3 lymphopenia will not be considered a DLT.  
 Grade 3 rash will not be considered dose limiting unless it does not return to ≤ 
Grade 2 after 1 week of symptomatic treatment. 
 
Three patients must complete at least 1 cycle of therapy (Day 28 of Cycle 1) prior to considering 
treating 3 more patients on the same dose level or on the next dose level. Accordingly, no more 
patients will be treated until at least three patients have completed the first cycle. Determination 
of DLT for the purpose of dose de-escalation enrollment will be based on toxicities observed in 
the first 28 days of treatment (cycle 1) and must be considered at least possibly related to NPC-
1C(NEO-102) or the combination of NPC-1C(NEO-102) and Gemcitabine. Since the attribution 
of toxicities between the two drugs is difficult to determine, the investigator discretion is permitted 
to determine which drug is the source for a given toxicity.  
 
 
3.4 
STOPPING RULES FOR SAFETY OF ARM A 
3.4.1.1 Stopping rules: 
 If ≥2 of the first 6 patients on Arm A experience any one of the following, enrollment 
will be suspended pending IRB and FDA consultation on how to proceed: 
 Grade 3 or higher non-hematological toxicity considered related to the addition of 
NPC-1C(NEO-102) to the Gemcitabine/nab-Paclitaxel combination will be defined 
as a DLT with the exception of all expected toxicities clearly attributed to the 
Gemcitabine/nab-paclitaxel combination. If not considered to be related to the 
addition of NPC-1C (NEO-102) then refer to dose modifications as per Section 3.6. 


26 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 Grade 4 hematologic toxicities due to NPC-1C (NEO-102) or the combination 
therapy that does not resolve to grade ≤2 after appropriate treatment with filgrastim, 
or blood transfusion within 14 days after holding the treatment.  
 Grade 2 or greater hemolysis as defined in Section 3.4.1.3. 
3.4.1.2 Exclusions to stopping rules: 
 Grade 3 electrolyte toxicities that can be corrected to Grade 1 or less within 24 
hours will not be considered dose limiting.  
 Grade 3 hypertension that can be controlled with oral medications and does not 
require treatment delay for > 7 days will not be considered a DLT.  
 Grade 3 diarrhea will only be considered dose-limiting if it is refractory to anti-
diarrhea medications and unable to be corrected to Grade 1 or less within 48 hours. 
 Grade 3 nausea and vomiting will only be considered dose-limiting if it is 
refractory to anti-emetic therapy and unable to be corrected to Grade 1 or less 
within 48 hours. 
 Grade 3 rise in creatinine, not corrected to Grade 2 or less after 2 liters of 
intravenous fluids within 24 hours, will be considered dose limiting.  
 Grade 3 elevation in AST/ALT will only be considered dose limiting if they are 
also ≥ 1.5 times the baseline level. (This is because patients who have liver 
metastases with Grade 2 transaminase levels are eligible for study entry). 
 Grade 3 elevation on ALP (Alkaline phosphatase) will not be considered a DLT. 
 Grade 3 hypoalbuminemia will not be considered a DLT. 
 Grade 3 lymphopenia will not be considered a DLT.  
 Grade 3 rash will not be considered dose limiting unless it does not return to ≤ 
Grade 2 after 1 week of symptomatic treatment. 
3.4.1.3 Hemolysis Evaluation  
If hemoglobin drops greater than 1gm/dL then an evaluation should be performed for evidence of 
hemolysis, which may include direct antiglobulin test (DAT) (also known as direct Coomb’s 
test), schistocytes smear, serum haptoglobin and/or urinalysis. 
In addition to the definition in CTCAEv4.0, hemolysis will be graded using the following 
expanded guideline: 
 Grade 1: Laboratory evidence of hemolysis with no increase in creatinine serum levels 
above normal limits. 
 Grade 2: Laboratory evidence of hemolysis of a grade 2 or  Any hemolysis with Grade 1 
creatinine elevation  
 Grade 3: One of the following: 
o Any laboratory evidence of hemolysis and Grade 2 creatinine elevation 
o Any laboratory evidence of hemolysis and Grade 3 thrombocytopenia 
o Any laboratory evidence of hemolysis with more than a 3 gm/dL drop in hemoglobin 
requiring transfusion or steroids (or CTCAE hemoglobin level ≥ Grade 3). 


27 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 Grade 4: Any laboratory evidence of hemolysis requiring urgent medical intervention and 
one of the following: 
o Grade 3 creatinine level 
o Grade 4 platelets 
o Hemodynamic instability 
3.5 
DRUG ADMINISTRATION 
3.5.1 NPC-1C (NEO-102) 
3.5.1.1 NPC-1C (NEO-102) Drug Administration  
All treatments will be administered on an outpatient basis except when admission is required for 
any reason.  NPC-1C (NEO-102) will be administered approximately 30 minutes after the 
Gemcitabine infusion is completed (which will follow the nab-paclitaxel).  
In Arm A only: Twenty (20) to 30 minutes prior to the start of each NPC-1C (NEO-102) infusion, 
all patients will receive the following pre-medications: 
 Dexamethasone 10 mg IV  
 Benadryl 50 mg IV (but can be reduced to 25 mg in case of sensitivity)  
 Ranitidine 50 mg IV or equivalent 
After completing pre-medications, NPC-1C (NEO-102) will be administered by intravenous 
continuous infusion in 250 mL of 0.9% sodium chloride USP using either a 0.20 or 0.22 non (or 
low) protein binding micron filter with a portable pump. The attachment of the infusion pump 
administration set to the i.v. bag and transport of the study drug to the patient will be performed 
as per standard study site procedures. Infusions of NPC-1C (NEO-102) will initially be 
administered at 0.5 mg/min.  If the patient develops an infusion reaction related to NPC-1C (NEO-
102), then the guidelines in Appendix D: Hypersensitivity Infusion Reaction Algorithm will be 
followed. Infusion rates may be increased as tolerated in 0.5 mg/min increments every 30 minutes 
to a maximum rate of 4 mg/min. Subsequent doses may be administered at the highest tolerated 
rate of infusion, and/or adjusted based on patient tolerance.  
3.5.1.2  Vital Sign Monitoring (including blood pressure, pulse, respiratory rate) 
  Pre infusion of study drug. 
 Every 15 minutes (± 5 minutes) from start of infusion, times two (2). If vital 
signs are stable and no evidence of an adverse reaction is noted, vital signs can 
resume hourly until completion of infusion. 
 If infusion of study drug is interrupted at any time, vital signs should continue to 
be taken every 15 minutes (± 5 minutes) during the interruption period and until 
one hour after the time infusion of study drug is re-started.  Vital signs will 
continue to be assessed every 15 minutes until stable, at which time vital signs 
will be taken hourly until 1 hour after the completion of infusion.  During 
hospitalization, vital signs will be taken and documented every 6-8 hours, or as 
clinically indicated. 


28 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
3.5.1.3 NPC-1C (NEO-102) Infusion Reactions 
 If the patient experiences a grade 2 or 3 adverse reaction during infusion, the infusion will 
be stopped and the patient will be treated accordingly as in Appendix E. Antipyretic, 
antihistamine and other therapies can be administered as indicated. If appropriate, the 
infusion may be restarted at half of the previous rate when the patient is able to continue. 
The infusion rate for the subsequent doses may be initiated at the highest tolerated rate. 
 Patients who experience a grade 4 hypersensitivity reaction will be taken off the treatment 
with NPC-1C (NEO-102). The patient will be removed from the protocol and will be 
continued on Gemcitabine/Nab-paclitaxel as a standard of care therapy.  
 Infusion reactions will be recorded as AEs in the case report form. Interventions should be 
documented as concomitant medications or concomitant treatments as appropriate. 
3.5.2 Nab-paclitaxel (Abraxane) 
Patients do not require premedication prior to Nab-paclitaxel administration, as hypersensitivity 
reactions are not expected, though initial antiemetic prophylaxis is recommended due to 
administration of gemcitabine following Nab-paclitaxel treatment.  
 
If a severe hypersensitivity reaction occurs, the infusion should be stopped and not restarted as 
hypersensitivity reactions to Nab-paclitaxel can sometimes be fatal. For grade 1 or 2 
hypersensitivity reactions, subsequent cycles may be administered using the premedication 
regimen typically used in the institution for Taxol. 
 
Nab-paclitaxel will be administered according to the product labeling information, by 
intravenous infusion at a dose of 125mg/m2 over approximately 30 minutes not to exceed 40 
minutes. 
 
3.5.3 Gemcitabine (Gemzar) 
3.5.3.1 Gemcitabine Administration 
Gemcitabine will generally be administered on an outpatient basis except when admission is 
required for any reason. Thirty minutes to one hour prior to the start of each Gemcitabine infusion, 
all patients will receive antiemetic primary prophylaxis: (preferred agents) Ondansetron 8 mg IV 
or 16–24 mg PO or Granisetron 2 mg PO or 1 mg IV for 1 dose. 
After completing pre-medication, Gemcitabine will be administered according to its product 
labeling information, by intravenous infusion at a dose of 1000 mg/m2 over approximately 30 
minutes. 
3.5.3.2 Special Precautions  
Flu-type symptoms are reported for about 20% of patients. This includes fever, headache, back 
pain, chills, myalgia, and asthenia. Malaise and sweating are also commonly reported. Flu like 
symptoms will be treated symptomatically with acetaminophen and hydration as appropriate.   
 


29 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
3.6 
DOSING DELAYS AND DOSE MODIFICATIONS 
3.6.1 Gemcitabine and Nab-paclitaxel Dose Modification 
3.6.1.1 Gemcitabine and Nab-paclitaxel dosage adjustments for hematological toxicities 
Gemcitabine and Nab-paclitaxel dosage adjustments for hematological toxicities are based on the 
granulocyte and platelet counts. Gemcitabine and Nab-paclitaxel dosage should be modified 
according to institutional standards of care, the Abraxane package insert located at: 
(http://www.abraxane.com/downloads/Abraxane_PrescribingInformation.pdf)  
specifically,(Table 4 Dose Recommendation and Modifications for Neutropenia and/or 
Thrombocytopenia at the Start of a Cycle or within a Cycle for Patients with Adenocarcinoma of 
the Pancreas and Table 5 Dose Modifications for Other Adverse Drug Reactions in Patients with 
Adenocarcinoma of the Pancreas) (select pages from package insert are included in Appendix F) 
and the investigator discretion.  Toxicities will be graded using the NCI CTCAE Version 4.0. 
Two levels of dose modifications are permitted (according to the criteria listed in Table 3: Dose 
Level Reductions for Patients with Adenocarcinoma of the Pancreas contained in the Abraxane 
package insert (See Appendix F).  
Based on experience in administering the Gemcitabine and nab-paclitaxel to patients after first 
line therapy with FOLFIRINOX, the majority of patients require dose delays, skipped doses and 
dose modifications35.   If dosing modifications, dose delays or doses are skipped during Cycle 1 
due to toxicity attributed to Gemcitabine/nab-paclitaxel, subsequent cycles MAY be given at the 
investigator’s discretion as:  
Gemcitabine: (1000 mg/m2 IV on days 1 and 15 of a 28-day cycle) 
Nab-paclitaxel (125 mg/m2 IV on days 1 and 15 of a 28-day cycle) 
With (ARM A) or without (ARM B) NPC-1C (NEO-102) (1.5 mg/kg IV on days 1 and 15 of a 
28-day cycle). 
If a toxicity requiring dose modification occurs following the second dose reduction of either 
study drug, further treatment should be discontinued. Any further dose modification requires 
prior Sponsor approval. 
Exceptions to the need for dose-modification due to treatment-related non-hematologic toxicities 
are the following:  
 Grade 3/4 electrolyte toxicities that can be corrected to Grade 1 or less within 24 
hours.  
 Grade 3 hypertension that can be controlled with oral medications and does not 
require treatment delay for > 7 days.  
 Grade 3 diarrhea, nausea and vomiting unless refractory to anti-emetic therapy and 
unable to be corrected to Grade 1 or less within 48 hours. 
 Grade 3 rise in creatinine, not corrected to Grade 2 or less after 2 liters of 
intravenous fluids within 24 hours.  
 Grade 3 elevation in AST/ALT unless also ≥ 2 times the baseline level. (This is 
because patients who have liver metastases with Grade 2 transaminase levels are 
With doses modified as 
needed, as described above 


30 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
eligible for study entry). 
 Grade 3/4 elevation on ALP (Alkaline phosphatase). 
 Grade 3/4 hypoalbuminemia. 
 Grade 3 rash unless it does not return to ≤ Grade 2 after 1 week of symptomatic 
treatment. 
If doses of gemcitabine/nab-paclitaxel are held/skipped for chemotherapy-related 
toxicity in patients assigned to Arm A, patients may receive the scheduled dose of NPC-
1C (NEO-102) regardless of skipping the dose of gemcitabine/nab-paclitaxel. If a patient 
in Arm A discontinues gemcitabine/nab-paclitaxel due to gemcitabine/nab-paclitaxel 
toxicity, patients may continue to receive NEO-102 alone, at the PI discretion, according 
to protocol schedule until the patient meets off treatment criteria (see Section 3.9). 
  
3.6.1.2 Peripheral Neuropathy 
Nab-paclitaxel treatment should be withheld in patients who experience grade 3 
peripheral neuropathy until neuropathy resolves to grade ≤2. Gemcitabine and NPC-1C 
administration can continue during this period. Nab-paclitaxel treatment may be 
resumed at the next lower dose level in subsequent cycles after the peripheral 
neuropathy improves to grade ≤2. For recurrence of severe (grade 3) one additional dose 
reduction may be made at the next lower dose level in subsequent cycles. If grade 3 
peripheral neuropathy recurs after a second dose reduction treatment with nab-Paclitaxel 
must be discontinued, but patients may remain on protocol therapy with Gemcitabine 
with or without NPC-1C. 
3.6.1.3 Supportive treatment for hematological toxicities: If the dosage of Gemcitabine/nab-
paclitaxel is held due to grade 4 neutropenia, filgrastim may be given at a dose of 5- 10 
mcg/kg (SC) daily during that cycle and after every Gemcitabine administration in the 
following cycles, at the discretion of the PI.  The first dose of filgrastim should not be 
administered less than 24 hours following Gemcitabine/nab-paclitaxel, and filgrastim 
should not be administered within 24 hours before giving Gemcitabine/nab-paclitaxel.  
Calculated filgrastim doses may be rounded by ±10% to use the most economical 
combination of available products (commercially available products contain 300 mcg or 
480 mcg). Blood transfusion and platelets transfusion will be allowed for grade 3-4 
anemia and thrombocytopenia.  
3.6.1.4 Supportive treatment for non-hematological toxicities: supportive treatment with IV 
fluid, anti-emetics, anti-diarrhea and acetaminophen will be administered as indicated. 
In the case of flu like symptoms due to Gemcitabine infusion, patients may be treated with 
acetaminophen.  If the treatment with Gemcitabine/nab-paclitaxel is held for > 21 days due 
to chemotherapy related toxicity, patients in Arm A may continue to receive NPC-1C 
(NEO-102) on schedule during subsequent cycles.  
 
3.6.2 NPC-1C (NEO-102) Dose Modification (Arm A Only): 
3.6.2.1 NPC-1C (NEO-102) expected adverse events 


31 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
The most commonly reported clinical toxicities due to the use of NPC-1C (NEO-102are 
discussed in Section 1.2.4. 
3.6.2.2 NPC-1C (NEO-102) dosage adjustments for hematological and non-hematological 
toxicities 
 For all grade 3 non-hematologic toxicities and hematologic toxicities that is determined 
to be related to NPC-1C (NEO-102), NPC-1C (NEO-102) will be held until toxicities 
resolve to ≤ grade 1 for non-hematologic toxicities and hematological toxicities. 
 Treatment for each specific toxicity will be administered per standard recommended 
therapy, as appropriate. Infusion reactions will be managed according to Appendix D. 
 After the resolution of toxicities to ≤ grade 1 for non-hematologic toxicities and 
hematological toxicities, NPC-1C (NEO-102) will be administered in the following 
cycles as follows: 
o If NPC-1C (NEO-102) is being administered at 1.5 mg/kg, the dose will be 
reduced to 1 mg/kg in the following cycles.  
o If NPC-1C (NEO-102) is being administered at 1 mg/kg, no further dose 
reduction in NPC-1C (NEO-102) will be allowed. NPC-1C (NEO-102) will be 
discontinued and the patient can continue to receive Gemcitabine/nab-paclitaxel. 
Accordingly, the patient will be followed on study as indicated in section 3.8. 
 If the treatment with NPC-1C (NEO-102) is delayed for > 14 days due to adverse events 
attributed (at least probably) related to NPC-1C (NEO-102) then NPC-1C (NEO-102) 
will be discontinued and the patient can continue to receive Gemcitabine and nab-
paclitaxel. Accordingly, the patient will be followed on study as indicated in section 3.8. 
3.6.3 General Guidelines for Combination Therapy modifications: 
 Investigator discretion is permitted to determine which drug is the source for a given 
toxicity and to adjust the dosage of Gemcitabine, nab-paclitaxel with or without NPC-1C 
(NEO-102) accordingly.  
 Treatment for each specific toxicity will be administered per standard recommended 
therapy, as appropriate.  
 
3.7 
ON-STUDY EVALUATIONS (SEE STUDY CALENDAR) 
3.7.1 Baseline Evaluation 
 Tumor marker profile: CA19-9. 
 The baseline correlative studies as described in section 5.1.   
3.7.1.1 History and physical exam with vital signs (obtained within 7 days prior to dosing).    
3.7.1.2 Imaging studies (obtained within 28 days prior to dosing):  


32 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 CT scan of chest, abdomen and pelvis  
 MRI if unable to obtain CT scan  
3.7.2 Pre-Dosing Evaluation 
3.7.2.1 Baseline Laboratory Assessment 
Prior to initiation of Day1 Cycle 1 dosing, laboratory evaluation will be performed (if screening 
labs were performed > 72 hours) to include (Results are not required prior to administration of 
first dose (Cycle 1 Day 1 only) of study drug): 
 CBC 
 Urinalysis 
 Electrolytes, BUN, creatinine  
Baseline laboratory values obtained on Day 1 Cycle 1 will not affect the patient’s eligibility to 
participate in the study after the patient has undergone Sponsor approval and been randomized 
and enrolled on the study.  Baseline values will be used to determine dosing procedures for 
Gemcitabine/Abraxane according to Appendix F.  Patients enrolled on Arm A will not receive 
the first dose of NEO-102 until initiation of Gemcitabine/Abraxane therapy. 
3.7.3 Treatment Evaluations 
3.7.3.1 History and physical exam with vital signs and weight on day 1 of each cycle.   
Additional vital signs will be collected as per Section 3.5.1.2. 
A symptom directed physical exam should be performed prior to any dose at the discretion of the 
investigator. 
3.7.3.2 Laboratory evaluation on day 1 [post Cycle 1] (prior to dosing), and day 8* and 15 of 
every cycle (+/- 24 hours) (*will be performed if patient remains on Day 1, 8, and 15 
dosing schedule of chemotherapy): 
 Hematological profile: CBC with differential and platelet count, PT, aPTT, 
fibrinogen. 
 Biochemical profile: electrolytes, BUN, creatinine, AST, ALT, ALP, total bilirubin, 
calcium, phosphorus, albumin, magnesium, uric acid, albumin, and LDH. 
3.7.3.3 Hemoglobin levels within 24-48 hours in Arm A only after the 1st and 2nd dose of NPC-
1C (NEO-102) (Cycle 1, day 2 or 3 and Cycle 1, day 16 or 17) [may be performed by 
local laboratory] 
3.7.3.4 Tumor marker profile: CA19-9 every 2 cycles. 
3.7.3.5 Correlative studies pre cycle 1 and 2 and at the end of the study as described in Section 
5.2.   
3.7.3.6 Imaging studies every 2 cycles 
 CT scan of chest, abdomen and pelvis or MRI if unable to obtain CT scan. 
3.7.3.7 Electrocardiogram (obtained at the visit the subject is taken off-treatment) 
 
 


33 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
3.8 
STUDY CALENDAR 
 
Pre-
Study 
Cycle 1a 
(±2 days) 
 
Cycle 2 
(±2 days) 
 
Cycle 3 (and 
additional 
cycles) 
(±2 days) 
 
Off 
Treatm
ent 
Visit  
At least 
30 (±5) 
days 
after 
the last 
dose of 
study 
agentl 
Day 
 
1 
8 
15 22 
1 
8 
15 22 
1 
8 
15 
 
 
Gemcitabine 
 
X 
X 
X 
R
E
S
T 
X Xm 
X 
R
E
S
T 
X Xm 
X 
 
 
nab-paclitaxel 
 
X 
X 
X 
X Xm 
X 
X Xm 
X 
 
 
NPC-1C(NEO-102)  
(arm A only) 
 
X 
 
X 
X 
 
X 
X 
 
X 
 
 
Premedicationsb 
 
X 
X 
X 
X Xm 
X 
X Xm 
X 
 
 
Informed consent 
IHC Screening 
Protocol Consent 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Adverse event 
evaluation 
 
X 
X 
X 
X Xm 
X 
X Xm 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X Xm 
X 
X Xm 
X 
X 
X 
Physical exam 
X 
X 
Xj 
Xj 
X Xjm 
Xj 
X Xjm 
Xj 
X 
 
Vital signs 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight  
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
Performance Status 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
CBC w/differentialc, 
Platelets 
X 
Xa 
X 
X 
X Xm 
X 
X Xm 
X 
X 
 
PT, PTT, Fibrinogen 
X 
 
Xk 
X 
X 
Xk 
X 
X 
Xk 
X 
X 
 
Serum chemistryd 
X 
Xa 
X 
X 
X Xm 
X 
X Xm 
X 
X 
 
Urinalysis 
 
X 
 
 
 
 
 
 
 
 
 
 
Serum CA19-19 
X 
 
 
 
 
 
 
X 
 
 
 
 
Pregnancy Test (urine or 
serum) 
X 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
Xi 
 
Restaging radiologic 
Evaluatione 
X 
 
 
 
 
 
 
X 
 
 
Xk 
 
IHC staining of tumor 
tissue for NPC-1C 
Xh 
 
 
 
 
 
 
 
 
 
 
 
HACAf 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Immunomonitoringg 
 
X 
 
 
X 
 
 
 
 
 
 
 


34 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
a: Baseline labs (CBC, electrolytes, BUN, creatinine, and urinalysis) will be repeated within 24 hours prior to the first dosing (if 
screening labs > 72 hours)  (results are not required prior to drug administration). See section 3.7.1.  
b: Premedications: dexamethasone 10 mg IV , diphenhydramine 50 mg IV and ranitidine 50mg or equivalent IV 20-30 minutes 
prior to NPC-1C(NEO-102). Antiemetic primary prophylaxis: (preferred agents) Ondansetron 8 mg IV or 16–24 mg po or 
Granisetron 2 mg PO or 1 mg IV for 1 dose. For details please refer to section 3.5.3.1. 
c: Arm A only: Hgb will be drawn within 24-48 hrs after 1st and 2nd dose of NPC-1C (NEO-102) 
d: Electrolytes, BUN, creatinine, AST, ALT, ALP, total bilirubin, calcium, phosphorus, albumin, magnesium, uric acid, albumin, 
and LDH. 
e: CT scan chest, abdomen, pelvis; or MRI if unable to obtain a CT scan. See section 3.7.1. 
f: Arm A only: HACA will be collected at baseline (prior to the first infusion) and at off treatment visit. See section 5.2.2 for 
details. 
g: Arm A only : PBMCs and serum will be analyzed for immunomonitoring from patients prior to first treatment on C1D1 and 
prior to dose on C2D1. It is also optional to perform these analyses 8 weeks after the initiation of the study and in the end of the 
study treatment for patients at NIH only. See section 5.2.3 for details. 
h:  To be performed prior to other screening evaluations after signing IHC Screening Consent.  Only if ≥ 20% will other screening 
evaluations be performed.    
i: If subject is taken off study treatment at this evaluation, obtain an ECG for comparison with baseline.  
j:  A symptom directed physical exam should be performed prior to any dose at the discretion of the investigator: As indicated 
with hemolysis evaluation.  
k: Only if clinically indicated. 
l. Refer to Section 3.9 for Follow up Evaluations 
m If dosing modifications, dose delays or doses are skipped during Cycle 1 due to toxicity attributed to gemcitabine/nab-
paclitaxel, the investigator may decide it is in the patient’s best interest to administer gemcitabine and nab-paclitaxel on a Day 1 
and Day 15 (biweekly) schedule.  In which case assessments will not be necessary on Day 8. The rationale and plan should be 
documented in the medical record and eCRF. 
3.9 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA 
3.9.1 Criteria for removal from protocol therapy 
 Unacceptable adverse event(s) as defined in the dose limiting toxicity section in the 
Phase I part (section 3.3.1) or the following criteria for the Phase IIB part: 
o Grade 4 infusion reaction due to NPC-1C (NEO-102). 
o Grade 4 non-hematologic toxicities due to NPC-1C (NEO-102) or the 
combination therapy.  
o Grade 3 non-hematologic toxicities due to NPC-1C (NEO-102) or the 
combination therapy that does not resolve to ≤ grade 1 within 14 days after 
holding the treatment. 
o Grade 4 hematologic toxicities due to NPC-1C (NEO-102) or the combination 
therapy that does not resolve to ≤ grade 2 after appropriate treatment with 
filgrastim or blood transfusion within 14 days after holding the treatment.  
 Disease progression as determined by clinical evaluation or RECIST criteria (v1.1).   
 Investigator decision: extraordinary medical circumstances: If at any time the constraints 
of this protocol are detrimental to the patient’s health, the patient may be removed from 
the protocol therapy. 
 Patient decides to withdraw from treatment. 
 Intercurrent illness that prevents further administration of study treatment. 


35 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
3.9.2 Off-Study Criteria 
 Voluntary withdrawal of consent to participate in the study or the follow up period. 
 Subject lost to follow up. 
 Death. 
Authorized staff must notify the Sponsor when a subject is taken off-study (please see CRF 
Manual). 
3.10 FOLLOW UP EVALUATIONS 
3.10.1.1 
Patients who discontinue treatment with NPC-1C (NEO-102) and 
Gemcitabine/nab-paclitaxel due to toxicity will undergo disease evaluation every 1-3 
months until the development of progressive disease, at which time they will continue to 
be followed for survival. 
 All study subjects will be followed for overall survival only once active treatment has 
been completed (as indicated above).  
 Patients will be followed until resolution of toxicity to at least Grade 1. This may be done 
by phone if appropriate.  Patients must be evaluated for toxicity at least 30 days after the 
last dose of study agent for toxicity. 
 Follow-up will be quarterly assessment of survival status. Every attempt will be made to 
contact patient/subject including: contacting referring physician, contacting emergency 
contact patient identified on admission, checking SSDI (Social Security Death Index) or 
Ancestry.com. 
 Blood drawn for correlative studies during follow up visits as indicated in Section 5.2. 
4 CONCOMITANT MEDICATIONS/MEASURES 
4.1 
PERMITTED CONCOMITANT MEDICATIONS  
Permitted medications will include analgesics (opioid and non-opioid), antiemetics, 
antidiarrheals, pancreatic enzymes, probiotics, multivitamins, adjuvant analgesics, if for the 
purpose of co-analgesia.  Permitted supplements are omega 3 fatty acids and HMB (ß-hydroxy ß-
methylbutyrate) Juven®, and any nutrient-dense medical food supplement, such as ProSure® or 
Ensure® or BOOST®, if taken for at least one month before entering the study.   
Concomitant medications for other medical conditions are permitted as clinically indicated, 
subject to specific protocol requirements outlined in this study. 
4.2 
CONCOMITANT MEDICATIONS NOT PERMITTED  
The following medications are not permitted: Human growth hormone, anabolic steroids, 
cyproheptadine (Periactin®) and supplements other than those mentioned above are not to be 
used during any phase of the study.  So called “off label” or adjuvant medications for malaise, 


36 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
fatigue, anorexia/cachexia are not to be added. No alternative or complementary medicine 
products with purported appetite stimulating effects are permitted.  In addition the following are 
also excluded: 
 Any investigational agent other than NPC-1C (NEO-102). 
 Any elective major surgical procedure deemed not lifesaving. 
 Supplements not specifically permitted (above). 
Should the investigator feel that it is in the patient’s best interests to receive one of the above-
mentioned therapies, the patient must be withdrawn from the study, unless permission to remain 
has been granted in writing by the Sponsor and IRB. 
5 BIOSPECIMEN COLLECTION 
5.1 
IMMUNOHISTOCHEMISTRY WITH NPC-1C:  
IHC with NPC-1C may be performed by the study site or at UT Southwestern Medical Center.  If 
sending slides to UTSW: four (4) unstained slides (5-6 micron thickness) or tissue block will be 
sent to UT Southwestern Medical Center, Dr. Jose Torrealba and Gloria Daniels for IHC staining 
with NPC-1C and interpretation after subject has signed the NPC-1C screening consent using the 
request form in Appendix C, to:   
Dr. Jose Torrealba and Gloria Daniels 
 
 
 
Clements University Hospital 
 
6201 Harry Hines Blvd.  4th Floor Room 04.246 
Dallas, TX 75390-9234 
Phone: 214-633-6342  
email:  Jose.Torrealba@UTSouthwestern.edu; Gloria.Daniel@UTSouthwestern.edu 
The samples must be accompanied by a completed request form (sample form in Appendix C).  
Results can be expected within 5 business days of receipt of the tissue and completed IHC Request 
form at UT Southwestern Medical Center. 
 
 
 


37 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
5.1.1 Summary of Assay: 
This assay employs a direct immunohistochemical technique using a Biotin Labeled detection 
system (Roche Diagnostics Cat. #11418165001).  The method is summarized in Figure 3:
 
Figure 3: Immunohistochemistry with NPC-1C 
 
5.1.2 Procedure for slide submission 
Site personnel will complete the header on the NPC-1C Immunohistochemical Staining Request 
form (See Appendix C), and complete the information for the return of the results of the IHC 
testing. 
Slides or unstained tissue block will be sent with the completed form in bubble envelopes 
supplied by the Sponsor to the address above.  
5.2 
CORRELATIVE STUDIES FOR RESEARCH 
5.2.1 Blood Collection and Processing: 
A maximum of 116 mL of blood are mandatory samples for collection from each subject in Arm 
A as described in Appendix E.  These samples are processed, shipped according to instructions 
in the Laboratory Manual, and frozen for later analysis. Date and exact time of each blood draw 
should be recorded on the blood tubes.  After processing as outlined in the Laboratory Manual 
samples will be shipped to NCI for immunomonitoring or will be stored as described in detail in 
the Laboratory Manual.  A summary is as follows: 


38 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 Arm A Only: Serum aliquots for HACA are to be stored at -70C or colder until shipped 
to sponsor, as instructed in the Laboratory Manual. Cryovials containing serum aliquots 
from each time-point should be placed into a pre-labeled gridded cardboard storage box 
supplied by the sponsor. 
 Arm A Only: Serum aliquots for cytokines are to be centrifuged and shipped as described 
in the Laboratory Manual until ready to be tested. 
5.2.2 Immunogenicity Testing (HACA) for Arm A only (to be performed at Precision Biologics, 
Inc): 
 Peripheral blood will be collected from all subjects in Arm A only in a red top tube to 
assess immunogenicity (Human Anti-chimeric Antibodies/HACA) as described in 
Appendix E. Immunogenicity studies (HACA) will be collected at baseline (prior to the 
first infusion) and at off treatment visit. A commercially available qualified ELISA assay 
will be used at BioReliance Corp to measure HACA responses against NPC-1C(NEO-102) 
in the serum of subjects.  
 At the time of shipping, transfer equal numbers of cryovial aliquots from each time-point 
to each of the pre-labeled gridded cardboard storage box supplied by the sponsor. 
 Samples will be shipped in subject batches after all samples for the subject have been 
collected and processed. Sponsor will make contact with the site and initiate the shipping 
process. 
 The blood processing and inventory logs should be partially completed after samples were 
processed to serum. At the time of shipping, the remaining sections of the logs should be 
completed. These forms are displayed in the Laboratory Manual provided to each site. 
 All shipments should be on dry ice and via FedEx overnight, using the sponsor’s FedEx 
account number according to instructions in the Laboratory Manual. 
 Do not ship on Fridays or the day before holidays. 
5.2.3 Immunomonitoring of samples (Arm A only; to be performed at NCI): 
Non-immune based therapies have been shown to have significant effects on tumor-specific 
immune responses. There is increasing evidence demonstrating that under certain circumstances 
chemotherapy might have potential beneficiary effects on tumor specific immune responses.  
Both PBMCs and serum will be analyzed for immunomonitoring from patients in Arm A prior to 
first treatment and 4 weeks after initiation (C2D1).  It is also optional to perform this analysis 8 
weeks after the initiation of the study and at the end of treatment for patients at NIH, at the PI 
discretion.  
Frequency, phenotype and function of different immune cells (including CD8+ T cells, CD4+ T    
cells, Tregs and MDSCs) will be analyzed in Dr. Greten’s laboratory at NCI, phone 301-451-4723.  
In addition, approximately 10 ml of each patient blood sample will be transported from CCR, NCI 
by courier to the Clinical Services Program, SAIC-Frederick on the NCI-Frederick campus for 


39 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
future analysis for the ELISPOT assays. These assays will be conducted at the Kopp’s lab: SAIC-
Frederick, Phone: 301-846-1707. Please follow the instructions in Table 5 for the specific amount 
of blood samples and tubes. 
5.2.3.1 Immune response to mesothelin by ELISPOT: 
Mesothelin is a tumor differentiation antigen that is highly expressed in pancreatic cancer. 
Mesothelin expression by immunohistochemistry is present in approximately 100% of ductal 
pancreatic adenocarcinomas, which makes it an attractive target to test for immune response. 
Accordingly, this study will investigate the effect of the treatment of NPC-1C(NEO-102), nab-
paclitaxel and Gemcitabine on the patient’s immune response to Mesothelin tested by ELISPOT 
at baseline, post cycle 1, post cycle 2 (optional). 
5.2.3.2 CD4, CD8 and regulatory (CD4+ CD25high) T-cell:  
Regulatory T cells have been shown to inhibit the activation and function of T cells that participate 
in antigen-specific immune responses. Higher levels of Tregs have been reported in the PBMCs 
of patients with several types of tumors. The number and phenotype of T-cells in PBMCs from 
patients in this study will be determined by flow cytometry analysis. Approximately 100,000 cells 
will be re-suspended in staining buffer (phosphate-buffered saline containing 3% fetal bovine 
serum) and stained for CD4, CD8, CD25, and FoxP3. The ratios between Tregs and CD4 Effector 
cells and the ratios between Tregs and CD8 Effector cells will also be analyzed.    
5.2.3.3 Myeloid-derived suppressor cells (MDSCs):  
MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known 
about these cells in humans. Human MDSCs have been described in patients with many tumors 
including pancreatic cancer. This study will investigate the effect of the treatment of NPC-
1C(NEO-102), nab-paclitaxel and Gemcitabine on the Myeloid derived suppressor cells in patients 
with pancreatic cancer.  7-Flow cytometry will performed by LSRII FACS or similar technology 
with FlowJo (or similar software) analysis. 
5.2.2.4 Cytokines: Cytokines will be measured in each patient serum including: INFα, INFγ, IL-
4, and GM-CSF.    
5.2.4 Summary of correlative studies 
The laboratories performing the testing, sample time points, blood volumes and tube 
requirements are specified in Appendix E.   
Directions for handling and shipping of research blood samples from patients in Arm A enrolled 
at participating sites for analysis at NCI is described in detail in the Laboratory Manual. 
5.3 
SAMPLE STORAGE, TRACKING AND DISPOSITION 
All specimens obtained in the protocol are used as defined in this protocol. Any specimens that 
are remaining at the completion of the protocol will be destroyed or moved to a tissue study as 
described below. The study will remain open so long as sample or data analysis continues. 
Samples from consenting subjects will be stored until they are no longer of scientific value or if a 
subject withdraws consent for their continued use. If a patient withdraws consent the 


40 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
participant’s data will be excluded from future distributions, but data/samples that have already 
been distributed for approved research use will not be able to be retrieved. The PI will report any 
loss or destruction of samples to the institutional IRB as soon as he/she is made aware of such 
loss.  Samples will also be reported as lost if they are lost in transit between facilities or 
misplaced by a researcher.  Freezer problems, lost samples or other problems associated with 
samples will also be reported according to the institutions’ policies and procedures. 
 
Samples collected during the course of this study will not be sent with personal identifiers, but will 
include the patient’s study number, date and time of sample acquisition.  Blood processing, sample 
labeling, and collection for immunologic studies will be conducted as outlined in the study Section 
5.2.  Samples will be tracked and considered the responsibility of the principal investigator. Tissue 
samples sent to UT Southwestern Medical Center for IHC screening of NPC-1C antibody/antigen 
target with unique study identification number as assigned by the study team as per Appendix C 
for medical record tracking at the testing site. 
 
All cryopreserved samples are tracked for freezer location and storage criteria. All samples are 
stored in monitored freezers/refrigerators either in the freezers at Precision Biologics, Inc. or 
designee, or the investigator’s laboratory, at specified temperatures with alarm systems in place. 
All samples (blood or tissue) are documented in a secure computer database with identification 
and storage location, with computer backup according to established standards.  Samples 
submitted to Precision Biologics, Inc. are tracked on hard copy case report forms in locked files 
with access to designated sponsor personnel. 
 
At the termination of this protocol, if additional studies are to be performed on any samples 
retaining subject identifiers, obtained during the conduct of this trial, a Request to Conduct 
Research for Stored Human Samples Specimens, or Data Collected in a Terminated NCI-IRB 
Protocol will be submitted. Any new uses of samples collected during the course of this trial must 
be reviewed and approved by the participating site’s IRB.  
6 DATA COLLECTION AND EVALUATION  
6.1 
DATA COLLECTION 
Data will be collected, entered onto either paper Case Report Forms or via electronic data 
capture (EDC) [Axiom’s Go Cubed Clinical Trial Suite] provided by the sponsor, and monitored 
according to Section 7.4.  All data will be kept secure. Personal identifiers will not be used when 
collecting and storing data. An enrollment log will be maintained in the regulatory binder/file 
which is the only location of personal identifiers with unique subject identification number. 
The investigators at each site will be responsible for the collection, maintenance and quality 
control of the study data.  Data will be prospectively collected and recorded on r CRFs by each 
sites’ personnel responsible for study data.  Toxicity and treatment data will be entered onto 
study CRFs within at least 2 weeks of each patient encounter. 


41 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
6.2 
RESPONSE CRITERIA 
For the purposes of this study, patients should be re-evaluated for response every 8 weeks of the 
treatment (two cycles of therapy, 6 doses of Gemcitabine/nab-paclitaxel and 4 doses of NPC-1C 
(NEO-102)).  In addition to a baseline scan, confirmatory scans should also be obtained at least 4 
weeks following initial documentation of objective response. 
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) [Eur J Ca 45:228-247, 2009].  Changes in the largest diameter (unidimensional 
measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph 
nodes are used in the RECIST criteria. 
6.2.1 Definitions 
Evaluable for toxicity:  All patients will be evaluable for toxicity from the time of their first 
treatment with Gemcitabine/nab-paclitaxel with or without NPC-1C (NEO-102).   
Evaluable for objective response: Only those patients who have measurable disease present at 
baseline, 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.) 
6.2.2 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 2 mm).  At baseline and in follow-up, only the short axis will 
be measured and followed. 
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. 


42 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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Protocol Edition 13 
Rev.7/19/2016 
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.  
6.2.3 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.  
CT - is the best currently available and reproducible methods to measure target lesions selected 
for response assessment. For this study helical Multi-detector CT will be performed with cuts of 
5 mm in slice thickness for chest, abdomen and pelvis lesions and 2-3 mm thickness for head and 
neck lesions. 
6.2.4 Response Criteria 
6.2.4.1 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). 


43 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
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. 
6.2.4.2 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 of tumor 
marker level above the normal limits. 
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). 
6.2.4.3 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 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
>4 wks. 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 
wks. from baseline** 
PD 
Any 
Yes or 
No 
PD 
no prior SD, PR or CR 


44 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Any 
PD*** 
Yes or 
No 
PD 
Any 
Any 
Yes 
PD 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** 
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. 
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
 
 
 
 
 
6.2.5 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.  
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 


45 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
6.2.6 Progression-Free Survival (PFS) 
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first. 
6.2.7 Overall Survival (OS) 
Overall survival is defined as the duration of time from start of treatment to time of death. 
6.3 
TOXICITY CRITERIA 
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
4.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40).  
6.3.1 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. 
7 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY 
MONITORING PLAN 
7.1 
DEFINITIONS 
7.1.1 Adverse Event 
An adverse event is defined as any reaction, side effect, or untoward event that occurs during the 
course of the clinical trial associated with the use of a drug in humans, whether or not the event 
is considered related to the treatment or clinically significant. For this study, AEs will include 
events reported by the patient, as well as clinically significant abnormal findings on physical 
examination or laboratory evaluation. A new illness, symptom, sign or clinically significant 
laboratory abnormality or worsening of a pre-existing condition or abnormality is considered an 
AE.  All AEs must be recorded on the AE case report form. 
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until satisfactory resolution. AEs starting from the first dose of drug 
(Gemcitabine, abraxane, NEO-102) up to 30 days following the last dose of study drug should be 
recorded in the Axiom electronic database.   


46 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following: 
 
Results in discontinuation from the study 
 
Is associated with clinical signs or symptoms  
 
Requires treatment or any other therapeutic intervention 
 
Is associated with death or another serious adverse event, including hospitalization.  
 
Is judged by the Investigator to be of significant clinical impact 
 
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 
7.1.2 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the investigator brochure or is not listed at the specificity or severity that has been observed; or, 
if an investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. 
"Unexpected”, also refers to adverse events or suspected adverse reactions that are mentioned in 
the investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
7.1.3 Serious  
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others. 
7.1.4 Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
 
Death, 
 
A life-threatening adverse drug experience 
 
Inpatient hospitalization or prolongation of existing hospitalization 
 
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 
A congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate 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. 
7.1.5 Disability 


47 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
A substantial disruption of a person’s ability to conduct normal life functions. 
7.1.6 Life-threatening adverse drug experience 
Any adverse event or suspected adverse reaction that places the patient or subject, in the view of 
the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused death. 
7.1.7 Protocol Deviation (NIH Definition) 
Any change, divergence, or departure from the IRB approved research protocol. To 
accommodate changes for patient schedules, holidays and unforeseen weather incidences, any 
change or divergence in the scheduling or conduct of the examinations, tests, scans or treatment 
described in this protocol will not be considered a protocol deviation if performed +/- 2 days of 
the scheduled time point.. 
7.1.8 Non-compliance (NIH Definition) 
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects. 
7.1.9 Unanticipated Problem 
Any incident, experience, or outcome that: 
  Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
 Is related or possibly related to participation in the research; AND 
 Places subjects or others at a greater risk of harm (including physical, psychological, 
economic, or social harm) than was previously known or recognized. 
7.2 
REPORTING CRITERIA TO THE SPONSOR  
7.2.1 Reporting to the Sponsor 
An investigator must immediately report to the sponsor (Precision Biologics, Inc.) any 
unanticipated problem, serious adverse event, dose limiting toxicity, related unexpected events, or 
any instance of hemolysis, whether or not considered drug related occurring from the time of on-
study to 30 days after the last dose of study treatment, including those listed in the protocol or 
investigator brochure and must include an assessment of whether there is a reasonable possibility 
that the study drug caused the event.  A report will be submitted via electronic data capture (EDC) 
[Axiom’s Go Cubed Clinical Trial Suite] with supporting documentation e-mailed or faxed  to the 
sponsor within one week (7 calendar days) of the Investigator becoming aware of the event.  An 


48 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
investigator must also report to the sponsor any deviation or changes from the protocol regimen 
without prior agreement by the sponsor and prior review and documented approval by the 
institution’s IRB, except where necessary to eliminate an immediate hazard to trial subjects, or 
when the change(s) involve only logistical or administrative aspects of the trial (e.g. change of 
telephone numbers). 
Deviations, Unanticipated problems, SAEs, DLTs, related unexpected events, instances of 
hemolysis should be reported via electronic data capture (EDC) [Axiom’s Go Cubed Clinical Trial 
Suite] with supporting documentation sent to:  
Phil Arlen, MD, Medical Sponsor 
e-mail: parlen@Precision-Biologics.com  
Tel: (301) 728-4883 
FAX: (240-669-9828) 
Cc: kcui@Precision-Biologics.com;azaki@Precision-Biologics.com; smavroukakis@Precision-
Biologics.com 
 
Study endpoints that are serious adverse events (e.g. all-cause mortality) must be reported in 
accordance with the protocol unless there is evidence suggesting a causal relationship between the 
drug and the event (e.g. death from anaphylaxis).  In that case, the investigator must immediately 
report the death to the sponsor. 
The sponsor shall promptly investigate all safety information received and report follow up 
information in an IND safety report as soon  
as relevant information is available.  If the results of the sponsor’s investigation show that an 
adverse event not initially determined to be reportable is later identified as reportable, the sponsor 
shall report such experience in a written safety report as soon as possible, but in no event later than 
15 calendar days after the determination is made. 
Planned hospital admissions or surgical procedures for an illness or disease which existed before 
the subject was enrolled in the trial or before study drug was given, are NOT to be considered AEs 
unless they occur at a time other than the planned date. 
7.2.1.1 Adverse Event Recording 
Adverse events, both serious and non-serious, and deaths will be captured from the first dose of 
study drug up to and including 30 days after the last dose of study drug.  All serious adverse 
events will be monitored until they are resolved or are clearly determined to be due to patient’s 
stable or chronic condition or intercurrent illness(es).  Any adverse event that occurs at any time 
after completion of 30 days after the last dose of study drug, that the investigator considered to 
be related to study medication, should be reported to the sponsor. 
For all serious and non-serious adverse events, the investigator must determine both the intensity 
of the event and the relationship of the event to study drug administration. 
Intensity for each adverse event will be determined by using the National Cancer Institute 
Common Terminology Criteria for Adverse Events v4.0 (CTCAE) as a guideline, wherever 


49 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
possible.  In those cases where the CTCAE criteria do not apply, intensity should be defined 
according to the following criteria: 
Mild  
Grade 1, asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Moderate  
Grade minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL. 
Severe 
Grade 3 Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization indicated; 
disabling; limiting self care ADL. 
Life-threatening 
Grade 4, Life-threatening consequences; urgent intervention indicated. 
Death 
Grade 5 Death related to AE.  
 
Relationship to study drug administration will be determined and recorded as follows: 
Unrelated  
The AE is clearly NOT related to the study drug, no temporal relationship 
exists, and can be attributed to alternative cause(s). 
Unlikely  
The current state of knowledge about the drug and the patient’s disease 
indicates that a relationship is unlikely. 
Possibly  
A reaction that follows a plausible temporal sequence from administration 
of the study drug and follows a known response pattern to the suspected 
study drug. The reaction might have been produced by the patient’s 
clinical state or other modes of therapy administered to the patient. 
Probably  
A reaction that follows a plausible temporal sequence from administration 
of the study drug and follows a known response pattern to the suspected 
study drug. The reaction cannot be reasonably explained by the known 
characteristics of the patient’s clinical state or other modes of therapy 
administered to the patient. 
Definitely  
An adverse event that is clearly related to the study drug with temporal 
relationship to the administration of the study drug, follows a known 
pattern of response and no alternative causes. 
7.3 
IND SAFETY REPORTS 
The sponsor shall be responsible for notifying all participating investigators and the FDA in a 
written IND safety report of: 
1) Any adverse experience associated with the use of the drug that is both serious and 
unexpected; or 
2) Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity. 


50 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Each notification will be made as soon possible and in no event later than 15 calendar days after 
the sponsor’s initial receipt of the information.   
In each written IND safety report, all safety reports previously filed with the IND concerning a 
similar adverse experience will be noted, and the significance of the adverse experience will be 
analyzed in light of the previous, similar reports. 
- 
Telephone and facsimile transmission safety reports. The sponsor shall also notify 
FDA by telephone or by facsimile transmission of any unexpected fatal or life-
threatening experience associated with the use of the drug as soon as possible but in 
no event later than 7 calendar days after the sponsor's initial receipt of the information. 
- 
Reporting format or frequency. FDA may request a sponsor to submit IND safety 
reports in a format or at a frequency different than that required under this paragraph. 
The sponsor may also propose and adopt a different reporting format or frequency if 
the change is agreed to in advance by the director of the new drug review division in 
the Center for Drug Evaluation and Research responsible for review of the IND. 
7.4 
DATA AND SAFETY MONITORING PLAN 
7.4.1 Principal Investigator/Research Team  
The clinical research team will meet on a regular basis when patients are being actively treated on 
the trial to discuss each patient. Decisions about dose level enrollment and dose escalation if 
applicable will be made by the sponsor based on the toxicity data from prior patients at all 
participating sites.  Individual investigators shall not proceed to treat a new subject until they have 
received sponsor approval and dose assignment as outlined in Appendix B. 
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Adverse events will be reported as required by the investigator’s 
institutional policies and procedures. Any safety concerns, new information that might affect either 
the ethical and or scientific conduct of the trial, or protocol deviations and violations will be 
immediately reported to the investigator’s IRB and to the Sponsor.  
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 
research staff.  
7.4.2 Administrative Sponsor Requirements 
7.4.2.1 Sponsor Study monitoring 
The Sponsor will review all serious adverse events and will monitor the data and toxicities to 
identify trends at least weekly during treatment of subjects.  The participating sites’ PI(s) and the 
coordinating sponsor will discuss all toxicities experienced after the first 6 subjects have been 
treated in in Arm A to collaboratively determine proceeding with enrollment.  In the event of a 
DLT, the participating site PIs will be notified within 24 hours of the nature of the event.  The 
coordinating sponsor will be responsible for revising the protocol as needed to maintain safety. 


51 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Monitoring and auditing procedures implemented by Precision Biologics, Inc. or its designee will 
be followed in order to comply with GCP guidelines.  On-site checking of case report forms for 
completeness and clarity and consistency as compared with source documents, and clarification of 
administrative matters will be performed. 
The study will be monitored by Precision Biologics, Inc. or its designee on a regular basis 
throughout the study period.  Monitoring will be done by personal visits from a representative of 
the sponsor (site monitor) who will review the source documents.  Source documentation includes 
but is not limited to the subject’s clinic and/or office chart, hospital chart, informed consent forms, 
treatment notes, laboratory reports, pharmacy records, radiographs, and any other records 
maintained to conduct and evaluate the clinical study.  The investigator must ensure the accuracy 
and completeness of the data reported, and its consistency with the source documentation.  The 
primary source document for this study will be the subject’s medical records.  If separate research 
records are maintained by the investigator(s) both the medical record and the research records will 
be monitored/audited for the purposes of the study.  The site monitor will ensure that the 
investigation is conducted according to protocol design and regulatory requirements by frequent 
communications (letter, telephone, and fax). 
All unused study drug and other study materials are to be returned to Precision Biologics, Inc. after 
the clinical phase of the study has been completed. 
7.4.2.2 On-site audits 
Regulatory authorities, the IEC/IRB, and/or Precision Biologics’s clinical quality assurance group 
may request access to all source documents, printouts of any data entry forms, and other study 
documentation for on-site audit or inspection.  Direct access to these documents must be 
guaranteed by the Investigator, who must provide support at all times for these activities. 
7.4.2.3 Data entry completion 
For subjects who provide informed consent and were not entered/randomized into the study, the 
reason the subject was not entered/randomized, i.e., did not meet one or more inclusion criteria, 
met one or more exclusion criteria, or other (e.g., lost to follow up, consent withdrawn), will also 
be collected and maintained on the Screening/Study Log. 
It is the Investigator’s responsibility to ensure the accuracy, completeness, and timeliness of the 
data reported for each subject.  Source documentation supporting the data should indicate the 
subject’s participation in the study and should document the dates and details of study procedures, 
adverse events, and patient status.   
The Investigator, or designated representative, should complete the data entry as soon as possible 
after information is collected, preferably within 2 weeks of study visit.  Any outstanding entries 
must be completed immediately after the final examination.  An explanation should be given for 
all missing data. 
The Investigator's Study File will contain documents as outlined in ICH ECP E6 Section 8, 
including the protocol/amendments, Data Query Forms, Institutional Review Board and 
governmental approval with correspondence, sample informed consent, sponsor correspondence 


52 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
records, 
staff 
curriculum 
vitae 
and 
authorization 
forms 
and 
other 
appropriate 
documents/correspondence, etc. 
7.5 
DRUG ACCOUNTABILITY 
Accountability for the study drug at the study center is the responsibility of the Investigator.  The 
Investigator will ensure that the study drug is used only in accordance with this protocol.  Where 
allowed by site SOPs, the Investigator may choose to assign some of the drug accountability 
responsibilities to a pharmacist or other appropriate individual.  Drug accountability records 
indicating the drug’s delivery date to the center, inventory at the center, use by each subject, and 
return to Precision Biologics (or disposal of the drug, if approved by Precision Biologics) will be 
maintained by the participating site.  These records will adequately document that the subjects 
were provided the doses as specified in the protocol and should reconcile all study drug received 
from Precision Biologics.  Accountability records will include dates, quantities, batch/serial 
numbers, expiration dates (if applicable), and patient numbers.  The sponsor or its designee will 
review drug accountability at the site on an ongoing basis during monitoring visits. 
All unused study drug will be retained at the site until inventoried by the monitor.  All unused or 
expired study drug will be returned to Precision Biologics or if authorized, disposed of at the study 
site as hazardous waste in accordance with governing regulations. 
7.5.1.1 Premature closure of the study 
This study may be prematurely terminated, if in the opinion of Precision Biologics, there is 
sufficient reasonable cause.  The Investigator may terminate his/her participation for reasonable 
cause.  The terminating party must provide written notification documenting the reason for study 
termination.   
Circumstances that may warrant termination include, but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to subjects; 
 Failure to enter subjects at an acceptable rate; 
 Insufficient adherence to protocol requirements; 
 Insufficient and/or inadequate evaluable data; or 
 Plans to modify, suspend or discontinue the development of the study drug. 
8 STATISTICAL SECTION   
The primary objective of this phase 2.5 study is to determine if the combination of NPC-1C and 
gemcitabine plus nab-paclitaxel is potentially able to improve the overall survival for patients 
who have pancreatic cancer over gemcitabine plus abraxane alone. The trial will be conducted as 
a 2-arm randomized multi-institution trial of NPC-1C plus gemcitabine and nab-paclitaxel vs. 
gemcitabine and nab-paclitaxel. Since a phase 2.5 trial is meant to identify a trend in a 
randomized, controlled fashion, any suggestion of positive findings will be evaluated for the 
potential to conduct a larger, subsequent multi-institutional definitive trial through an established 
cooperative group mechanism. 


53 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
Based upon results in the literature, patients who would be eligible to be randomized on this trial 
would be expected to have an estimated 4.5 to 4.8 month median survival with gemcitabine 
alone, but this may be enhanced somewhat with the addition of nab-paclitaxel. The goal of this 
study will be to determine if the use of NPC-1C along with gemcitabine and nab-paclitaxel will 
result in patients having an increased median survival of 8 months vs. an estimated 5 months 
without NPC-1C.  Kaplan-Meier curves and a two-tailed log-rank test will be the primary 
analysis methods. Assuming exponential survival curves, the hazard rate for gemcitabine plus 
nab-paclitaxel would be estimated to be 0.1386, or approximately a 14% probability of dying 
each month when the median survival time is 5 months.  If we assume that the arm with NPC-1C 
will be associated with a median survival of 8 months, this corresponds to a hazard rate of 
0.0866 and the resulting hazard ratio for the comparison of the two overall actuarial curves 
would be 1.60. Following the principals of a phase 2.5 design, to compare these curves and 
detect a difference with a 0.10 one-tailed log-rank test, a total of 45 evaluable subjects per arm 
(90 total) will need to be randomized over a thirty month period and a maximum follow-up of 42 
months (12 months after the last patient has enrolled), with occurrence of 82 total deaths on both 
arms, in order to have 80% power to compare the curves.  
The trial will be monitored by the NCI/CCR DSMB for toxicity on an annual basis, and will also 
perform one planned interim analysis for futility and for efficacy at a midpoint in the trial. The 
initial evaluation for safety of the combination will take place after treatment of the first 6 
patients in Arm A. If ≥2 of the first 6 patients on Arm A experience either of the toxicities listed 
in Section 3.3.1.1, the study will be paused pending modification discussions with the IRB and 
FDA.  
The first overall evaluation for toxicity will take place at the first annual DSMB meeting after 10 
patients have been enrolled and treated on each arm. The goal will be to confirm that the toxicity 
among the two arms is not significantly different. If the NPC-1C arm exhibits a significantly 
greater fraction of patients experiencing a grade 3 or higher toxicity than the other arm, whether 
based on a specific toxicity or any toxicity, then the trial will be closed to further accrual until an 
amendment can be made to lessen the toxic effects of NPC-1C. 
A single evaluation for futility will also be undertaken to permit the trial to stop accrual in the 
event that there is very low probability of detecting an advantage to using NPC-1C. At the first 
annual DSMB meeting taking place after 23 evaluable patients have been enrolled on each arm 
and potentially followed for at least 6 months, if the hazard ratio for survival comparing the two 
arms exceeds 1.00, and is favoring the arm without NPC-1C, then the trial will no longer enroll 
any other patients as it would be unlikely to be able to demonstrate a gain in survival compared 
to the arm without NPC-1C.  
A single evaluation for efficacy will also be performed at the first annual DSMB meeting held 
after approximately 23 patients have been enrolled on each arm and followed for 6 months. 
Should the p-value for the comparison of the two arms be <0.005, then the DSMB should 
recommend that the trial will be closed for the presence of early, strong efficacy benefit for the 
arm with NPC-1C. 


54 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
It is expected that all 90 patients can be accrued onto this trial in thirty months. In order to allow 
for a very small number of inevaluable patients, the accrual ceiling will be set at 94 patients. 
9 MULTI-INSTITUTAL GUIDELINES 
9.1 
COLLABORATIVE AGREEMENT   
The investigational study agent (NPC-1C (NEO-102)) is provided by Precision Biologics, Inc. to 
participating sites under a negotiated research agreement.  
Participating sites agree to conduct the Clinical Trial in accordance with applicable provisions of 
ICH E6 (R1): FDA Good Clinical Practice and they agree to comply with all applicable U.S., state 
and local laws, regulations and guidelines. 
The sponsor (or designee) will be responsible monitoring and quality assurance of all data at 
participating sites in accordance with the clinical monitoring plan.  Monitoring will be done in 
compliance with current FDA Good Clinical Practice Guidelines (E6 (R1) and the sponsor will 
communicate any clinically significant findings from clinical monitors to the participating sites in 
a timely manner. 
The sponsor will provide the participating sites with current copy of the Investigator’s Brochure 
for the investigational agent and any later revisions and addenda to the IB during the course of the 
study. 
The sponsor will assume responsibility for any alteration in or amendment to the protocol, which will 
undergo review by the participating sites.  Prior to such alteration or amendment becoming effective they 
must be approved in writing by the relevant participating sites IRB(s) and submitted to the FDA.  
The sponsor will be responsible for the data, and scientific reporting of all results/data obtained 
from the Clinical Trial will be a collaborative effort with the investigators of the participating sites.  
All publications based on the results of the clinical trial must be reviewed and approved by the 
sponsor prior to submission for publication. 
9.2 
IRB APPROVALS, AMENDMENTS AND CONSENTS: 
Participating institutions will provide the Sponsor with copies of the initial local IRB approvals 
and semi-annual or annual continuing review approvals. Registration will be halted at any 
participating institution in which a current continuing approval is not on file with the Sponsor. 
Only one version of the protocol will be the correct version; amendments must be initiated upon 
receipt from the Sponsor. Each site will be responsible for its own IRB submissions. 
9.3 
PATIENT REGISTRATION: 
All participating institutions must register patients with the sponsor as specified under section 2.3. 
Such patients will be treated, monitored, and managed according to the guidelines of this protocol, 
after signing a current version of the informed consent.  


55 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
9.4 
DRUG DISTRIBUTION: 
Site PI’s or their designees will order the study drug (NPC-1C(NEO-102)) from Precision 
Biologics, Inc. by completing and sending by fax or e-mail the Clinical Drug Request. The drug 
will be shipped to the pharmacy for each institution. Contact information: Precision Biologics, 
Inc., Phone: (301) 728-4883 (cell), FAX: 240-428-1552, e-mail: parlen@Precision-Biologics.com; 
azaki@ Precision-Biologics.com; kcui@Precision-Biologics.com; smavroukakis Precision-
Biologics.com. 
9.5 
DATA COLLECTION AND TOXICITY REPORTING: 
This protocol will be conducted as a single research effort and data from each participating site 
will be included in the analysis of results.  All patients must meet eligibility requirements as 
demonstrated on the protocol’s Eligibility Checklist (Appendix B) and all patients must sign an 
Informed Consent before entering the study.  All toxicity and event data must be documented and 
transcribed on the Case Report Forms supplied by the Sponsor to the participating institutions, 
within two weeks of each patient’s visit.  In addition, complete records will be maintained on each 
patient at the participating institutions.  These will consist of hospital records with any 
supplementary information obtained from outside laboratories, radiology reports or physicians’ 
records.  These records will serve as the primary source of material that forms the basis for the 
research record.   All data collection forms and records will be audited on-site at participating 
institutions and should be made available at the time of the study audit.  Reportable Serious 
Adverse Events (SAE) and reporting requirements are defined in Section 7.  All reportable SAEs 
must be reported by the participating centers directly to the institution’s IRB according to the 
relevant IRB requirements, and to the trial sponsor as specified in Section 7 IND Sponsor 
Reporting Criteria. 
10 HUMAN SUBJECTS PROTECTIONS  
10.1 RATIONALE FOR SUBJECT SELECTION 
Subjects of both genders and from all racial and ethnic groups are eligible for this trial if they meet 
the eligibility criteria. No groups are being excluded from participation in the trial. Efforts will be 
made to extend the accrual to a representative population. 
10.2 PARTICIPATION OF CHILDREN 
Individuals under the age of 18 will not be eligible to participate in this study because they are 
unlikely to have pancreatic cancer, and because of unknown toxicities in pediatric patients. 
10.3 EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS 
Patients will receive evaluation of their disease at the participating site. This protocol may or may 
not benefit an individual, but the results may help the investigators learn more about the disease 
and develop new treatments for patients with this disease. Benefit cannot be promised nor can the 
chance of benefit be accurately predicted. All care will be taken to minimize side effects, but they 
can be unpredictable in nature and severity. This study may involve risks to patients, which are 


56 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
currently unforeseeable. Patients will be examined and evaluated prior to enrollment. All 
evaluations to monitor the treatment of patients will be recorded in the patient chart. If patients 
suffer any physical injury as a result of the participation in this study, immediate medical treatment 
is available at the participating sites. Although no compensation is available, any injury will be 
evaluated and treated in keeping with the benefits or care to which patients are entitled under 
applicable regulations. 
In all publications and presentations resulting from this trial, patients’ anonymity will be protected 
to the maximum extent possible. Authorized personnel from the National Cancer Institute (NCI), 
the Sponsor, and Food and Drug Administration (FDA) or other regulatory authorities may have 
access to research files in order to verify that patients’ rights have been safeguarded. 
10.4 CONSENT AND ASSENT PROCESS AND DOCUMENTATION 
The investigational nature and research objectives of this trial, the procedures and treatments 
involved and their attendant risks, discomforts, benefits, and potential alternative therapies will be 
carefully explained to the patient.  
10.4.1 IHC Screening Consent 
Consent must be obtained prior to obtaining and analyzing tissue samples (2 or more unstained 
slides or tissue block).  Telephone consent may be employed in order to screen outside samples, 
according to institutional/IRB procedures.  In such cases, a protocol investigator will review the 
Screening Sample Consent form by telephone.  The consent signatures will be witnessed and a 
copy will be faxed to the investigator’s site and the original sent by mail to the PI.  Prospective 
subjects who consent to sample testing will be documented on the IHC Screening Log Sheet. 
10.4.2 Study Screening Informed Consent 
A signed informed consent document will be obtained by a study investigator prior to entry onto 
the study. The PI or associate investigator will meet with the patient to discuss the protocol 
treatment and alternative options in detail. It will be stated clearly that participation in the research 
study is voluntary and that participants can withdraw from the study without losing benefits they 
would otherwise be entitled to. The patient and family members when applicable will be 
encouraged to ask questions, and additional meetings to discuss the treatment options will be 
arranged as necessary. The original signed consent will be maintained according to institutional 
policy.  
Subjects who complete the standard consent and undergo study screening must be documented on 
the Study Screening Log sheet.   
11 PHARMACEUTICAL AND INVESTIGATIONAL DEVICE 
INFORMATION   
11.1 NPC-1C (NEO-102) ARM A ONLY 
11.1.1 Source:  


57 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
NPC-1C is an investigational agent that will be provided by Precision Biologics, Inc., 
manufactured and filled by Cytovance Biologics, Oklahoma City, OK.  The study drug may only 
be requested by the Principal Investigator (or an associate investigator or study pharmacist) from 
the Study Centers’ Pharmacy. The Study Center Pharmacy will document distribution of all study 
drug. 
The Study Center Pharmacy can request drug supplies by e-mailing or phoning the request to 
Precision Biologics: 
 
Anjum Zaki  
 
E-mail: azaki@Precision-Biologics.com 
 
Phone: 301-917-6779  
 
Cc e-mails to kcui@Precision-Biologics.com and smavroukakis@Precision-
Biologics.com. 
After notification, Precision Biologics will complete and forward the shipment request form to 
Almac. Almac personnel will send confirmation of shipment including a FED-EX tracking number 
to designated study site personnel with a cc to the Sponsor when shipment is sent. 
11.1.2 Toxicity:  
The clinical experience with NPC-1C (NEO-102) when given as monotherapy is summarized in 
Section 1.2.4. 
Five (5) patients received NPC-1C (NEO-102) with gemcitabine on this study prior to the 
addition of nab-paclitaxel to the regimen.  The following suspected adverse events were 
observed: 
Adverse event (grade) 
Total # of 
events (N=5) 
Relationship to 
Study Drug 
Anxiety (grade 1) 
1 
Possibly 
Constipation (grade 1) 
1 
Possibly 
Edema (grade 1) 
1 
Possibly 
Fatigue (grade 1) 
1 
Possibly 
Hyperpigmentation of 
hand creases (grade 1) 
1 
Possibly 
Mucositis (grade 1) 
1 
Possibly 
Nausea (grade 1) 
4 
Possibly 
Skin peeling (grade 1) 
1 
Possibly 
Vomiting (grade 1) 
1 
Possibly 
11.1.3 Formulation and preparation:  
The biotherapeutic antibody is purified and formulated in sodium citrate, sodium chloride and 
Tween-80, pH 6.5. The concentration of the NPC-1C (NEO-102) final vialed product is 10 
mg/mL, in 10 mL per vial, thus 100 mg/vial (single use vials).  Each vial is labeled with the drug 


58 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
name and concentration, sponsor name, and storage conditions. The vials are also labeled “for 
investigational use only”. 
11.1.4 Stability and Storage and Infusion:  
Vials of NPC-1C(NEO-102) drug product should be shipped frozen in CREEDO coolers (-20 oC) 
and stored frozen at -20 oC ± 10 oC (short excursions outside this range [but still < 0 oC] can be 
tolerated but must be reported to sponsor) until ready for patient administration.   
The investigator or pharmacist will be required to inventory all shipments with receipts. NPC-1C 
(NEO-102) must be stored in the freezer according to the manufacturer’s instructions and kept in 
a secure area with access restricted to designated study personnel. The investigator or pharmacist 
will keep accurate records of vials and quantities of the study drug used by each study subject. The 
clinical monitor will ensure the use of the medication records is accurate and the investigator or 
pharmacist is accountable. DO NOT ADMINISTER IF THERE IS VISUAL PRECIPITATE IN 
THE BAG OR VIAL. Any unused agent should be discarded as medical waste and should not be 
reused or refrozen for later use. Although there is no current data to demonstrate interaction with 
polyvinyl chloride (PVC) infusion equipment or leaching of plasticizers such as di(2-ethylhexyl) 
phthalate (DEHP) from intravenous equipment, this study will use administration sets with a fluid 
pathway suitable for administering paclitaxel; polyolefin composition (e.g., polypropylene or 
polyethylene) or polyolefin-lined during antibody administration. NPC-1C (NEO-102) infusion 
should be initiated within 2 hours after thawing. The dose level and infusion start and stop times 
must be recorded in the source documents. 
11.1.5 Incompatibilities:  
There are no known incompatibilities with other agents.  
11.1.6 Reconstitution 
Prior to administration to study subjects, vial(s) should be thawed at room temperature, gently 
inverted 10 times, and the required volume for the NPC-1C (NEO-102) dose diluted in 250 mL 
0.9% sodium chloride USP.  NPC-1C (NEO-102) should be administered intravenously. NPC-1C 
(NEO-102) administration should be completed within 8 hours of thaw.  DO NOT ADMINISTER 
IF THERE IS VISUAL PRECIPITATE IN THE BAG OR VIAL.  Any unused agent should be 
discarded as medical waste and should not be reused or re-frozen for later use.  
11.1.7 Administration:  
NPC-1C (NEO-102) will be administered by intravenous continuous infusion using either a 0.20 
or 0.22 low protein binding micron filter with a portable pump. The attachment of the infusion 
pump administration set to the i.v. bag and transport of the study drug to the patient will be 
performed as per standard study site procedures. Infusions of NPC-1C(NEO-102) should be 
administered initially at 0.5 mg/min. Infusion rates may be adjusted as tolerated in 0.5 mg/min 
increments every 30 minutes to a maximum rate of 4 mg/min. Subsequent doses may be 
administered at the highest tolerated rate of infusion, and/or adjusted based on patient tolerance.  
If the patient develops an infusion reaction related to NPC-1C(NEO-102), the infusion rate will 
be adjusted as described in section 3.5.1.3. 


59 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
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INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
11.2 GEMCITABINE 
Gemcitabine is a nucleoside analogue that exhibits antitumor activity which is cell phase-specific 
for the S-phase and for the G1/S-phase boundary of cell division. It is metabolized intracellularly 
by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) 
nucleosides.  Cytotoxic effect of gemcitabine is due to a combination of 2 actions of the dFdCDP 
and dFdCTP nucleosides, which leads to inhibition of DNA synthesis.  Please refer to the FDA-
approved package insert for additional information.   
11.2.1 Source:  
Commercially Available 
11.2.2 Toxicity:  
 Hematologic: Myelosuppression is usually mild to moderate and is more pronounced for 
the granulocyte count. Thrombocytopenia is also commonly reported. 
 Dermatologic: A rash is seen in about 25% of patients and is associated with pruritis in 
about 10% of patients. The rash is usually mild, not dose-limiting, and responds to local 
therapy. Desquamation, vesiculation, and ulceration have been reported rarely. Alopecia is 
reported in <1% of patients. 
 Gastrointestinal: Nausea and vomiting are reported in about two-thirds of patients and 
requires therapy in about 20% of patients. It is rarely (<1%) dose-limiting, and is easily 
manageable with standard antiemetics. Diarrhea is reported in 8% of patients, constipation 
in 6%, and oral toxicity in 7%. Anorexia has also been seen. 
 Renal: Elevation of serum creatinine or BUN; Mild proteinuria and hematuria; Hemolytic 
uremic syndrome. 
 Hepatic: Abnormalities of hepatic transaminase enzymes occur in two-thirds of patients, 
but they are usually mild, nonprogressive, and rarely necessitate stopping treatment. 
However, gemcitabine should be used with caution in patients with impaired hepatic 
function. 
 Pulmonary: Bronchospasm after injection has been reported in less than 1% of patients and 
is usually mild and transient, but parenteral therapy may be required. Dyspnea within a few 
hours of injection is reported in 10% of patients. It is usually mild, short‐ lived, rarely 
dose-limiting, usually abates without any specific therapy. Cough and rhinitis are also 
commonly reported. 
 Neurologic: Somnolence has been reported in 10% of patients, and insomnia is common. 
Dizziness, agitation, paresthesia, confusion, convulsion, and coma have also been reported. 
 Cardiovascular: A few cases of hypotension were reported. Some cases of myocardial 
infarction, congestive heart failure, and arrhythmia have been reported, but there is no clear 
evidence that 


60 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
CONFIDENTIAL:  
NOT TO BE DISCLOSED WITHOUT PERMISSION FROM PRECISION BIOLOGICS FOR QUALIFIED 
INVESTIGATORS AND THEIR IRBS ONLY 
Protocol Edition 13 
Rev.7/19/2016 
 Gemcitabine causes cardiac toxicity. Peripheral edema is reported in about 30% of patients. 
Some causes of facial edema have also been reported. Edema is usually mild to moderate, 
rarely dose limiting, sometimes painful, and reversible after stopping the gemcitabine 
treatment. 
 Other: Flu-type symptoms are reported for about 20% of patients. This includes fever, 
headache, back pain, chills, myalgia, asthenia. Malaise and sweating are also commonly 
reported. Alopecia, fatigue and shortness of breath have also been reported. 
11.2.3 Formulation and preparation:  
Gemcitabine should be reconstituted by adding 0.9 % sodium chloride injection USP (without 
preservatives) to a maximum concentration of 40 mg/mL.  Reconstituted solution should be stored 
at controlled room temperature and used within 24 hours; unused portion should be discarded.  Do 
not refrigerate as crystallization may occur. Shake to dissolve; may further dilute down to 0.1 
mg/mL using 0.9 % sodium chloride injection USP (without preservatives). 
11.2.4 Stability and Storage:  
Gemcitabine is supplied in a sterile form for intravenous use only. Vials of Gemcitabine contain 
either 200 mg or 1 g of gemcitabine HCl (expressed as free base) formulated with mannitol (200 
mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile 
lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH 
adjustment. When prepared as directed, gemcitabine solutions are stable for 24 hours at controlled 
room temperature 20° to 25°C (68° to 77°F). Discard unused portion. Solutions of reconstituted 
gemcitabine should not be refrigerated, as crystallization may occur. 
11.2.5 Administration procedures:  
Gemcitabine is administered intravenously over 30 minutes. 
11.2.6 Incompatibilities:  
May react with strong oxidizing agents (e.g., peroxides, permanganates, nitric acid, etc.). 
 
11.3 PACLITAXEL PROTEIN-BOUND PARTICLES FOR INJECTABLE SUSPENSION (ALBUMIN-
BOUND (NAB-PACLITAXEL, ABRAXANE®) 
11.3.1 Source:  
nab-Paclitaxel will be purchased by the institutions’ pharmacy from commercial sources. 
11.3.2 Toxicity:  
Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity 
of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with 


61 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
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metastatic breast cancer (MBC), 47% of patients with non-small cell lung cancer (NSCLC), and 
38% of patients with pancreatic cancer.  
Nervous System 
Sensory neuropathy is dose- and schedule-dependent. The occurrence of Grade 1 or 2 sensory 
neuropathy does not generally require dose modification.  
Sepsis 
Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in 
combination with gemcitabine. Biliary obstruction or presence of biliary stent were risk factors 
for severe or fatal sepsis.  
Pneumonitis 
Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving 
ABRAXANE in combination with gemcitabine.  
Hypersensitivity 
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have 
been reported.  
Hepatic Impairment 
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, 
administration of ABRAXANE in patients with hepatic impairment should be performed with 
caution. 
Formulation: 
Each mL of the reconstituted formulation will contain 5 mg paclitaxel per milliliter. 
Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing 
volume (mL) = Total dose (mg)/5 (mg/mL). 
The reconstituted suspension should be milky and homogenous without visible particulates. If 
particulates or settling are visible, the vial should be gently inverted again to ensure complete 
resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. 
Discard any unused portion. 
Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile intravenous 
bag [plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type intravenous bag]. 
The use of specialized DEHP-free solution containers or administration sets is not necessary to 
prepare or administer ABRAXANE infusions. The use of an in-line filter is not recommended. 
Parenteral drug products should be inspected visually for particulate matter and discoloration 
prior to administration whenever solution and container permit. 
Stability 


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Unopened vials of ABRAXANE are stable until the date indicated on the package when stored 
between 20ºC to 25ºC (68ºF to 77ºF) in the original package. Neither freezing nor refrigeration 
adversely affects the stability of the product. 
Stability of Reconstituted Suspension in the Vial 
Reconstituted ABRAXANE in the vial should be used immediately, but may be refrigerated at 
2ºC to 8ºC (35.6º–46.4ºF) for a maximum of 8 hours if necessary. If not used immediately, each 
vial of reconstituted suspension should be replaced in the original carton to protect it from bright 
light. Discard any unused portion. 
Stability of Reconstituted Suspension in the Infusion Bag 
The suspension for infusion when prepared as recommended in an infusion bag should be used 
immediately but may be stored at ambient temperature (approximately 25ºC) and lighting 
conditions for up to 4 hours. Discard any unused portion. 
Administration 
ABRAXANE will be administered intravenously over 30 minutes. 
If ABRAXANE administration does not commence within 30 minutes after product preparation, 
the product container should be gently inverted (several repetitions) to re-suspend the drug 
particles before commencing drug administration. 
 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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12 REFERENCES  
1. 
Cancer Facts & Figures2012, Atlanta: American Cancer Society  
2. 
Jemal, A., et al., Cancer statistics, 2010. CA Cancer J Clin, 2010. 60(5): p. 277-300. 
3. 
Sener, S.F., et al., Pancreatic cancer: a report of treatment and survival trends for 
100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll 
Surg, 1999. 189(1): p. 1-7. 
4. 
Geer, R.J. and M.F. Brennan, Prognostic indicators for survival after resection of 
pancreatic adenocarcinoma. Am J Surg, 1993. 165(1): p. 68-72; discussion 72-3. 
5. 
Burris, H.A., 3rd, et al., Improvements in survival and clinical benefit with gemcitabine 
as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin 
Oncol, 1997. 15(6): p. 2403-13. 
6. 
Conroy, T., et al., FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N 
Engl J Med, 2011. 364(19): p. 1817-25. 
7. 
Ko, A.H., FOLFIRINOX: a small step or a great leap forward? J Clin Oncol, 2011. 
29(28): p. 3727-9. 
8. 
Moore, M.J., et al., Erlotinib plus gemcitabine compared with gemcitabine alone in 
patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of 
Canada Clinical Trials Group. J Clin Oncol, 2007. 25(15): p. 1960-6. 
9. 
Kindler, H.L., A double-blind, placebo-controlled, randomized phase III trial of 
gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with 
advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B 
(CALGB). J. Clin. Oncol. 25, 4508–4509 (2007). 
10. 
Laheru, D. and E.M. Jaffee, Immunotherapy for pancreatic cancer - science driving 
clinical progress. Nat Rev Cancer, 2005. 5(6): p. 459-67. 
10a.  
VonHoff DD, T Ervin, FP Arena, et al.  Increased survival in pancreatic cancer with 
nab-Paclitaxel plus Gemcitabine.  N Engl J Med 2013;369:1691-703. 
11. 
Hollinshead, A., et al., Specific active immunotherapy in patients with adenocarcinoma 
of the colon utilizing tumor-associated antigens (TAA). A phase I clinical trial. Cancer, 1985. 
56(3): p. 480-9. 
12. 
Hollinshead, A.C., et al., Separation of skin reactive intestinal cancer antigen from the 
carcinoembryonic antigen of Gold. Science, 1972. 177(4052): p. 887-9. 
13. 
Pullarkat, V., et al., A phase I trial of SD-9427 (progenipoietin) with a multipeptide 
vaccine for resected metastatic melanoma. Clin Cancer Res, 2003. 9(4): p. 1301-12. 
14. 
Hollingsworth, M.A. and B.J. Swanson, Mucins in cancer: protection and control of the 
cell surface. Nat Rev Cancer, 2004. 4(1): p. 45-60. 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
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15. 
Rose, M.C. and J.A. Voynow, Respiratory tract mucin genes and mucin glycoproteins in 
health and disease. Physiol Rev, 2006. 86(1): p. 245-78. 
16. 
Bara, J., et al., Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is 
encoded by the MUC5AC gene. Int J Cancer, 1998. 75(5): p. 767-73. 
17. 
Bara, J., et al., Oncofetal mucin M1 epitope family: characterization and expression 
during colonic carcinogenesis. Int J Cancer, 1991. 47(2): p. 304-10. 
18. 
de Bolos, C., F.X. Real, and A. Lopez-Ferrer, Regulation of mucin and glycoconjugate 
expression: from normal epithelium to gastric tumors. Front Biosci, 2001. 6: p. D1256-63. 
19. 
Kocer, B., J. McKolanis, and A. Soran, Humoral immune response to MUC5AC in 
patients with colorectal polyps and colorectal carcinoma. BMC Gastroenterol, 2006. 6: p. 4. 
20. 
Lau, S.K., L.M. Weiss, and P.G. Chu, Differential expression of MUC1, MUC2, and 
MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol, 
2004. 122(1): p. 61-9. 
21. 
Qi, C.F., et al., Macrophage colony-stimulating factor enhancement of antibody-
dependent cellular cytotoxicity against human colon carcinoma cells. Immunol Lett, 1995. 47(1-
2): p. 15-24. 
22. 
Smith, B.D., et al., K562/GM-CSF immunotherapy reduces tumor burden in chronic 
myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res, 2010. 
16(1): p. 338-47. 
23. 
Gabrilovich, D.I., Combination of chemotherapy and immunotherapy for cancer: a 
paradigm revisited. Lancet Oncol, 2007. 8(1): p. 2-3. 
24. 
Plate, J.M., et al., Effect of gemcitabine on immune cells in subjects with adenocarcinoma 
of the pancreas. Cancer Immunol Immunother, 2005. 54(9): p. 915-25. 
25. 
Hou, J.M., et al., Combination of low-dose gemcitabine and recombinant quail vascular 
endothelial growth factor receptor-2 as a vaccine induces synergistic antitumor activities. 
Oncology, 2005. 69(1): p. 81-7. 
26. 
Soeda, A., et al., Regular dose of gemcitabine induces an increase in CD14+ monocytes 
and CD11c+ dendritic cells in patients with advanced pancreatic cancer. Jpn J Clin Oncol, 
2009. 39(12): p. 797-806. 
27. 
Correale, P., et al., Dendritic cell-mediated cross-presentation of antigens derived from 
colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, 
oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL 
response with antitumor activity in vitro. J Immunol, 2005. 175(2): p. 820-8. 
28. 
Nowak, A.K., et al., Induction of tumor cell apoptosis in vivo increases tumor antigen 
cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J 
Immunol, 2003. 170(10): p. 4905-13. 


65 
A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
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29. 
Nowak, A.K., B.W. Robinson, and R.A. Lake, Synergy between chemotherapy and 
immunotherapy in the treatment of established murine solid tumors. Cancer Res, 2003. 63(15): p. 
4490-6. 
30. 
Dauer, M., et al., Chemosensitization of pancreatic carcinoma cells to enhance T cell-
mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother, 2005. 28(4): 
p. 332-42. 
31. 
Le, H.K., et al., Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c 
mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing 
mice. Int Immunopharmacol, 2009. 9(7-8): p. 900-9. 
32. 
Suzuki, E., et al., Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid 
suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer 
Res, 2005. 11(18): p. 6713-21. 
33. 
Nagaraj, S., et al., Anti-inflammatory triterpenoid blocks immune suppressive function of 
MDSCs and improves immune response in cancer. Clin Cancer Res, 2010. 16(6): p. 1812-23. 
34. 
Philip M. Arlen, L.A.D., Nilofer Saba Azad, Leanne Sophia Sleer, Sherri Haley, Michael 
Morse. A phase I safety study of NPC-1C: A novel, therapeutic antibody to treat pancreas and 
colorectal cancers. in ASCO Annual Meeting 2012. Chicago: J Clin Oncol. 
35. 
Zhang Y, Hochster HS, Stein S, et al. Second-line gemcitabine plus nab-paclitaxel (G+A) 
for advanced pancreatic cancer (APC) after first-line FOLFIRINOX: Single institution 
retrospective review of efficacy and toxicity.  2014 Gastrointestinal Cancers Symposium.  J Clin 
Oncol 32, 2014 (supple 3, abstr 344). 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
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13 APPENDICES 
13.1 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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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
Gemcitabine and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer 
Previously Treated with FOLFIRINOX  
 
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13.2 APPENDIX B: ELIGIBILITY CHECKLIST 
 
  


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus 
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13.3 APPENDIX C: NPC-1C IMMUNOHISTOCHEMICAL STAINING REQUEST  
 
 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and nab-Paclitaxel alone in 
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13.4 APPENDIX D: HYPERSENSITIVITY/INFUSION REACTION ALGORITHM 
 
 
 
 
 
 
 
 
 
 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and nab-Paclitaxel alone in 
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13.5 APPENDIX E: SUMMARY OF CORRELATIVE STUDIES 
Tissue 
Sample 
Type 
Test 
Lab 
performing 
testing 
Tubes  
ALL SITES: 
(except NCI) 
Tubes NCI Site 
ONLY:  
Timing of Blood 
Draws 
Storage and Shipping  
Blood 
Immune Response to 
Mesothelin by 
ELISPOT 
NCI (Dr. Kopp 
Lab) 
CPT/ Heparin 
tubes (green 
tops) 
16 mL (2-8mL 
tubes) 
EDTA (purple 
tops) 20mL (2-
10mL tubes) 
C1D1 
C2D1 
(optional) C3D1, 
Off Tx ** 
Process as per SOP #5 
Ship as per SOP #6 
CD4, CD8 and 
regulatory T-Cells 
(CD4+ CD25high) 
NCI (Dr. 
Greten Lab) 
CPT/ Heparin 
tubes (green 
tops) 
16 mL (2-8mL 
tubes) 
EDTA (purple 
tops) 20mL (2-
10mL tubes) 
C1D1 
C2D1 
(optional) C3D1, 
Off Tx ** 
Process as per SOP #5 
Ship as per SOP #6 
Myeloid-derived 
suppressor cells 
(MDSC) Quantification  
 
NCI (Dr. 
Greten Lab) 
CPT/ Heparin 
tubes (green 
tops)  
16 mL (2-8mL 
tubes) 
EDTA (purple 
tops) 20mL (2-
10mL tubes) 
C1D1 
C2D1 
(optional) C3D1, 
Off Tx ** 
Process as per SOP #5 
Ship as per SOP #6 
Cytokines 
 
NCI (Dr. 
Greten Lab) 
SST (red top 
tubes) 
 10 mL (2- 5mL 
tubes) 
SST (red top 
tubes) 10 mL (2- 
5mL tubes) 
C1D1 
C2D1 
(optional) C3D1, 
Off Tx ** 
Process as per SOP #4; 
Ship as per SOP #6 
Blood  
HACA (Arm A Only) 
Precision 
Biologics, Inc. 
SST (red top 
tube)-5 mL (1- 
5mL tube) 
SST (red top 
tube)-5 mL (1- 
5mL tube) 
C1D1 
Off Tx 
Process as per SOP #2; 
Store and Ship Frozen  
(-70oC) as per SOP #3 
** It is also optional to perform these analyses at C3D1 and at the end of treatment in patients participating at the NIH, at the PI 
discretion. 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and 
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13.6 APPENDIX F: EXCERPTED FROM ABRAXANE FOR INJECTABLE SUSPENSION (PACKAGE INSERT) 
(http://www.abraxane.com/downloads/Abraxane_PrescribingInformation.pdf 
 
 
 


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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine and 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine 
and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer Previously Treated with 
FOLFIRINOX  
 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine 
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FOLFIRINOX  
 
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FOLFIRINOX  
 
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FOLFIRINOX  
 
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A Multicenter randomized phase II Study of NPC-1C in Combination with Gemcitabine and nab-Paclitaxel versus Gemcitabine 
and nab-Paclitaxel alone in Patients with Metastatic or Locally Advanced Pancreatic Cancer Previously Treated with 
FOLFIRINOX  
 
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13.7 APPENDIX G INVESTIGATOR AGREEMENT AND SIGNATURE PAGE 
 
 
Protocol Title:  
A Multicenter Randomized Phase II Study of NPC-1C in Combination with 
Gemcitabine and nab-Paclitaxel versus Gemcitabine and nab-Paclitaxel alone in 
Patients with Metastatic or Locally Advanced Pancreatic Cancer Previously 
Treated with FOLFIRINOX 
 
Study drug:   
NPC-1C (NEO-102) 
 
Protocol Number:  Precision Biologics-1201 (PB-1201) 
 
Edition Number:  
13 
 
I have read the Protocol, and I agree to conduct the study as detailed herein and in compliance with ICH 
Guidelines for Good Clinical Practice and applicable regulatory requirements and to inform all who assist 
me in the conduct of this study of their responsibilities and obligations. 
 
 
 
Principal Investigator (printed name) 
 
 
 
 
 
Principal Investigator (signature) 
 
Date 
 
 
 
 
 
 
 
Investigational site or name of institution and location (printed)