A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With AMG 479 in Subjects With Advanced, Refractory Solid Tumors
Phase: PHASE1
Conditions: Colorectal Cancer, Locally Advanced, Metastatic Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Sarcoma, Solid Tumors
Sponsor: NantCell, Inc.

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 1 of 125 
 
A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With 
AMG 479 in Subjects With Advanced, Refractory Solid Tumors  
AMG 479 and AMG 655 
Amgen Protocol Number 20070411 
 
EudraCT number: 2008-005074-12 
Clinical Study Sponsor: 
Amgen, Inc. 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Phone: +1 (805).447-1000 
Key Sponsor Contact: 
Francesco Galimi, MD PhD 
Clinical Research Medical Director  
Amgen Inc 
Phone:  +1 (805) 447-0664 
Fax:  +1 (805) 480-1291 
E-mail: francesco.galimi@amgen.com 
 
Lynn Manlapaz-Espiritu 
Clinical Research Study Manager 
Amgen Inc 
Phone: +1 (805) 313-8071  
Fax: +1 (650) 837-9716 
E-mail: lenilyne@amgen.com  
Licensee 
Amgen Inc. 
Date: 
06 October 2008 
Amendment 1: 
19 November 2008 
Superseding Amendment 1 
12 January 2010 
Amendment 2 
25 May 2011 
Confidentiality Notice 
This document contains confidential information of Amgen Inc.  
This document must not be disclosed to anyone other than the study staff and members 
of the independent ethics committee/institutional review board.   
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc.  
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number:  US: 1- 800-77-AMGEN; Canada: 1-866-50-
AMGEN; all other countries: 1-805-447-5000.  For all other study-related questions, 
continue to contact the Key Sponsor Contact. 

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 2 of 125 
 
Investigator’s Agreement 
I have read the attached protocol entitled A Phase 1b/2 Open Label, Dose Escalation 
Study of AMG 655 in Combination With AMG 479 in Subjects With Advanced, Refractory 
Solid Tumors, dated 25 May 2011, and agree to abide by all provisions set forth therein. 
I agree to comply with the International Conference on Harmonisation Tripartite 
Guideline on Good Clinical Practice and local ethics and/or institutional review board 
regulations and guidelines. 
I agree to ensure that Financial Disclosure Statements will be completed by: 
• 
me (including, if applicable, my spouse [or legal partner] and dependent children) 
• 
my subinvestigators (including, if applicable, their spouses [or legal partners] and 
dependent children) 
at the start of the study and for up to 1 year after the study is completed, if there are 
changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen Inc.  
 
 
 
Signature 
 
 
Name of Principal Investigator 
 
Date (DD Month YYYY) 

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 3 of 125 
 
Protocol Synopsis 
Title:  A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With 
AMG 479 in Subjects With Advanced, Refractory Solid Tumors  
Study Phase: 1b/2  
Indications   
Part 1:  Advanced, treatment-refractory solid tumors 
Part 2:  Advanced non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic 
cancer, ovarian cancer, or sarcoma 
Primary Objectives (Section 1.1)  
Part 1:  To identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerated as 
determined by the incidence of dose limiting toxicity (DLT).  
Part 2:  To estimate the efficacy, as measured by the objective response rate (ORR; confirmed 
complete response [CR] and partial response [PR] using modified Response Evaluation Criteria 
in Solid Tumors [RECIST]) of AMG 655 in combination with AMG 479. 
Secondary Objectives (Section 1.2)  
Part 1 
• 
To evaluate the safety and tolerability of AMG 655 in combination with AMG 479  
• 
To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation  
• 
To evaluate the pharmacokinetics (PK) of AMG 655 and of AMG 479 
Part 2   
• 
To estimate the efficacy of AMG 655 in combination with AMG 479, as measured by time to 
response, duration of response, and progression-free survival (PFS)  
• 
To evaluate the safety and tolerability of AMG 655 in combination with AMG 479  
• 
To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation  
• 
To evaluate the PK of AMG 655 and of AMG 479 
Exploratory Objectives (Section 1.3) 
Parts 1 and 2   
• 
To investigate the relationship between AMG 655 PK and AMG 479 PK and treatment 
outcomes (including clinical and pharmacodynamic endpoints)  
• 
To investigate the baseline biomarker profile and pharmacodynamic response, as assessed 
by AMG 655 and AMG 479 biomarkers, and correlation with treatment outcomes  
• 
Tumor tissue analysis of somatic gene mutations that function to regulate the IGF-1/IGF-1R 
and/or apoptosis pathways and other genes that are known to be involved in the 
development and progression of solid tumors (Required for subjects with CRC, ovarian 
cancer, and sarcoma; optional, if tissue is available, for subjects with NSCLC and pancreatic 
cancer).  
• 
To investigate the genetic variations in cancer genes, drug target and pathway genes, and 
other biomarker genes, and correlation with treatment outcomes (optional for subjects; 
separate informed consent required). 
Part 2 
• 
To estimate the efficacy of AMG 655 in combination with AMG 479 using clinical benefit rate 
(CR, PR, and disease stabilization [SD] ≥ 12 weeks, as measured by modified RECIST)    

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 4 of 125 
 
Study Hypotheses 
Part 1:  AMG 655 in combination with AMG 479 is safe and tolerated as determined by the 
incidence of DLT when administered to subjects with advanced, treatment-refractory solid tumors.   
Part 2:  The combination of AMG 655 with AMG 479 will have an acceptable safety profile and 
will be associated with at least 3 objective responses out of 15 evaluable subjects in at least 1 
cohort (advanced NSCLC [squamous and/or non-squamous histology], CRC, pancreatic cancer, 
ovarian cancer, and/or sarcoma). 
Study Design (Section 3.1) 
This is a multi-center, open-label, 2-part phase 1b/2 study of AMG 655 in combination with 
AMG 479. 
Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 
that is safe and tolerable as determined by the incidence of DLT.  The maximum dose of 
AMG 655 planned is 15 mg/kg Q3W. There will be no intra-subject dose escalations in each of 
the planned dose cohorts. 
Part 2 will open once a dose of AMG 655 has been identified that is safe and tolerated based on 
the incidence of DLT in Part 1 and evaluate the safety and estimate the efficacy (as measured by 
ORR) of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment 
of patients with advanced NSCLC (Cohort 1: non-squamous histology; Cohort 2: squamous 
histology), CRC (Cohort 3), pancreatic cancer (Cohort 4), ovarian cancer (Cohort 5), and 
sarcoma (Cohort 6).  Enrollment into the 6 cohorts will occur in parallel, independent of one 
another.   
Parts 1 and 2  
AMG 655 and AMG 479 treatment will be administered Q3W until disease progression, 
intolerable adverse event, death, withdrawal of consent, or administrative decision, for up to 
24 months from the date of first study treatment (study day 1).  Subjects who have completed 
24 months of AMG 655 and/or AMG 479 treatment and who continue to benefit from treatment 
may be eligible for continued treatment with AMG 655 and/or AMG 479 by extension protocol or 
as provided for by the local country’s regulatory mechanism (Section 13).  Study treatment will 
cease if a subject experiences progressive disease (PD), death, intolerable adverse event(s), 
withdraws consent or due to an administrative decision (by the investigator or Amgen).   
Radiological imaging (per modified RECIST) will be performed every 6 weeks (± 7 days) during 
the first 6 months of the study, and every 9 weeks (± 7 days) thereafter, until subjects develop PD 
(per modified RECIST) or begin a new cancer treatment.  Safety follow-up visits will occur 30 
(+ 7) days and 60 (+ 14) days after the last dose of protocol-specified treatment.  Subjects will be 
contacted every 3 months (± 2 weeks) in the long-term follow-up, for up to 36 months from the 
date of the last subject enrolled, to assess survival.  
To mitigate potential safety risks, the first 3 subjects in Part 1 will be enrolled at a rate of 
≤ 1 subject per week.  The study team will review Part 1 dose level cohort data to make 
recommendations on dose escalation, dose selection and dose stopping.  During Part 2 of the 
study, the study team will review safety data after a total of at least 15 subjects (Interim Analysis 
[IA] 1) and 45 subjects (IA 2) have been enrolled and have completed 1 cycle of treatment, and 
additionally as warranted during the conduct of this clinical trial. 
The Study Schema is provided at the end of the Protocol Synopsis section.  
Primary and Secondary Endpoints (Section 10.2) 
Part 1:  The incidence of adverse events and clinical laboratory abnormalities defined as DLT  
Part 2:  ORR (confirmed CR and PR, by modified RECIST) 

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 5 of 125 
 
Secondary Endpoints   
Part 1 
• 
The incidence of adverse events and laboratory abnormalities not defined as DLT  
• 
The incidence of anti-AMG 655 antibody formation and anti-AMG 479 antibody formation  
• 
PK (Cmax and Cmin for AMG 655 and AMG 479)  
Part 2 
• 
Time to response  
• 
Duration of response  
• 
PFS 
• 
The incidence of adverse events and laboratory abnormalities  
• 
The incidence of anti-AMG 655 antibody formation and anti-AMG 479 antibody formation  
• 
PK (Cmax and Cmin for AMG 655 and AMG 479)  
Sample Size:  Approximately 99 to 108 (Part 1:  approximately 9 to 18 DLT-evaluable subjects; 
Part 2: approximately 90 response-evaluable subjects) (See Section 3.3 and Section 10.3) 
Summary of Subject Eligibility Criteria:  (See Section 4.1 and Section 4.2 for a complete list of 
eligibility criteria.) 
Key Inclusion Criteria  
• 
Locally advanced or metastatic, treatment-refractory solid tumors (Part 1) 
• 
Locally advanced or metastatic NSCLC (up to 2 prior treatment regimens), CRC (up to 2 prior 
treatment regimens), pancreatic cancer (up to 1 prior treatment regimen), ovarian cancer (up 
to 2 prior treatment regimens), or sarcoma (up to 2 prior treatment regimens) (Part 2) 
• 
Measurable disease (at least one measurable lesion) (Part 2) 
• 
≥ 16 years old  
• 
Life expectancy ≥ 3 months 
• 
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1  
• 
Adequate organ function (liver, kidneys, bone marrow, coagulation, heart, glycemic function) 
Key Exclusion Criteria  
• 
Presence of uncontrolled central nervous system (CNS) metastasis  
• 
Prior treatment with death receptor agonists (eg, rhApo2L/TRAIL [AMG 951], apomab, 
mapatumumab, lexatumumab, CS-1008) 
• 
Prior treatment with IGF receptor antagonists (eg, CP-751,871, MK0646, AVE1642 or 
IMC-A12) 
• 
Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or approved 
anticancer proteins/antibodies therapy ≤ 28 days before enrollment, except: 
− 
In Part 1, patients may continue approved hormonal therapy as medically indicated 
• 
Any prior or synchronous malignancy (except for non-melanoma skin cancer or in situ 
cervical cancer) other than the study disease, unless treated with curative intent with no 
evidence of disease ≥ 3 years before enrollment (Part 2) 
• 
Any clinically significant medical condition other than cancer, including cardiovascular 
disease or chronic obstructive pulmonary disease, which in the opinion of the investigator 
could interfere with the safe delivery of study treatment or increase risk of toxicity 

Approved 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 6 of 125 
 
Investigational Product Dosage and Administration:  See Section 6, Treatment Procedures; 
Section 11, Investigational Products; Appendix C for AMG 655 and AMG 479 Pharmacy Guides. 
Part 1 
Cohort 1:  AMG 479 18 mg/kg plus AMG 655 1 mg/kg IV on day 1 of each Q3W cycle  
Cohort 2:  AMG 479 18 mg/kg plus AMG 655 3 mg/kg IV on day 1 of each Q3W cycle 
Cohort 3:  AMG 479 18 mg/kg plus AMG 655 15 mg/kg IV on day 1 of each Q3W cycle 
There will be no intra-subject dose escalations in each of the planned dose cohorts.  Alternative 
AMG 655 doses (eg, 0.3 mg/kg IV) and/or AMG 479 doses may be explored based on safety and 
PK data. 
Part 2:  AMG 479 18 mg/kg plus AMG 655 at the dose selected in Part 1 (up to 15 mg/kg) IV on 
day 1 of each Q3W cycle 
AMG 655 and AMG 479 will be administered through a peripheral line or indwelling 
catheter using a nonpyrogenic, low protein binding filter with a 0.2- or 0.22-micron pore 
size in-line filter infusion set-up.   
Control Group:  There is no control group. 
Key Study Procedures:  See Section 7.1 and Schedule of Assessments (Appendix A) for 
details.  
Screening Procedures  
• 
Review of inclusion and exclusion criteria  
• 
Medication and medical history, concomitant medications/treatment(s), adverse events  
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including height and weight  
• 
ECOG performance status assessment  
• 
Laboratory tests; including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
Submission of formalin-fixed, paraffin-embedded tumor tissue (paraffin tumor block, or slides) 
and associated pathology reports (Required for subjects with CRC, ovarian cancer, and 
sarcoma; optional, if tumor tissue is available, for subjects with NSCLC and pancreatic 
cancer). 
• 
12-lead electrocardiogram (ECG)  
• 
Radiological imaging to assess disease extent (CT scan or MRI of the brain, chest, abdomen, 
and all other sites of disease; within 28 days prior to enrollment)  
Treatment and Follow-up Procedures 
• 
Recording of adverse events and concomitant medications  
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including weight, and ECOG performance status assessment  
• 
Laboratory tests; including hematology, chemistry, pregnancy test  
• 
Samples for biomarkers and anti-AMG 655 and anti-AMG 479 antibodies  
• 
Samples for AMG 655 and AMG 479 PK 
• 
ECG  
• 
Radiological imaging to assess disease extent (CT scan or MRI [same modality throughout 
the study] of the chest, abdomen, and all other sites of disease [except: brain imaging only as 
clinically indicated] every 6 weeks [± 7 days] during the first 6 months of the study, and every 
9 weeks [± 7 days] thereafter)  

Approved
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 7 of 125 
Statistical Considerations:  See Section 10 for details.   
Analyses will be presented separately for Part 1 and Part 2 of the study. 
Part 1:  A sample size of approximately 3 to 6 DLT-evaluable subjects per cohort was selected to 
identify a dosing regimen of AMG 655 in combination with AMG 479 that is safe and tolerated 
based on the incidence of DLT.  A listing and summary of the incidence of DLT will be presented 
for each cohort.  All other safety data collected in Part 1 of the study will be summarized using 
appropriate descriptive statistics.  The study team will review Part 1 dose level cohort data after at 
least 3 subjects have completed the DLT window to make recommendations on dose escalation, 
dose selection and dose stopping.  
Part 2 
Approximately 90 subjects (15 response-evaluable subjects per cohort [tumor type]) will be 
enrolled in Part 2.  This part of the study will identify tumor types, in which further study of 
AMG 655 in combination with AMG 479 is warranted, using the following criterion: at least 3 out 
of 15 subjects have an objective response (an ORR of at least 20%).  If 2 or less responders are 
observed in a given cohort, then all other parameters of clinical benefit (including clinical benefit 
rate and PFS, within others) and of patient safety will be evaluated to determine if further study is 
warranted of the AMG 655 and AMG 479 combination in that tumor type.  The primary endpoint is 
ORR.  The proportion of subjects with an objective response (confirmed CR or PR by modified 
RECIST) per local investigator assessment with corresponding 95% exact confidence intervals 
will be presented for each Part 2 cohort.  All safety data collected in part 2 of the study will be 
summarized per cohort and in aggregate over all cohorts using appropriate descriptive statistics.  
During Part 2 of the study, the study team will review safety data after a total of at least 15 
subjects (Interim Safety Analysis [IA] 1) and 45 subjects (IA 2) have been enrolled and have 
completed 1 cycle of treatment, and additionally as warranted during the conduct of this clinical 
trial.  Unless safety concerns arise, enrollment will not be stopped during the Part 2 safety 
reviews.   
The primary analysis of Part 2 will provide the proportion of subjects with an objective response 
and is planned to occur after all subjects have had the opportunity to complete 4 cycles of 
treatment.  If the recruitment rate is not consistent across cohorts, a piecewise approach to the 
primary analysis may be taken with the analysis for the quickest recruiting cohorts occurring first. 
The final analysis of this study will occur after all subjects have progressed, died, or terminated 
the study for other reasons. 
Sponsor/Licensee:  Amgen, Inc. 

 
Approved 
 
 
 
Product:  AMG 655 and AMG 479 
Protocol Number:  20070411 
Date:  25 May 2011 
Page 8 of 125 
 
Study Design and Treatment Schema 
 Dose Cohort  
 Review
 
 Determine 
 AMG 655 MTD
PART 1
DOSE ESCALATION SEGMENT
PART 2
DOSE EVALUATION SEGMENT
PART 2  ENROLLMENT 
AMG 655 15 mg/kg or MTD
Cohort 1  (n=15) 
NSCLC (non-squamous histology)
AMG 655 1 mg/kg
AMG 479 18 mg/kg
SAFETY REVIEW TEAM REVIEWS DOSE COHORTS, RECOMMENDS PART 2 REGIMEN
AMG 479 PLUS AMG 655 AT DOSE IDENTIFIED IN PART 1 
STUDY TREATMENT 
 Investigational Products (IP): AMG 479 and AMG 655 Administered on Day 1 of Each 21 Day Cycle (Q3W) (for up to 24 Months From Study Day 1). There 
will be no intra-subject dose escalations in each of the planned dose cohorts of the phase 1b portion (part 1) of the study.
Cohort 1 (n=3 to 6)
AMG 479 18 mg/kg
 Dose Cohort  
 Review
 
 Determine 
 AMG 655 MTD
AMG 655 3 mg/kg
AMG 479 18 mg/kg
Cohort 2 (n=3 to 6)
AMG 655 15 mg/kg
AMG 479 18 mg/kg
Cohort 3 (n=3 to 6)
 Dose Cohort  
 Review
 Determine 
 AMG 655 MTD 
 or Target Dose
 STOP *
Cohort 3  (n=15) 
Colorectal Cancer
Cohort 4  (n=15) 
Pancreatic cancer
Cohort 2  (n=15) 
NSCLC (squamous histology)
Cohort 6  (n=15) 
Sarcoma
AMG 655 15 mg/kg or MTD
AMG 479 18 mg/kg
AMG 655 15 mg/kg or MTD
AMG 479 18 mg/kg
AMG 655 15 mg/kg or MTD
AMG 479 18 mg/kg
AMG 655 15 mg/kg or MTD
AMG 479 18 mg/kg
Cohort 5  (n=15) 
Ovarian cancer
AMG 655 15 mg/kg or MTD
AMG 479 18 mg/kg
PART 1 ENROLLMENT 
* Alternative doses of AMG 655            
  and/or AMG 479 may be explored 
  at the discretion of the study team