Clinical trial NCT00807612
Conditions: Advanced Squamous Non-Small Cell Lung Cancer
Keywords: AMG 479 IGF-1R Apoptosis Monoclonal Antibody Advanced Squamous Non-Small Cell Lung Cancer antibody 1st-line
Sponsor: NantCell, Inc.
Start date: 2009-01-01; Completion date: 2010-08-01
Enrollment: 15 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a global, multicenter, 2-part, open-label phase 1b and single-arm phase 2 study designed to evaluate the safety and efficacy of AMG 479 in combination with paclitaxel and carboplatin for the first-line treatment of advanced squamous non-small cell lung carcinoma.

Detailed description:

Arms: arm 1: AMG 479 at 18 mg/kg in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for 24 months from study day 1 arm 2: AMG 479 at 12 mg/kg in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg monotherapy for 24 months from study day 1 arm 3: AMG 479 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for 24 months from study day 1

(AMG 479 dose in Part 2 will be the final AMG 479 dose from Part 1)
Interventions: intervention 1: AMG 479 intervention 2: AMG 479 intervention 3: Carboplatin intervention 4: AMG 479 intervention 5: Paclitaxel
Intervention descriptions: intervention 1: AMG 479 at 12 mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 12 mg/kg IV monotherapy for up to 24 months from study day 1 intervention 2: AMG 479 at 18mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on Day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 18 mg/kg IV monotherapy for up to 24 months from day 1 intervention 3: Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6 intervention 4: AMG 479 IV in combination with chemotherapy on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 24 months from study day 1. The AMG 479 dose to be used will be the final AMG 479 dose explored from Part 1 intervention 5: Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6

Protocol documents:
Prot_SAP_000.pdf: 
Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 1 of 114 
 
Title: A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and 
Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell 
Lung Cancer  
AMG 479 
Amgen Protocol Number 20080257 
 
Clinical Study Sponsor: 
Amgen Inc 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
Phone: 805-447-1000 
Key Sponsor Contact: 
Jesse McGreivy, MD 
Clinical Research Medical Director 
Amgen, Inc. 
1120 Veterans Blvd. 
ASF B3-3 
South San Francisco, CA 94080 
Phone: 650-244-2634 
Fax: 650-837-9716 
Email: jessem@amgen.com 
 
Nancy Kenyon 
Clinical Research Study Manager-U.S. 
Amgen, Inc. 
Mail Stop 38-2-B 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Phone: 805-447-5737 
Fax: 805-480-1291 
Email: nkenyon@amgen.com 
 
Polly Rawlings 
Clinical Research Study Manager-Outside U.S. 
Amgen, Inc. 
1 Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH  
UK 
Tel: +44 (0)1895 525476 
Fax: +44 (0)1895 525107 
Email: prawling@amgen.com 
Date: 
02-September-2008 
 
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 sites: 1- 800-77-AMGEN 
For all other countries: 1-805-447-5000 
For all other study-related questions, continue to contact the Key Sponsor Contact. 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 2 of 114 
 
Investigator’s Agreement 
I have read the attached protocol entitled “A Phase 1b/ 2 Study of AMG 479 in 
Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced 
Squamous Non-Small Cell Lung Cancer” dated 02-September-2008, 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 Ethic Committee 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) 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 3 of 114 
 
Protocol Synopsis 
Title:  A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and Carboplatin for the 
First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer 
Study Phase:  1b/ 2 
Indication:  First-line advanced squamous Non-Small Cell Lung Cancer (NSCLC) 
Primary Objective:   
Part 1 (Phase 1b): To identify a dose of AMG 479 in combination with paclitaxel/carboplatin that 
can be administered safely and is tolerated as determined by the incidence of dose-limiting 
toxicity (DLT). 
Part 2 (Phase 2): To estimate the efficacy of AMG 479 (at the final dose selected in Part 1) in 
combination with paclitaxel/carboplatin as measured by the objective response rate (ORR) as per 
modified RECIST by investigator review. 
Secondary Objective(s):   
Part 1: 
To evaluate the safety and tolerability of de-escalating doses of AMG 479 in combination with 
paclitaxel/carboplatin in terms of the incidence of adverse events and laboratory abnormalities not 
defined as dose-limiting toxicities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Subjects who received the final dose in Part 1 will be included in the Part 2 efficacy and safety 
analysis. 
Part 2: 
To estimate the efficacy of AMG 479 in combination with paclitaxel/carboplatin as measured by 
progression free survival (PFS), time to progression (TTP), duration of response (DOR), 1 and 2 
year survival rates, and overall survival (including subjects who received the final dose in Part 1). 
To evaluate the safety and tolerability of AMG 479 in combination with paclitaxel/carboplatin in 
terms of the incidence of adverse events and laboratory abnormalities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Exploratory Objective(s):   
Parts 1 and 2: 
To evaluate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (optional; collect-and-hold approach). 
To correlate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST 
with pharmacodynamic measures (serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway). 
To investigate the genetic variation in drug metabolism genes, cancer genes, and drug target 
genes and correlate with outcomes related to AMG 479 in combination with paclitaxel/carboplatin 
therapy (requires a separate informed consent, optional for subjects). 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 4 of 114 
 
To investigate tumor tissue analysis of somatic gene mutations that function to regulate the IGF-
1R pathway and other genes that are known to be involved in the development and progression 
of solid tumors (if tissue is available). 
To investigate mRNA and protein expression of genes that are known to regulate the IGF-1/IGF-
1R pathway in archival tumor specimens. This will include but will not be limited to analysis of 
PTEN expression by immunohistochemistry (if tissue is available). 
Hypotheses:   
In Part 1, AMG 479 can be given with paclitaxel/carboplatin at a safe and tolerated dose as 
determined by the incidence of DLTs. 
In Part 2, the ORR of AMG 479 in combination with paclitaxel/carboplatin will exceed that for the 
historical control of paclitaxel/carboplatin alone (See 10.3.2 for the weighted historical average). 
Study Design:  
Part 1 is an open-label, single arm dose de-escalation phase 1b segment to determine the safety 
and tolerability of AMG 479 in combination with paclitaxel/carboplatin every 3 weeks (Q3W) for 4 
to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 as first-line 
therapy in advanced squamous NSCLC. 
Part 2 is a single arm open-label phase 2 segment in which AMG 479 in combination with 
paclitaxel/carboplatin Q3W for 4 to 6 cycles followed by AMG 479 monotherapy for up to 24 
months from study day 1 will be used to determine the efficacy and safety of this regimen.  The 
dose of AMG 479 used in Part 2 will be based on the final dose of AMG 479 from Part 1. 
In Part 1, approximately 6 to 9 subjects will be enrolled in Cohort 1 to receive AMG 479 at 18 
mg/kg in combination with paclitaxel (200 mg/m2) and carboplatin (AUC 6) IV on day 1 every 3 
week cycle for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for up to 24 months 
from study day 1.  Pending review of dose limiting toxicities from Cohort 1 by the study team, in 
consultation with participating investigator(s), a lower dose of AMG 479 at 12 mg/kg in 
combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg 
monotherapy for up to 24 months from study day 1 may be administered to an additional 6 to 9 
subjects in Cohort 2 (please see Section 3.1 Study Design for further clarification here). 
In Part 2, an additional 31 to 34 subjects will be treated with AMG 479 at the final dose from Part 
1 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at the final 
dose from Part 1 monotherapy for up to 24 months from study day 1.  Part 2 will be open 
following the review of the Part 1 data by the study team, in consultation with participating 
investigator(s) as outlined in Section 3.1. 
In Part 1 and Part 2, AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter). 
In Part 1 and Part 2, all subjects receive AMG 479 in combination with paclitaxel/carboplatin for 4 
to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 to be 
administered until progression of disease, intolerable adverse event, death, or withdrawal of 
consent. 
Radiological imaging to assess progressive disease (PD) 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. 
A follow-up visit 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 to assess disease and survival status for up to 36 months from the date of the last 
subject enrolled in the study.  Please refer to the Study Schema for an overview of the 2-part 
study design. 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 5 of 114 
 
Primary and Secondary Endpoints: 
Primary Endpoints: 
Part 1:  
• 
The incidence of adverse events and clinical laboratory abnormalities defined as dose-
limiting toxicities 
Part 2:  
• 
ORR as per modified RECIST criteria by investigator review 
 
Secondary Endpoints 
Part 1: 
• 
The incidence of adverse events and laboratory abnormalities not defined as dose 
limiting toxicities 
• 
The incidence of anti-AMG 479 antibody formation 
Part 2: 
• 
PFS, TTP, DOR, 1 and 2 year survival rates, and OS including subjects who received the 
final dose in Part 1 
• 
The incidence of adverse events and laboratory abnormalities 
• 
The incidence of anti-AMG 479 antibody formation 
 
Part 1 and 2 (PK): 
• 
Cmax and Cmin for AMG 479 for all subjects 
• 
Cmax, C24 or AUC24 for paclitaxel and carboplatin in subjects with intensive sampling  
 
Exploratory Endpoints 
Part 1 and Part 2: 
• 
ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (this analysis is optional and may be initiated by the 
sponsor; all radiographic images from the study will be sent to a central imaging vendor 
with a collect-and-hold approach) 
• 
Pharmacodynamic response: serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway 
• 
Analysis of genetic variation (optional separate informed consent required)  
• 
Tumor tissue analysis of somatic gene mutations that function to regulate the IGF-1R 
pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available) 
• 
Analysis of mRNA and protein expression of genes that are known to regulate the IGF-
1/IGF-1R pathway in archival tumor specimens (if tissue is available). This will include but 
will not be limited to analysis of PTEN expression by immunohistochemistry. 
 
Sample Size:  Part 1: 6 to 18 subjects; Part 2: 31 to 34 subjects (see Section 10.3 Sample Size 
for rational) 
Summary of Subject Eligibility Criteria: See Section 4 for further details 
Key Inclusion Criteria 
• 
Histologically or cytologically confirmed advanced squamous NSCLC defined as stage 
IIIB with malignant effusion or stage IV or recurrent disease (recurrent disease is defined 
as documented disease progression following complete surgical resection for stage I or II 
disease).  Subjects with mixed tumors with squamous features are eligible unless small 
cell elements are present in which case the subject will be ineligible.  Cytologic or 
histologic elements can be established on metastatic tumor aspirates or biopsy. 
Confirmation must be prior to enrollment.   
• 
Measurable disease as defined per modified RECIST criteria (see Appendix F) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status of  0 or 1 (see 
Appendix E) 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 6 of 114 
 
• 
≥18 years old 
• 
Adequate glycemic function, for subjects with known diabetes (Type 1 or 2), as follows: 
• 
Must be controlled with a glycosylated hemoglobin (HgbA1c) of ≤ 8.0% 
• 
Documented fasting blood sugars ≤ 160 mg/dL 
Key Exclusion Criteria 
• 
Untreated or symptomatic central nervous system (CNS) metastases 
 
Subjects with a history of CNS metastases that are both definitively treated and 
stably controlled are eligible if all of the following apply: 1) definitive therapy has 
been administered (surgery and/or radiation therapy); 2) there is no additional 
treatment planned for brain metastases; 3) the subject is clinically stable; 4) the 
subject is off corticosteroids or on a stable dose of corticosteroids for at least 14 
days prior to enrollment. 
• 
Prior anti-cancer therapy as follows: 
 
Any prior chemotherapy for advanced squamous NSCLC 
 
Any prior adjuvant or neo-adjuvant chemotherapy for squamous NSCLC 
 
Any prior chemoradiation for squamous NSCLC 
 
Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for 
peripheral lesions ≤ 14 days prior to enrollment for squamous NSCLC 
• 
Currently or previously treated with biological, immunological or other therapies for 
squamous NSCLC 
 
Investigational Product Dosage (AMG 479) and Chemotherapy Administration: 
Part 1 (dose de-escalation design): 
• 
Cohort 1: AMG 479 18 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 18 
mg/kg IV monotherapy for up to 24 months from study day 1 
• 
Cohort 2: AMG 479 12 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 12 
mg/kg IV monotherapy for up to 24 months from study day 1 
Part 2:  
• 
AMG 479 IV in combination with paclitaxel 200 mg/m2 and carboplatin (AUC 6) IV on day 1 of 
every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 24 
months from study day 1.  The AMG 479 dose to be used in Part 2 will be the final AMG 479 
dose explored from Part 1. 
For Part 1 and Part 2: AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter).  Moreover, for Part 1 and Part 2, AMG 479 will be given in combination 
with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for up to 24 
months from study day 1 until progression of disease, intolerable adverse event, death, or 
withdrawal of consent. 
Procedures:  See Section 7.1 and Schedule of Assessments (Appendix A) for details. 
Key Screening Procedures (see Section 7.2 for a complete list): 
• 
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, weight, and ECOG performance status assessment  


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 7 of 114 
 
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
If available, submission of paraffin-embedded tumor tissue (paraffin tumor block, or slides) 
and all available pathology reports 
• 
12-lead electrocardiogram (ECG)  
• 
Radiological imaging to assess disease extent (CT scan or MRI of the brain, chest, abdomen, 
pelvis, and all other sites of disease; within 28 days prior to enrollment). To include bone 
scan if indicated by signs or symptoms 
 
Key Treatment and Follow-Up Procedures (see Section 7.3, 7.4, and 7.5 for a complete list): 
• 
Recording of adverse events and concomitant medications 
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including weight, and ECOG performance status  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
Samples for biomarkers and anti-AMG 479 antibodies  
• 
Samples for AMG 479, paclitaxel and carboplatin PK 
• 
Radiological imaging to assess disease extent will be performed every 6 weeks (±7 days) 
from study day 1 during the first 6 months of the study and then every 9 weeks (±7 days) 
thereafter, independent of the treatment cycle.  Radiological assessment must include CT 
scan or MRI of the chest and abdomen.  CT scan or MRI of the pelvis and all other site of 
disease will ONLY be assessed if positive at baseline and/or signs or symptoms suggestive 
of metastasis are present to confirm disease progression. The modality selected should be 
the same throughout the study.   
 
Statistical Considerations:  Overall safety will be evaluated for all subjects who received at 
least one dose of any study treatment component (AMG 479, paclitaxel, or carboplatin).  The 
primary analysis of the ORR will include Part 1 subjects who receive the final dose of AMG 479 
with paclitaxel/carboplatin and all Part 2 subjects in the full analysis set (10.2.4).  The interim 
analysis is planned to evaluate first 20 subjects enrolled in Part 2 and will evaluate safety and 
efficacy of the study regimen.  The study team, in consultation with participating investigator(s), 
may discontinue the study if the futility stopping rule is met. 
 
The combination of AMG 479 with paclitaxel/carboplatin may warrant further study if the posterior 
probability is at least 90% that the observed ORR exceeds that expected for the historical control 
of paclitaxel/carboplatin alone.  On the other hand, the study may suggest no further investigation 
of the combination is warranted if the posterior probability that the ORR is at least 20% higher 
than the historical ORR is less than 2.5%.  An observed ORR not meeting these criteria may be 
considered inconclusive.  All efficacy and safety outcomes will be considered in assessing the 
overall potential clinical benefit of the combination. 


Product:  AMG479 
Protocol Number:  20080257 
Date:  02-September-2008 
Page 8 of 114 
 
Study Design and Treatment Schema 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 1 of 158 
 
Title: A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and 
Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell 
Lung Cancer  
AMG 479 
Amgen Protocol Number 20080257 
 
Clinical Study Sponsor: 
Amgen Inc 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
Phone: 805-447-1000 
Key Sponsor Contact: 
Jesse McGreivy, MD 
Clinical Research Medical Director 
Amgen, Inc. 
1120 Veterans Blvd. 
ASF B3-3 
South San Francisco, CA 94080 
Phone: 650-244-2634 
Fax: 650-837-9716 
Email: jessem@amgen.com  
 
Nancy Kenyon 
Clinical Research Study Manager-U.S. 
Amgen, Inc. 
Mail Stop 38-2-B 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Phone: 805-447-5737 
Fax: 805-480-1291 
Email: nkenyon@amgen.com   
 
Lutfat Rahaman 
Clinical Research Study Manager-Outside U.S. 
Amgen, Inc. 
1 Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH  
UK 
Tel: +44 (0)1895 525496 
Fax: +44 (0) 1223 228 134 
Email:  
Amendment 1 Date: 
26-May-2009 
Date: 
02-September-2008 
 
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 sites: 1- 800-77-AMGEN 
For all other countries: 1-805-447-5000 
For all other study-related questions, continue to contact the Key Sponsor Contact. 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 2 of 158 
 
Investigator’s Agreement 
I have read the attached protocol entitled “A Phase 1b/ 2 Study of AMG 479 in 
Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced 
Squamous Non-Small Cell Lung Cancer” dated Amendment 1 26 May 2009, 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 Ethic Committee 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) 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 3 of 158 
 
Protocol Synopsis 
Title:  A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and Carboplatin for the 
First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer 
Study Phase:  1b/ 2 
Indication:  First-line advanced squamous Non-Small Cell Lung Cancer (NSCLC) 
Primary Objective:   
Part 1 (Phase 1b): To identify a dose of AMG 479 in combination with paclitaxel/carboplatin that 
can be administered safely and is tolerated as determined by the incidence of dose-limiting 
toxicity (DLT). 
Part 2 (Phase 2): To estimate the efficacy of AMG 479 (at the final dose selected in Part 1) in 
combination with paclitaxel/carboplatin as measured by the objective response rate (ORR) as per 
modified RECIST by investigator review. 
Secondary Objective(s):   
Part 1: 
To evaluate the safety and tolerability of de-escalating doses of AMG 479 in combination with 
paclitaxel/carboplatin in terms of the incidence of adverse events and laboratory abnormalities not 
defined as dose-limiting toxicities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Subjects who received the final dose in Part 1 will be included in the Part 2 efficacy and safety 
analysis. 
Part 2: 
To estimate the efficacy of AMG 479 in combination with paclitaxel/carboplatin as measured by 
progression free survival (PFS), time to progression (TTP), duration of response (DOR), 1 and 
2 year survival rates, and overall survival (including subjects who received the final dose in 
Part 1). 
To evaluate the safety and tolerability of AMG 479 in combination with paclitaxel/carboplatin in 
terms of the incidence of adverse events and laboratory abnormalities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Exploratory Objective(s):   
Parts 1 and 2: 
To evaluate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (optional; collect-and-hold approach). 
To correlate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST 
with pharmacodynamic measures (serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway). 
To investigate the genetic variation in drug metabolism genes, cancer genes, and drug target 
genes and correlate with outcomes related to AMG 479 in combination with paclitaxel/carboplatin 
therapy (requires a separate informed consent, optional for subjects). 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 4 of 158 
 
To investigate tumor tissue analysis of somatic gene mutations that function to regulate the 
IGF-1R pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available). 
To investigate mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens. This will include but will not be limited to 
analysis of PTEN expression by immunohistochemistry (if tissue is available). 
Hypotheses:   
In Part 1, AMG 479 can be given with paclitaxel/carboplatin at a safe and tolerated dose as 
determined by the incidence of DLTs. 
In Part 2, the ORR of AMG 479 in combination with paclitaxel/carboplatin will exceed that for the 
historical control of paclitaxel/carboplatin alone (See Section 10.3.2 for the weighted historical 
average). 
Study Design:  
Part 1 is an open-label, single arm dose de-escalation phase 1b segment to determine the safety 
and tolerability of AMG 479 in combination with paclitaxel/carboplatin every 3 weeks (Q3W) for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 as first-line 
therapy in advanced squamous NSCLC. 
Part 2 is a single arm open-label phase 2 segment in which AMG 479 in combination with 
paclitaxel/carboplatin Q3W for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 will be used to determine the efficacy and safety of this regimen.  
The dose of AMG 479 used in Part 2 will be based on the final dose of AMG 479 from Part 1. 
In Part 1, approximately 6 to 9 subjects will be enrolled in Cohort 1 to receive AMG 479 at 
18 mg/kg in combination with paclitaxel (200 mg/m2) and carboplatin (AUC 6) IV on day 1 every 
3 week cycle for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for up to 
24 months from study day 1.  Pending review of dose limiting toxicities from Cohort 1 by the study 
team, in consultation with participating investigator(s), a lower dose of AMG 479 at 12 mg/kg in 
combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg 
monotherapy for up to 24 months from study day 1 may be administered to an additional 6 to 
9 subjects in Cohort 2 (please see Section 3.1 Study Design for further clarification here). 
In Part 2, an additional 31 to 34 subjects will be treated with AMG 479 at the final dose from 
Part 1 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at the final 
dose from Part 1 monotherapy for up to 24 months from study day 1.  Part 2 will be open 
following the review of the Part 1 data by the study team, in consultation with participating 
investigator(s) as outlined in Section 3.1. 
In Part 1 and Part 2, AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter). 
In Part 1 and Part 2, all subjects receive AMG 479 in combination with paclitaxel/carboplatin for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 to be 
administered until progression of disease, intolerable adverse event, death, or withdrawal of 
consent. 
Radiological imaging to assess progressive disease (PD) 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. 
A follow-up visit 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 to assess disease and survival status for up to 36 months from the date of the 
last subject enrolled in the study.  Please refer to the Study Schema for an overview of the 2-part 
study design. 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 5 of 158 
 
Primary and Secondary Endpoints: 
Primary Endpoints: 
Part 1:  
• 
The incidence of adverse events and clinical laboratory abnormalities defined as 
dose-limiting toxicities 
Part 2:  
• 
ORR as per modified RECIST criteria by investigator review 
 
Secondary Endpoints 
Part 1: 
• 
The incidence of adverse events and laboratory abnormalities not defined as dose 
limiting toxicities 
• 
The incidence of anti-AMG 479 antibody formation 
Part 2: 
• 
PFS, TTP, DOR, 1 and 2 year survival rates, and OS including subjects who received the 
final dose in Part 1 
• 
The incidence of adverse events and laboratory abnormalities 
• 
The incidence of anti-AMG 479 antibody formation 
 
Part 1 and 2 (PK): 
• 
Cmax and Cmin for AMG 479 for all subjects 
• 
Cmax, C24 or AUC24 for paclitaxel and carboplatin in subjects with intensive sampling  
 
Exploratory Endpoints 
Part 1 and Part 2: 
• 
ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (this analysis is optional and may be initiated by the 
sponsor; all radiographic images from the study will be sent to a central imaging vendor 
with a collect-and-hold approach) 
• 
Pharmacodynamic response: serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway 
• 
Analysis of genetic variation (optional separate informed consent required)  
• 
Tumor tissue analysis of somatic gene mutations that function to regulate the IGF-1R 
pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available) 
• 
Analysis of mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens (if tissue is available). This will 
include but will not be limited to analysis of PTEN expression by immunohistochemistry. 
 
Sample Size:  Part 1: 6 to 18 subjects; Part 2: 31 to 34 subjects (see Section 9.3 Sample Size for 
rational) 
Summary of Subject Eligibility Criteria: See Section 3 for further details 
Key Inclusion Criteria 
• 
Histologically or cytologically confirmed advanced squamous NSCLC defined as stage 
IIIB with malignant effusion or stage IV or recurrent disease (recurrent disease is defined 
as documented disease progression following complete surgical resection for stage I or II 
disease).  Subjects with mixed tumors with squamous features are eligible unless small 
cell elements are present in which case the subject will be ineligible.  Cytologic or 
histologic elements can be established on metastatic tumor aspirates or biopsy. 
Confirmation must be prior to enrollment.   
• 
Measurable disease as defined per modified RECIST criteria (see Appendix F) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status of  0 or 1 
(see Appendix E) 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 6 of 158 
 
• 
≥18 years old 
• 
Glycosylated hemoglobin (HgbA1c) ≤ 8%   
Key Exclusion Criteria 
• 
Untreated or symptomatic central nervous system (CNS) metastases 
 
Subjects with a history of CNS metastases that are both definitively treated and 
stably controlled are eligible if all of the following apply: 1) definitive therapy has 
been administered (surgery and/or radiation therapy); 2) there is no additional 
treatment planned for brain metastases; 3) the subject is clinically stable; 4) the 
subject is off corticosteroids or on a stable dose of corticosteroids for at least 
14 days prior to enrollment. 
• 
Prior anti-cancer therapy as follows: 
 
Any prior chemotherapy for advanced squamous NSCLC 
 
Any prior adjuvant or neo-adjuvant chemotherapy for squamous NSCLC 
 
Any prior chemoradiation for squamous NSCLC 
 
Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for 
peripheral lesions ≤ 14 days prior to enrollment for squamous NSCLC 
• 
Currently or previously treated with biological, immunological or other therapies for 
squamous NSCLC 
 
Investigational Product Dosage (AMG 479) and Chemotherapy Administration: 
Part 1 (dose de-escalation design): 
• 
Cohort 1: AMG 479 18 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
18 mg/kg IV monotherapy for up to 24 months from study day 1 
• 
Cohort 2: AMG 479 12 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
12 mg/kg IV monotherapy for up to 24 months from study day 1 
Part 2:  
• 
AMG 479 IV in combination with paclitaxel 200 mg/m2 and carboplatin (AUC 6) IV on day 1 of 
every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 
24 months from study day 1.  The AMG 479 dose to be used in Part 2 will be the final 
AMG 479 dose explored from Part 1. 
For Part 1 and Part 2: AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter).  Moreover, for Part 1 and Part 2, AMG 479 will be given in combination 
with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 until progression of disease, intolerable adverse event, death, or 
withdrawal of consent. 
Procedures:  See Section 6.1 and Schedule of Assessments (Appendix A) for details. 
Key Screening Procedures (see Section 6.2 for a complete list): 
• 
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, weight, and ECOG performance status assessment  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  


Product:  AMG 479 
Protocol Number:  20080257 
Date:  26 May 2009 
Page 7 of 158 
 
• 
If available, submission of paraffin-embedded tumor tissue (paraffin tumor block, or slides) 
and all available pathology reports 
• 
12-lead electrocardiogram (ECG)  
• 
Radiological imaging to assess disease extent (CT scan or MRI of the brain, chest, abdomen, 
pelvis, and all other sites of disease; within 28 days prior to enrollment). To include bone 
scan if indicated by signs or symptoms 
 
Key Treatment and Follow-Up Procedures (see Section 6.3, 6.4, and 6.5 for a complete list): 
• 
Recording of adverse events and concomitant medications 
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including weight, and ECOG performance status  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
Samples for biomarkers and anti-AMG 479 antibodies  
• 
Samples for AMG 479, paclitaxel and carboplatin PK 
• 
Radiological imaging to assess disease extent will be performed every 6 weeks (± 7 days) 
from study day 1 during the first 6 months of the study and then every 9 weeks (± 7 days) 
thereafter, independent of the treatment cycle.  Radiological assessment must include CT 
scan or MRI of the chest and abdomen.  CT scan or MRI of the pelvis and all other site of 
disease will ONLY be assessed if positive at baseline and/or signs or symptoms suggestive 
of metastasis are present to confirm disease progression. The modality selected should be 
the same throughout the study.   
 
Statistical Considerations:  Overall safety will be evaluated for all subjects who received at 
least one dose of any study treatment component (AMG 479, paclitaxel, or carboplatin).  The 
primary analysis of the ORR will include Part 1 subjects who receive the final dose of AMG 479 
with paclitaxel/carboplatin and all Part 2 subjects in the full analysis set (Section 10.2.4).  The 
interim analysis is planned to evaluate first 20 subjects enrolled in Part 2 and will evaluate safety 
and efficacy of the study regimen.  The study team, in consultation with participating 
investigator(s), may discontinue the study if the futility stopping rule is met. 
 
The combination of AMG 479 with paclitaxel/carboplatin may warrant further study if the posterior 
probability is at least 90% that the observed ORR exceeds that expected for the historical control 
of paclitaxel/carboplatin alone.  On the other hand, the study may suggest no further investigation 
of the combination is warranted if the posterior probability that the ORR is at least 20% higher 
than the historical ORR is less than 2.5%.  An observed ORR not meeting these criteria may be 
considered inconclusive.  All efficacy and safety outcomes will be considered in assessing the 
overall potential clinical benefit of the combination. 


Product:  AMG 479 
Protocol Number:  20080257 
Date: 26 May 2009 
Page 8 of 158 
 
Study Design and Treatment Schema 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 1 of 159 
 
Title: A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and 
Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell 
Lung Cancer  
AMG 479 
Amgen Protocol Number 20080257 
 
Clinical Study Sponsor: 
Amgen Inc 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
Phone: 805-447-1000 
Key Sponsor Contact: 
Jesse McGreivy, MD 
Clinical Research Medical Director 
Amgen, Inc. 
1120 Veterans Blvd. 
ASF B3-3 
South San Francisco, CA 94080 
Phone: 650-244-2634 
Fax: 650-837-9716 
Email: jessem@amgen.com  
 
Nancy Kenyon 
Clinical Research Study Manager-U.S. 
Amgen, Inc. 
Mail Stop 38-2-B 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Phone: 805-447-5737 
Fax: 805-480-1291 
Email: nkenyon@amgen.com   
 
Lutfat Rahaman 
Clinical Research Study Manager-Outside U.S. 
Amgen, Inc. 
1 Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH  
UK 
Tel: +44 (0)1895 525496 
Fax: +44 (0) 1223 228 134 
Email:  
Superseding Date, Amendment 1
18-June-2009 
Amendment 1 Date: 
26-May-2009 
Original Protocol Date: 
02-September-2008 
 
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 sites: 1- 800-77-AMGEN 
For all other countries: 1-805-447-5000 
For all other study-related questions, continue to contact the Key Sponsor Contact. 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 2 of 159 
 
Investigator’s Agreement 
I have read the attached protocol entitled “A Phase 1b/ 2 Study of AMG 479 in 
Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced 
Squamous Non-Small Cell Lung Cancer”, Superseding Date 18-June-2009 
Amendment 1, 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 Ethic Committee 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) 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 3 of 159 
 
Protocol Synopsis 
Title:  A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and Carboplatin for the 
First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer 
Study Phase:  1b/ 2 
Indication:  First-line advanced squamous Non-Small Cell Lung Cancer (NSCLC) 
Primary Objective:   
Part 1 (Phase 1b): To identify a dose of AMG 479 in combination with paclitaxel/carboplatin that 
can be administered safely and is tolerated as determined by the incidence of dose-limiting 
toxicity (DLT). 
Part 2 (Phase 2): To estimate the efficacy of AMG 479 (at the final dose selected in Part 1) in 
combination with paclitaxel/carboplatin as measured by the objective response rate (ORR) as per 
modified RECIST by investigator review. 
Secondary Objective(s):   
Part 1: 
To evaluate the safety and tolerability of de-escalating doses of AMG 479 in combination with 
paclitaxel/carboplatin in terms of the incidence of adverse events and laboratory abnormalities not 
defined as dose-limiting toxicities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Subjects who received the final dose in Part 1 will be included in the Part 2 efficacy and safety 
analysis. 
Part 2: 
To estimate the efficacy of AMG 479 in combination with paclitaxel/carboplatin as measured by 
progression free survival (PFS), time to progression (TTP), duration of response (DOR), 1 and 
2 year survival rates, and overall survival (including subjects who received the final dose in 
Part 1). 
To evaluate the safety and tolerability of AMG 479 in combination with paclitaxel/carboplatin in 
terms of the incidence of adverse events and laboratory abnormalities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Exploratory Objective(s):   
Parts 1 and 2: 
To evaluate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (optional; collect-and-hold approach). 
To correlate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST 
with pharmacodynamic measures (serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway). 
To investigate the genetic variation in drug metabolism genes, cancer genes, and drug target 
genes and correlate with outcomes related to AMG 479 in combination with paclitaxel/carboplatin 
therapy (requires a separate informed consent, optional for subjects). 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 4 of 159 
 
To investigate tumor tissue analysis of somatic gene mutations that function to regulate the 
IGF-1R pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available). 
To investigate mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens.  This will include but will not be limited to 
analysis of PTEN expression by immunohistochemistry (if tissue is available). 
Hypotheses:   
In Part 1, AMG 479 can be given with paclitaxel/carboplatin at a safe and tolerated dose as 
determined by the incidence of DLTs. 
In Part 2, the ORR of AMG 479 in combination with paclitaxel/carboplatin will exceed that for the 
historical control of paclitaxel/carboplatin alone (See Section 10.3.2 for the weighted historical 
average). 
Study Design:  
Part 1 is an open-label, single arm dose de-escalation phase 1b segment to determine the safety 
and tolerability of AMG 479 in combination with paclitaxel/carboplatin every 3 weeks (Q3W) for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 as first-line 
therapy in advanced squamous NSCLC. 
Part 2 is a single arm open-label phase 2 segment in which AMG 479 in combination with 
paclitaxel/carboplatin Q3W for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 will be used to determine the efficacy and safety of this regimen.  
The dose of AMG 479 used in Part 2 will be based on the final dose of AMG 479 from Part 1. 
In Part 1, approximately 6 to 9 subjects will be enrolled in Cohort 1 to receive AMG 479 at 
18 mg/kg in combination with paclitaxel (200 mg/m2) and carboplatin (AUC 6) IV on day 1 every 
3 week cycle for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for up to 
24 months from study day 1.  Pending review of dose limiting toxicities from Cohort 1 by the study 
team, in consultation with participating investigator(s), a lower dose of AMG 479 at 12 mg/kg in 
combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg 
monotherapy for up to 24 months from study day 1 may be administered to an additional 6 to 
9 subjects in Cohort 2 (please see Section 3.1 Study Design for further clarification here). 
In Part 2, an additional 31 to 34 subjects will be treated with AMG 479 at the final dose from 
Part 1 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at the final 
dose from Part 1 monotherapy for up to 24 months from study day 1.  Part 2 will be open 
following the review of the Part 1 data by the study team, in consultation with participating 
investigator(s) as outlined in Section 3.1. 
In Part 1 and Part 2, AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter). 
In Part 1 and Part 2, all subjects receive AMG 479 in combination with paclitaxel/carboplatin for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 to be 
administered until progression of disease, intolerable adverse event, death, or withdrawal of 
consent. 
Radiological imaging to assess progressive disease (PD) 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. 
A follow-up visit 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 to assess disease and survival status for up to 36 months from the date of the 
last subject enrolled in the study.  Please refer to the Study Schema for an overview of the 2-part 
study design. 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 5 of 159 
 
Primary and Secondary Endpoints: 
Primary Endpoints: 
Part 1:  
• 
The incidence of adverse events and clinical laboratory abnormalities defined as 
dose-limiting toxicities 
Part 2:  
• 
ORR as per modified RECIST criteria by investigator review 
 
Secondary Endpoints 
Part 1: 
• 
The incidence of adverse events and laboratory abnormalities not defined as dose 
limiting toxicities 
• 
The incidence of anti-AMG 479 antibody formation 
Part 2: 
• 
PFS, TTP, DOR, 1 and 2 year survival rates, and OS including subjects who received the 
final dose in Part 1 
• 
The incidence of adverse events and laboratory abnormalities 
• 
The incidence of anti-AMG 479 antibody formation 
 
Part 1 and 2 (PK): 
• 
Cmax and Cmin for AMG 479 for all subjects 
• 
Cmax, C24 or AUC24 for paclitaxel and carboplatin in subjects with intensive sampling  
 
Exploratory Endpoints 
Part 1 and Part 2: 
• 
ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (this analysis is optional and may be initiated by the 
sponsor; all radiographic images from the study will be sent to a central imaging vendor 
with a collect-and-hold approach) 
• 
Pharmacodynamic response: serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway 
• 
Analysis of genetic variation (optional separate informed consent required)  
• 
Tumor tissue analysis of somatic gene mutations that function to regulate the IGF-1R 
pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available) 
• 
Analysis of mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens (if tissue is available).  This will 
include but will not be limited to analysis of PTEN expression by immunohistochemistry. 
 
Sample Size:  Part 1: 6 to 18 subjects; Part 2: 31 to 34 subjects (see Section10.3 Sample Size 
for rational) 
Summary of Subject Eligibility Criteria: See Section 4 for further details 
Key Inclusion Criteria 
• 
Histologically or cytologically confirmed advanced squamous NSCLC defined as stage 
IIIB with malignant effusion or stage IV or recurrent disease (recurrent disease is defined 
as documented disease progression following complete surgical resection for stage I or II 
disease).  Subjects with mixed tumors with squamous features are eligible unless small 
cell elements are present in which case the subject will be ineligible.  Cytologic or 
histologic elements can be established on metastatic tumor aspirates or biopsy.  
Confirmation must be prior to enrollment.   
• 
Measurable disease as defined per modified RECIST criteria (see Appendix F) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status of  0 or 1 
(see Appendix E) 


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 6 of 159 
 
• 
≥18 years old 
• 
Glycosylated hemoglobin (HgbA1c) ≤ 8%   
Key Exclusion Criteria 
• 
Untreated or symptomatic central nervous system (CNS) metastases 
 
Subjects with a history of CNS metastases that are both definitively treated and 
stably controlled are eligible if all of the following apply: 1) definitive therapy has 
been administered (surgery and/or radiation therapy); 2) there is no additional 
treatment planned for brain metastases; 3) the subject is clinically stable; 4) the 
subject is off corticosteroids or on a stable dose of corticosteroids for at least 
14 days prior to enrollment. 
• 
Prior anti-cancer therapy as follows: 
 
Any prior chemotherapy for advanced squamous NSCLC 
 
Any prior adjuvant or neo-adjuvant chemotherapy for squamous NSCLC 
 
Any prior chemoradiation for squamous NSCLC 
 
Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for 
peripheral lesions ≤ 14 days prior to enrollment for squamous NSCLC 
• 
Currently or previously treated with biological, immunological or other therapies for 
squamous NSCLC 
 
Investigational Product Dosage (AMG 479) and Chemotherapy Administration: 
Part 1 (dose de-escalation design): 
• 
Cohort 1: AMG 479 18 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
18 mg/kg IV monotherapy for up to 24 months from study day 1 
• 
Cohort 2: AMG 479 12 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
12 mg/kg IV monotherapy for up to 24 months from study day 1 
Part 2:  
• 
AMG 479 IV in combination with paclitaxel 200 mg/m2 and carboplatin (AUC 6) IV on day 1 of 
every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 
24 months from study day 1.  The AMG 479 dose to be used in Part 2 will be the final 
AMG 479 dose explored from Part 1. 
For Part 1 and Part 2: AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter).  Moreover, for Part 1 and Part 2, AMG 479 will be given in combination 
with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 until progression of disease, intolerable adverse event, death, or 
withdrawal of consent. 
Procedures:  See Section 7.1and Schedule of Assessments (Appendix A) for details. 
Key Screening Procedures (see Section 7.2 for a complete list): 
• 
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, weight, and ECOG performance status assessment  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  


Product:  AMG 479 
Protocol Number:  20080257 
Date:  18 June 2009 
Page 7 of 159 
 
• 
If available, submission of paraffin-embedded tumor tissue (paraffin tumor block, or slides) 
and all available pathology reports 
• 
12-lead electrocardiogram (ECG)  
• 
Radiological imaging to assess disease extent (CT scan or MRI of the brain, chest, abdomen, 
pelvis, and all other sites of disease; within 28 days prior to enrollment).  To include bone 
scan if indicated by signs or symptoms 
 
Key Treatment and Follow-Up Procedures (see Section 7.3, 7.4, and 7.5 for a complete list): 
• 
Recording of adverse events and concomitant medications 
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including weight, and ECOG performance status  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
Samples for biomarkers and anti-AMG 479 antibodies  
• 
Samples for AMG 479, paclitaxel and carboplatin PK 
• 
Radiological imaging to assess disease extent will be performed every 6 weeks (± 7 days) 
from study day 1 during the first 6 months of the study and then every 9 weeks (± 7 days) 
thereafter, independent of the treatment cycle.  Radiological assessment must include CT 
scan or MRI of the chest and abdomen.  CT scan or MRI of the pelvis and all other site of 
disease will ONLY be assessed if positive at baseline and/or signs or symptoms suggestive 
of metastasis are present to confirm disease progression.  The modality selected should be 
the same throughout the study.   
 
Statistical Considerations:  Overall safety will be evaluated for all subjects who received at 
least one dose of any study treatment component (AMG 479, paclitaxel, or carboplatin).  The 
primary analysis of the ORR will include Part 1 subjects who receive the final dose of AMG 479 
with paclitaxel/carboplatin and all Part 2 subjects in the full analysis set (Section 10.2.4).  The 
interim analysis is planned to evaluate first 20 subjects enrolled in Part 2 and will evaluate safety 
and efficacy of the study regimen.  The study team, in consultation with participating 
investigator(s), may discontinue the study if the futility stopping rule is met. 
 
The combination of AMG 479 with paclitaxel/carboplatin may warrant further study if the posterior 
probability is at least 90% that the observed ORR exceeds that expected for the historical control 
of paclitaxel/carboplatin alone.  On the other hand, the study may suggest no further investigation 
of the combination is warranted if the posterior probability that the ORR is at least 20% higher 
than the historical ORR is less than 2.5%.  An observed ORR not meeting these criteria may be 
considered inconclusive.  All efficacy and safety outcomes will be considered in assessing the 
overall potential clinical benefit of the combination. 


Product:  AMG 479 
Protocol Number:  20080257 
Date: 18-June-2009 
Page 8 of 159 
 
Study Design and Treatment Schema 


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 1 of 135 
 
Title: A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and 
Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell 
Lung Cancer  
AMG 479 
Amgen Protocol Number 20080257 
 
Clinical Study Sponsor: 
Amgen Inc 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
Phone: 805-447-1000 
Key Sponsor Contact: 
Jesse McGreivy, MD 
Clinical Research Medical Director 
Amgen, Inc. 
1120 Veterans Blvd. 
ASF B3-3 
South San Francisco, CA 94080 
Phone: 650-244-2634 
Fax: 650-837-9716 
Email: jessem@amgen.com  
 
Nancy Kenyon 
Clinical Research Study Manager-U.S. 
Amgen, Inc. 
Mail Stop 38-2-B 
One Amgen Center Drive 
Thousand Oaks, CA 91320-1799 
Phone: 805-447-5737 
Fax: 805-480-1291 
Email: nkenyon@amgen.com   
 
Kay Smith 
Clinical Research Study Manager-Outside U.S. 
Amgen, Inc. 
240 Milton Road (Cambridge Science Park)  
Cambridge  
UK 
Tel: +44 1223 420 305 
Fax: +44 (0) 1223 423 049 
Email:  
Amendment 2 
06-August-2010 
Superseding Date, Amendment 1 
18-June-2009 
Amendment 1 Date: 
26-May-2009 
Original Protocol Date: 
02-September-2008 
 
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 sites: 1- 800-77-AMGEN 
For all other countries: 1-805-447-5000 
For all other study-related questions, continue to contact the Key Sponsor Contact. 


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 2 of 135 
 
Investigator’s Agreement 
I have read the attached protocol entitled “A Phase 1b/ 2 Study of AMG 479 in 
Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced 
Squamous Non-Small Cell Lung Cancer”, Amendment 2, Date 06 August 2010, 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 Ethic Committee 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 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 3 of 135 
 
Protocol Synopsis 
Title:  A Phase 1b/ 2 Study of AMG 479 in Combination with Paclitaxel and Carboplatin for the 
First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer 
Study Phase:  1b/ 2 
Indication:  First-line advanced squamous Non-Small Cell Lung Cancer (NSCLC) 
Primary Objective:   
Part 1 (Phase 1b): To identify a dose of AMG 479 in combination with paclitaxel/carboplatin that 
can be administered safely and is tolerated as determined by the incidence of dose-limiting 
toxicity (DLT). 
Part 2 (Phase 2): To estimate the efficacy of AMG 479 (at the final dose selected in Part 1) in 
combination with paclitaxel/carboplatin as measured by the objective response rate (ORR) as per 
modified RECIST by investigator review. 
Secondary Objective(s):   
Part 1: 
To evaluate the safety and tolerability of de-escalating doses of AMG 479 in combination with 
paclitaxel/carboplatin in terms of the incidence of adverse events and laboratory abnormalities not 
defined as dose-limiting toxicities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Subjects who received the final dose in Part 1 will be included in the Part 2 efficacy and safety 
analysis. 
Part 2: 
To estimate the efficacy of AMG 479 in combination with paclitaxel/carboplatin as measured by 
progression free survival (PFS), time to progression (TTP), and duration of response (DOR), 
(including subjects who received the final dose in Part 1). 
To evaluate the safety and tolerability of AMG 479 in combination with paclitaxel/carboplatin in 
terms of the incidence of adverse events and laboratory abnormalities. 
To evaluate the pharmacokinetics of AMG 479 and paclitaxel/carboplatin and estimate the impact 
of co-administration of AMG 479 on the pharmacokinetics of paclitaxel/carboplatin. 
To evaluate anti-AMG 479 antibody formation. 
Exploratory Objective(s):   
Parts 1 and 2: 
To evaluate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (optional; collect-and-hold approach). 
To correlate the ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST 
with pharmacodynamic measures (serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway). 
To investigate the genetic variation in drug metabolism genes, cancer genes, and drug target 
genes and correlate with outcomes related to AMG 479 in combination with paclitaxel/carboplatin 
therapy (requires a separate informed consent, optional for subjects). 


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 4 of 135 
 
To investigate tumor tissue analysis of somatic gene mutations that function to regulate the 
IGF-1R pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available). 
To investigate mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens.  This will include but will not be limited to 
analysis of PTEN expression by immunohistochemistry (if tissue is available). 
Hypotheses:   
In Part 1, AMG 479 can be given with paclitaxel/carboplatin at a safe and tolerated dose as 
determined by the incidence of DLTs. 
In Part 2, the ORR of AMG 479 in combination with paclitaxel/carboplatin will exceed that for the 
historical control of paclitaxel/carboplatin alone (See Section 10.3.2 for the weighted historical 
average). 
Study Design:  
Part 1 is an open-label, single arm dose de-escalation phase 1b segment to determine the safety 
and tolerability of AMG 479 in combination with paclitaxel/carboplatin every 3 weeks (Q3W) for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 as first-line 
therapy in advanced squamous NSCLC. 
Part 2 is a single arm open-label phase 2 segment in which AMG 479 in combination with 
paclitaxel/carboplatin Q3W for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 will be used to determine the efficacy and safety of this regimen.  
The dose of AMG 479 used in Part 2 will be based on the final dose of AMG 479 from Part 1. 
In Part 1, approximately 6 to 9 subjects will be enrolled in Cohort 1 to receive AMG 479 at 
18 mg/kg in combination with paclitaxel (200 mg/m2) and carboplatin (AUC 6) IV on day 1 every 
3 week cycle for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for up to 
24 months from study day 1.  Pending review of dose limiting toxicities from Cohort 1 by the study 
team, in consultation with participating investigator(s), a lower dose of AMG 479 at 12 mg/kg in 
combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 12 mg/kg 
monotherapy for up to 24 months from study day 1 may be administered to an additional 6 to 
9 subjects in Cohort 2 (please see Section 3.1 Study Design for further clarification here). 
In Part 2, an additional 31 to 34 subjects will be treated with AMG 479 at the final dose from 
Part 1 in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at the final 
dose from Part 1 monotherapy for up to 24 months from study day 1.  Part 2 will be open 
following the review of the Part 1 data by the study team, in consultation with participating 
investigator(s) as outlined in Section 3.1. 
In Part 1 and Part 2, AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter). 
In Part 1 and Part 2, all subjects receive AMG 479 in combination with paclitaxel/carboplatin for 
4 to 6 cycles followed by AMG 479 monotherapy for up to 24 months from study day 1 to be 
administered until progression of disease, intolerable adverse event, death, or withdrawal of 
consent. 
Radiological imaging to assess progressive disease (PD) 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. 
A follow-up visit will occur 30 (+ 7) days and 60 (+ 14) days after the last dose of 
protocol-specified treatment.  Please refer to the Study Schema for an overview of the 2-part 
study design. 


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 5 of 135 
 
Primary and Secondary Endpoints: 
Primary Endpoints: 
Part 1:  
• 
The incidence of adverse events and clinical laboratory abnormalities defined as 
dose-limiting toxicities 
Part 2:  
• 
ORR as per modified RECIST criteria by investigator review 
 
Secondary Endpoints 
Part 1: 
• 
The incidence of adverse events and laboratory abnormalities not defined as dose 
limiting toxicities 
• 
The incidence of anti-AMG 479 antibody formation 
Part 2: 
• 
PFS, TTP and DOR, including subjects who received the final dose in Part 1 
• 
The incidence of adverse events and laboratory abnormalities 
• 
The incidence of anti-AMG 479 antibody formation 
 
Part 1 and 2 (PK): 
• 
Cmax and Cmin for AMG 479 for all subjects 
• 
Cmax, C24 or AUC24 for paclitaxel and carboplatin in subjects with intensive sampling  
 
Exploratory Endpoints 
Part 1 and Part 2: 
• 
ORR and other efficacy endpoints (DOR, PFS, TTP) as per modified RECIST by 
independent radiographic review (this analysis is optional and may be initiated by the 
sponsor; all radiographic images from the study will be sent to a central imaging vendor 
with a collect-and-hold approach) 
• 
Pharmacodynamic response: serum IGF-1, IGF-BP3, growth hormone, and other factors 
that are involved in regulating the IGF-1/IGF-1R pathway 
• 
Analysis of genetic variation (optional separate informed consent required)  
• 
Tumor tissue analysis of somatic gene mutations that function to regulate the IGF-1R 
pathway and other genes that are known to be involved in the development and 
progression of solid tumors (if tissue is available) 
• 
Analysis of mRNA and protein expression of genes that are known to regulate the 
IGF-1/IGF-1R pathway in archival tumor specimens (if tissue is available).  This will 
include but will not be limited to analysis of PTEN expression by immunohistochemistry. 
 
Sample Size:  Fourteen total subjects received AMG 479 in combination with 
paclitaxel/carboplatin, 6 subjects in Part 1 and 8 subjects in Part 2.  
Summary of Subject Eligibility Criteria: See Section 4 for further details 
Key Inclusion Criteria 
• 
Histologically or cytologically confirmed advanced squamous NSCLC defined as stage 
IIIB with malignant effusion or stage IV or recurrent disease (recurrent disease is defined 
as documented disease progression following complete surgical resection for stage I or II 
disease).  Subjects with mixed tumors with squamous features are eligible unless small 
cell elements are present in which case the subject will be ineligible.  Cytologic or 
histologic elements can be established on metastatic tumor aspirates or biopsy.  
Confirmation must be prior to enrollment.   
• 
Measurable disease as defined per modified RECIST criteria (see Appendix F) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status of  0 or 1 
(see Appendix E) 


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 6 of 135 
 
• 
≥18 years old 
• 
Glycosylated hemoglobin (HgbA1c) ≤ 8%   
Key Exclusion Criteria 
• 
Untreated or symptomatic central nervous system (CNS) metastases 
 
Subjects with a history of CNS metastases that are both definitively treated and 
stably controlled are eligible if all of the following apply: 1) definitive therapy has 
been administered (surgery and/or radiation therapy); 2) there is no additional 
treatment planned for brain metastases; 3) the subject is clinically stable; 4) the 
subject is off corticosteroids or on a stable dose of corticosteroids for at least 
14 days prior to enrollment. 
• 
Prior anti-cancer therapy as follows: 
 
Any prior chemotherapy for advanced squamous NSCLC 
 
Any prior adjuvant or neo-adjuvant chemotherapy for squamous NSCLC 
 
Any prior chemoradiation for squamous NSCLC 
 
Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for 
peripheral lesions ≤ 14 days prior to enrollment for squamous NSCLC 
• 
Currently or previously treated with biological, immunological or other therapies for 
squamous NSCLC 
 
Investigational Product Dosage (AMG 479) and Chemotherapy Administration: 
Part 1 (dose de-escalation design): 
• 
Cohort 1: AMG 479 18 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
18 mg/kg IV monotherapy for up to 24 months from study day 1 
• 
Cohort 2: AMG 479 12 mg/kg IV in combination with paclitaxel 200 mg/m2 and carboplatin 
(AUC 6) IV on day 1 of every 3 week cycle for 4 to 6 cycles, followed by AMG 479 at 
12 mg/kg IV monotherapy for up to 24 months from study day 1 
Part 2:  
• 
AMG 479 IV in combination with paclitaxel 200 mg/m2 and carboplatin (AUC 6) IV on day 1 of 
every 3 week cycle for 4 to 6 cycles, followed by AMG 479 IV monotherapy for up to 
24 months from study day 1.  The AMG 479 dose to be used in Part 2 will be the final 
AMG 479 dose explored from Part 1. 
For Part 1 and Part 2: AMG 479 will be dosed on day 1 of every 3 week cycle (except for subjects 
being evaluated by intensive PK who will receive AMG 479 on day 2 of cycle 1 and then on day 1 
of each cycle thereafter).  Moreover, for Part 1 and Part 2, AMG 479 will be given in combination 
with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 monotherapy for up to 
24 months from study day 1 until progression of disease, intolerable adverse event, death, or 
withdrawal of consent. 
Procedures:  See Section 7.1and Schedule of Assessments (Appendix A) for details. 
Key Screening Procedures (see Section 7.2 for a complete list): 
• 
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, weight, and ECOG performance status assessment  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  


Approved 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date:  06 August 2010 
Page 7 of 135 
 
• 
If available, submission of paraffin-embedded tumor tissue (paraffin tumor block, or slides) 
and all available pathology reports 
• 
12-lead electrocardiogram (ECG)  
• 
Radiological imaging to assess disease extent (CT scan or MRI of the brain, chest, abdomen, 
pelvis, and all other sites of disease; within 28 days prior to enrollment).  To include bone 
scan if indicated by signs or symptoms 
 
Key Treatment and Follow-Up Procedures (see Section 7.3, 7.4, and 7.5 for a complete list): 
• 
Recording of adverse events and concomitant medications 
• 
Vital signs: resting pulse, respiration, blood pressure, and temperature  
• 
Physical examination, including weight, and ECOG performance status  
• 
Laboratory tests: including hematology, chemistry, coagulation, urinalysis, pregnancy test  
• 
Samples for biomarkers and anti-AMG 479 antibodies  
• 
Samples for AMG 479, paclitaxel and carboplatin PK 
• 
Radiological imaging to assess disease extent will be performed every 6 weeks (± 7 days) 
from study day 1 during the first 6 months of the study and then every 9 weeks (± 7 days) 
thereafter, independent of the treatment cycle.  Radiological assessment must include CT 
scan or MRI of the chest and abdomen.  CT scan or MRI of the pelvis and all other site of 
disease will ONLY be assessed if positive at baseline and/or signs or symptoms suggestive 
of metastasis are present to confirm disease progression.  The modality selected should be 
the same throughout the study.   
 
Statistical Considerations:  Overall safety will be evaluated for all subjects who received at 
least one dose of any study treatment component (AMG 479, paclitaxel, or carboplatin).  The 
primary analysis of the ORR will include Part 1 subjects who receive the final dose of AMG 479 
with paclitaxel/carboplatin and all Part 2 subjects in the full analysis set (Section 10.2.4).  Given 
that enrollment was closed after 14 subjects were enrolled in both Part 1 and Part 2, 
neither the interim nor the primary analysis will occur.  Only the final analysis will be 
performed at the end of study which will occur when all subjects have had the opportunity 
to complete the 60 day follow up visit, or all subjects have died, or 26 months after the 
date the last subject was randomized, whichever date is earlier. 


 
Approved 
 
 
 
Product:  AMG 479 
Protocol Number:  20080257 
Date: 06 August 2010 
Page 8 of 135 
 
Study Design and Treatment Schema