This study was funded by Amgen Inc. Interim results from PACCE: irinotecan (Iri)/bevacizumab (bev) ± panitumumab (pmab) as first-line treatment (tx) for metastatic colorectal cancer (mCRC) J. Randolph Hecht,1 Edith Mitchell,2 Tarek Chidiac,3 Carroll Scroggin,4 Christopher Hagenstad,5 David Spigel,6 John Marshall,7 Allen Cohn,8 Sam Suzuki,9 Thomas Griffin9 1UCLA School of Medicine, Los Angeles, CA; 2Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA; 3Mid Ohio Oncology/Hematology, Inc, Columbus, OH; 4NEA clinic, Jonesboro, AR; 5Suburban Hematology-Oncology Associates, Lawrenceville, GA; 6Sarah Cannon Research Institute, Nashville, TN; 7Georgetown University Hospital, Washington, DC; 8Rocky Mountain Cancer Centers, Denver, CO; 9Amgen Inc., Thousand Oaks, CA This study was funded by Amgen Inc.

Introduction Panitumumab is a fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFr) and is approved as monotherapy in the US for the treatment of refractory mCRC Early studies have suggested that combining EGFr, VEGF inhibitors, and chemotherapy may improve efficacy1,2 PACCE was a US, community-based study designed to compare the efficacy and safety of bevacizumab and chemotherapy +/- panitumumab as first-line treatment for mCRC This is an interim analysis for data available as of May 31, 2007 describing the safety and efficacy for the Iri-CT based cohort from PACCE (trial discontinued only panitumumab therapy in March 2007 after a planned interim analysis of ~231 PFS events in the Ox-CT cohort) 1Shaheen et al. Brit J Cancer 2001;85:584-589 2Saltz LB et al. ASCO 2005. Abstract #3508 (BOND2)

PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study Schema PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Randomized, Open-Label, Controlled Phase 3b Trial Panitumumab 6 mg/kg Q2W + Ox-CT Bevacizumab Ox-based CT (eg, FOLFOX) N = 800 Inv choice S C R E N I G R A N D O M I Z E 1:1 Ox-CT + Bevacizumab Panitumumab 6 mg/kg Q2W + Iri-CT + Bevacizumab Iri-basedCT (eg, FOLFIRI) N = 200 Inv choice 1:1 Iri-CT + Bevacizumab Stratification Factors: ECOG score, prior adjuvant tx, disease site, Ox doses/Iri regimen, number of metastatic organs Tumor assessments: Q12W until disease progression or intolerability

Investigator Choice – Iri-CT Regimens Irinotecan Leucovorin (LV) 5-Fluorouracil (5-FU) FOLFIRI 180 mg/m2 IV over 90 min on Day1 per cycle 200 mg/m2 IV over 2 hrs on Day1 400 mg/m2 IV bolus over 2-4 min, followed 2400mg/m2 continuous IV over 46 hrs for the first 2 cycles, increased to 3000 mg/m2 if no toxicity >grade 1 Douillard 180 mg/m2 IV over 2 hrs on Day1 per cycle 200 mg/m2 IV over 2 hrs on Day1 and 2 400 mg/m2 IV bolus over 2-4 min, followed by 600 mg/m2 continuous IV over 22 hrs Day 1 and Day 2 Other Iri-CT Q2W TBD by physician

Key Eligibility Criteria Age ³ 18 years old Measurable mCRC per modified RECIST criteria ECOG status 0 or 1 Adequate hematologic, renal, and hepatic function No prior chemotherapy or biologic therapy for mCRC No adjuvant chemotherapy within 6 months No major surgery within 28 days of randomization or elective and/or planned major surgical procedures during the trial No clinically significant cardiovascular disease within 1 year prior to randomization No EGFr testing required

Study Endpoints and Design Characteristics Primary endpoint of the PACCE study:* Progression-free survival (PFS) by central review in the Ox-CT cohort To detect a 30% improvement in median PFS in the panitumumab plus bev/Ox-CT vs the bev/Ox-CT Planned interim analysis at ~231 Ox-CT PFS events Iri-CT cohort analyses were descriptive only Safety Efficacy including: Overall response rate (central and local review) PFS (central and local review), TTF, OS Exploratory biomarker analyses (eg, KRAS) *Powered for oxaliplatin cohort only; descriptive for irinotecan cohort

Treatment: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+ bev/Iri-CT (N=115) bev/Iri-CT (N=115) Patients randomized, n (%) 115 (100) Patients received any first-line treatment, n (%) 112 (97) Median follow-up, weeks Range 37.6 1.1 - 104.6 40.3 1.1 - 104.3 Chemotherapy regimen received on week 1, n (%)a FOLFIRI 97 (87) 104 (93) Douillard 9 ( 8) 3 ( 3) Other Iri-CT 6 ( 5) 5 ( 4) aOf those who received any first-line treatment

Baseline Demographics and Characteristics: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+ bev/Iri-CT (N=115) bev/Iri-CT (N=115) Male, % 49 62 Race, % White Black Hispanic Other 75 16 5 4 74 14 12 0 Median age (range), years 60.0 (35 – 84) 59.0 (23 – 80) Age  65, % 38 28 Baseline ECOG, % 0 1 59 41 64 36 Prior Adjuvant Therapy, % 33 31 Metastatic organs, % 1 >1 40 60 46 54

Summary of Adverse Events: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+ bev/Iri-CT (N=111) bev/Iri-CT (N=113) Any event, % 99 100 Grade 3 56 43 Grade 4 23 15 Grade 5* 5 1 Pmab-related grade 5 2 n/a Any serious (SAE), % 54 33 Ended all first-line treatment due to AE, % 17 Ended panitumumab treatment due to AE, % Panitumumab treatment-related SAE, % 16 AEs as reported by investigator Safety set included all patients who were dosed. Graded per NCI CTCAE v3.0 *As reported by investigator – does not include disease progression (ie, neoplasms); n/a= not applicable

Grade 3 or 4 Adverse Events of Interest: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+bev/Iri-CT (N=111) bev/Iri-CT (N=113) Grade 3 n (%) Grade 4 n (%) Skin toxicitya 41 ( 37) 0 (0) Diarrhea 30 (27) 1 (1) 10 (9) Neutropenia 16 (14) 3 (3) 19 (17) 5 (4) Dehydration 15 (14) 7 (6) Infectionsb 13 (12) 2 (2) Nausea 11 (10) Hypokalemia Vomiting 9 (8) 8 (7) Paronychia 4 (4) Hypomagnesemia Hypertension Deep venous thrombosis 14 (13) Pulmonary embolismc 12 (11) 6 (5) MedDRA v 9.0 preferred terms; graded per NCI CTCAE v 3.0 aSkin toxicity included multiple terms from the skin and subcutaneous and infections system organ class (SOC) bGrade 5 infections occurred in 2 (2%) pmab + bev/Iri-CT pts cGrade 5 pulmonary embolism occurred in 1 (1%) pmab + bev/Iri-CT pts Grade 5 gastrointestinal perforations occurred in 2 (2%) pmab + bev/Iri-CT pts

Overall Response Rate: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) Central Reviewa Local Reviewa pmab+ bev/Iri-CT (N=115) bev/Iri-CT (N=115) Best ORR 43% 39% 55% 46% Complete response 0% 10% 6% Partial response 44% 40% Stable disease 27% 38% 23% 30% Progressive diseaseb 13% 3% 5% Not done/Unevaluablec 17% 19% 15% aCT scans performed Q12W; responses did not require confirmation bCentral review unable to evaluate clinical disease progression (ie, non-radiographic PD); central review unable to accurately evaluate PD after surgical resections cIncluded missing and unreadable scans

Interim PFS – Iri-CT Cohort (May 2007 Data Cutoff) Central Reviewa Local Reviewb # PFS events (%) Median (95%CI), mos 54 (47) 10.1 (8.2, 13.7) 43 (37) 11.7 (9.0, 13.2) # PFS events (%) Median (95%CI), mos 62 (54) 11.0 (9.1, 13.6) 53 (46) 10.7 (9.0, 12.5) Pmab+bev/Iri-CT Bev/Iri-CT HR= 1.21 (95% CI: 0.80, 1.82)* HR= 0.92 (95% CI: 0. (0.63, 1.34)* *Descriptive only *Descriptive only 0% 20% 40% 60% 80% 100% 5 10 15 20 25 0% 20% 40% 60% 80% 100% 5 10 15 20 25 Months Central vs local review background: Original primary endpoint was PFS by local review; Protocol amended in May 2006 to primary endpoint by central review Central review in PACCE protocol is not a typical phase 3 mCRC central review process: - single radiologist read, no oncologist review - clinical (non-radiographic) disease progression unable to be evaluated by central review CT scans were performed every 12-weeks in PACCE (typically Ph3 mCRC studies are every 8 weeks) 2) Differences in censoring rules for central and local - Central censoring: if endpoint not reached and there were no further scans, pt was censored back to their last scan date (Q12W) - Local censoring: if endpoint not reached and there were no further scans, pt was censored back to their last investigator contact (Q2W) Bev/Iri-CT cohort had more censoring than pmab+bev/Iri-CT cohort in both central and local reviews Central review unable to assess disease progression after surgical resections Per the PACCE protocol, central review is unable to accurately evaluate patients’ disease progression after surgery Potential investigator bias for local review Months Pmab 115 74 23 7 1 115 86 33 7 2 Censored 19 32 6 4 9 31 11 1 1 No Pmab 115 76 23 6 1 115 85 27 6 Censored 29 34 7 2 14 34 11 3 aCensoring based on last available scan read centrally Q12W bCensoring based on last day of patient contact or visit Q2W Central vs Local Review Differences in censoring rules; more early censoring in central review and in bev/Iri-CT cohort Central review unable to assess clinical disease progression Central review unable to accurately evaluate PD after surgical resections Investigator bias

PFS - Differences Between Central vs Local Review Differences in censoring rules Central censoring: if endpoint not reached, pt was censored back to their last scan date (Q12W) Local censoring: if endpoint not reached, pt was censored back to their last investigator contact (Q2W on treatment, Q12W post-treatment follow-up) More early censoring in central review and in bev/Iri-CT cohort Central review unable to assess clinical disease progression Per protocol, central review defined as single radiologist read, no oncologist review Central review unable to accurately evaluate PD after surgical resections Potential investigator bias for local review Central vs local review background: Original primary endpoint was PFS by local review; Protocol amended in May 2006 to primary endpoint by central review Central review in PACCE protocol is not a typical phase 3 mCRC central review process: - single radiologist read, no oncologist review - clinical (non-radiographic) disease progression unable to be evaluated by central review CT scans were performed every 12-weeks in PACCE (typically Ph3 mCRC studies are every 8 weeks) 2) Differences in censoring rules for central and local - Central censoring: if endpoint not reached and there were no further scans, pt was censored back to their last scan date (Q12W) - Local censoring: if endpoint not reached and there were no further scans, pt was censored back to their last investigator contact (Q2W) Bev/Iri-CT cohort had more censoring than pmab+bev/Iri-CT cohort in both central and local reviews Central review unable to assess disease progression after surgical resections Per the PACCE protocol, central review is unable to accurately evaluate patients’ disease progression after surgery Potential investigator bias for local review

Other Efficacy Endpoints: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+ bev/Iri-CT (N=115) bev/Iri-CT (N=115) Time to Treatment Failure, Median (95% CI), months 6.6 (5.9 - 8.0) 6.0 (4.8 - 6.9) Overall Survival, Median (95% CI), months 20.7 (17.8 - NE) 20.5 (19.8 - NE) Deaths events, n (%)a 26 (23) 18 (16) Within 60 days of first dose, n (%) 5 ( 4) 2 ( 2) Within 30 days of last dose of 1st line tx, n (%) 8 ( 7) 3 ( 3) aDeaths at any time including long-term follow-up (post-study treatment) NE= not evaluable

Reasons for First-Line Treatment Discontinuation: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab + bev/Iri-CT (N=115) bev/Iri-CT (N=115) Patients discontinued first-line tx, n (%) 102 (89) 99 (86) Progressive events, n (%)a 42 (41) 29 (29) Disease progression 36 (35) 27 (27) Deaths 6 (6) 2 (2) Non-progressive events, n (%)a 60 (59) 70 (71) Adverse events 17 (17) Protocol violation 3 (3) 5 (5) Consent withdrawn/ refused treatment 15 (15) 26 (26) Otherb 25 (25) 33 (33) aOf those who discontinued first-line treatment bOther included end of first-line treatment without progression, requirement for alternative therapy, administrative, lost to follow-up, and other

Relative Dose Intensity Treatment Exposure: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) Dose Delays % Pts Dose Reductions % Pts Relative Dose Intensity (RDI) %   pmab+ bev/Iri n=111 bev/Iri n=113 pmab+ bev/Iri n=111 bev/Iri N=113 Panitumumab 65 n/a 34 83 Bevacizumab 61 45 1 3 88 92 Irinotecan 63 46 21 18 81 5-FU 61a 45a 24a 16a 81b 87b % Pts Inf 5-FU/ Iri/Bev ≥ 85% 44 aBolus 5-FU bInfusional 5-FU n/a=not applicable

Prevalence of Mutant KRAS: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff) pmab+ bev/Iri-CT bev/Iri-CT Patients randomized, n 115 KRAS not tested, n (%) 6 (5) 8 (7) KRAS tests failed, n (%) 3 (3) 9 (8) Did not receive treatment, n (%) 1 (1) Patients included in KRAS analysis, n (%) 103 (90) 97 (84) Patients included in KRAS analysis, n 103 97 Wild-type KRAS, n (%) 57 (55) 58 (60) Mutant KRAS, n (%) 46 (45) 39 (40)

pmab+ bev/Iri-CT (n/N) % Overall Response Rate By KRAS Status (Interim Analysis, May 2007 Data Cutoff) Central Review N pmab+ bev/Iri-CT (n/N) % bev/Iri-CT (n/N) % Odds Ratioa (95% CI) Wild-type KRAS 115 31/57 (54) 27/58 (47) 1.42 (0.63-3.21) Mutant KRAS 85 14/46 (30) 15/39 (38) 0.59 (0.23-1.55) KRAS efficacy set 200 45/103 (44) 42/97 (43) 1.00 (0.56-1.80) Iri-CT ITT set 230 49/115 (43) 45/115 (39) 1.15 (0.67-1.98) Local Review 40/57 (70) 34/58 (59) 1.71 (0.75-3.88) 19/46 (41) 17/39 (44) 0.81 (0.32-2.05) 59/103 (57) 51/97 (53) 1.28 (0.71-2.29) 63/115 (55) 53/115 (46) 1.45 (0.85-2.46) aOdds ratio for pmab:control (greater than 1.0 favors pmab+bev/Iri-CT). Descriptive only

SUMMARY This is a descriptive interim analysis of bev/Iri-CT +/- panitumumab in the PACCE study Response rates were higher in the panitumumab + bev/Iri-CT cohort; no significant differences in PFS and OS between cohorts were observed Most patients withdrew due to non-progressive events (59% on panitumumab + bev/Iri-CT arm, 71% on bev/Iri-CT arm), similar to the Ox-CT cohort, limiting the utility of PFS as a valid endpoint in this study Increased response rates with panitumumab + bev/Iri-CT were seen only in wild-type KRAS patients; these findings are consistent with previously reported data on KRAS analyses in the monotherapy setting1-3 Further data collection and analyses are ongoing 1Amado RG et al. JCO 2008, Manuscript in press 2Khambata-Ford S et al. JCO 2007; 25: 3230-3237 3Lievre A et al. Cancer Res 2006;66: 3992-3995

SUMMARY (cont.) Phase 3 registrational studies are currently ongoing to investigate panitumumab with chemotherapy alone in first- line and second-line mCRC Study 20050181 investigates FOLFIRI +/- panitumumab in second-line mCRC (Peeters et al., Abstract #335, Poster #A56) PRIME/Study 20050203 investigates FOLFOX +/- panitumumab in first-line mCRC (Douillard et al., Abstract #443, Poster #A63) Independent data monitoring committees for these studies have recommended continuation per protocol

ACKNOWLEDGEMENTS Patients who participated in this study and their families All investigators, co-investigators, and study staffs at 194 sites across the US The Amgen study team