BASED ON PROTOCOL VERSION 1 SEPTEMBER 2012 A new study evaluating an investigational drug to treat patients with HER2-positive metastatic gastroesophageal junction and gastric cancer. Study Referral Brochure

Rationale Advanced adenocarcinoma of stomach or GEJ remains lethal disease with low 5-year survival rate, with median OS < 1 year Chemotherapy with fluoropyrimidines and platinum-based agents (FP) constitutes backbone of combination regimens Now recognized that roughly 20% of adenocarcinomas of stomach or GEJ overexpress HER2 Clinical benefit of adding anti-HER2 therapy (trastuzumab) to FP (TFP) chemotherapy demonstrated in ToGA study and now established worldwide as treatment option for patients with HER2-positive metastatic GEJ/GC Pertuzumab augments antitumor effects of trastuzumab against HER2-positive tumors, with or without chemotherapy JACOB study is being conducted to determine whether addition of pertuzumab to standard regimen of TFP chemotherapy in HER2-positive AGC improves OS with acceptable safety profile Sponsor: F. Hoffmann-La Roche Ltd. Study Status Phase III, Randomized, Double Blind, Placebo Controlled Currently recruiting ~780 patients required (~38 months recruitment) Study End = Final OS analysis (n = 502 events) AND 5 years cardiac safety follow-up for last patient who received study treatment Study Name and Number: JACOB Study BO25114

Primary To compare OS in patients treated with pertuzumab in addition to TFP versus patients treated with placebo in addition to TFP JACOB Study Objectives Secondary To compare investigator-assessed PFS, ORR, duration of objective response (DoR), and clinical benefit rate (CBR) between the two treatment arms To compare the safety profile between the two treatment arms To assess the pharmacokinetics of pertuzumab To compare the patient-reported outcomes (PROs) of health-related quality of life (HRQoL) for patients in each treatment arm

The JACOB Study (BO25114) Design Randomization (1:1) n = 780 (approximately 390 per treatment arm) Follow-Up # Study Treatment ~ 6 treatment cycles (21 day cycle) Study Treatment HER2 targeted therapy continues until PD or unacceptable toxicity HER2-positive Metastatic gastric/GEJ adenocarcinoma IHC 3+ or IHC 2+/ISH+ (central testing required) ECOG PS 0 or 1 Key Eligibility Criteria: *After Cycle 6, continuation of chemotherapy is at physician’s discretion Primary Endpoint OS (Events = 502) Secondary Endpoints PFS, ORR, DoR, CBR, Safety, PK, QOL Treatment Arm A Treatment Arm B Capecitabine or 5FU + Cisplatin Trastuzumab + Pertuzumab 840 mg IV Q3W Trastuzumab + Pertuzumab placebo IV Q3W * * # If patients permanently stop study treatment (HER2-directed), they continue to be followed for side effects and cardiac monitoring

JACOB Study Population 780 patients will be enrolled from ≅ 200 sites globally over a 38 month period Key Eligibility Criteria Histologically confirmed metastatic adenocarcinoma of stomach or GEJ HER2-positive tumor defined as either IHC 3+ or IHC 2+ (latter in combination with ISH+), centrally assessed on a primary or metastatic tumor Measurable or evaluable non- measurable disease as assessed by the investigator, according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) PS 0 or 1 Life expectancy ≥ 3 months* Key Non-eligibility Criteria Previous chemotherapy for advanced (metastatic) disease History of exposure to maximum cumulative doses of anthracyclines Evidence of disease progression within 6 months after completion of neoadjuvant or adjuvant chemo- or radio-therapy for gastric/GEJ cancer Any previous HER2-directed therapy Radiotherapy within 30 days of 1 st dose of study treatment History or evidence of brain metastasis Significant CV history/condition (e.g. recent MI; LVEF<55%; NYHA CHF; poorly controlled hypertension)* * For more information, please refer and search for NCT

Additional Information Translational Research Translational research will be a part of the clinical trial Patients may also provide optional samples for further biomarker research Public registry of clinical trials trials.com/trialDetailsGet.action?studyNumber=BO25114&pro ductGenericName=pertuzumab+%5BPerjeta%5D&productTyp e=Drug&divisionName=PHA erm=BO25114&rank=1&show_locs=Y#locn

Contact Information If you are interested in learning more about the JACOB study and/or think you have a patient potentially eligible for this study, please contact the physician detailed here. Contact Details Doctor/Nurse Name: Study Center: Address: If interested in this study or require more information