Central Laboratory Sample and Results Sharing JACOB (BO25114) and MetGastric (YO28322)

What is JACOB and MetGastric? JACOB is a pertuzumab, first-line, HER2-Positive phase III trial in patients with Gastroesophageal Cancer MetGastric is an onartuzumab, first-line, HER2-Negative, Met-Positive phase III trial in patients with Gastroesophageal Cancer Similar inclusion and exclusion criteria: ECOG performance status of 0 or 1 Life expectancy > 3 months Measurable disease or non-measurable but evaluable disease, according to RECIST v1.1

Rationale for Sharing Samples One sample/test = option to participate in two studies Utilize 61 overlapping JACOB and MetGastric sites across the globe (4 in Canada and 7 in US) Same methodology for HER2 tests including IHC and ddISH Results can be transferred from MetGastric to JACOB and vice versa* * Recommendation is to screen patient onto MetGastric first

Countries with Overlapping Sites Approximately 61 sites are overlapping between JACOB and MetGastric Europe Overlap Sites Belgium 1 Czech Republic France 4 Germany 3 Italy 5 Turkey 2 Poland Russia Switzerland Spain Total 29 Asia Pacific Overlap Sites Australia 3 South Korea 5 Malaysia 2 Taiwan Thailand Total 17 Americas Overlap Sites Brazil 2 Canada 4 Mexico 1 Panama USA 7 Total 15

Overlapping Sites in North America 11 sites are overlapping between JACOB and MetGastric Country Site Name YO28322 (MetGastric) BO25114 (JACOB) Site # PI Canada Sunnybrook Odette Cancer Centre 247145 Berry 249107 Mount Sinai Hospital; Oncology 247143 Burkes 249109 Hamilton Health Sciences - General Site 247426 Dhesy-Thind 249106 McGill University; Sir Mortimer B Davis Jewish General Hospital 248274 Kavan 253861 Alcindor

Overlapping Sites in North America 11 sites are overlapping between JACOB and MetGastric Country Site Name YO28322 (MetGastric) BO25114 (JACOB) Site # PI USA University Of Chicago Medical Center 247946 Catenacci 256217 Texas Oncology 258228 Richards 255820 Rocky Mountain Cancer Centers 258223 Cohn 255816 New York Oncology Hematology 247898 Garbo 255818 Demarco Tennessee Oncology 248156 Bendell 260737 Florida Cancer Specialists, North 258221 Acs 261055 Florida Cancer Specialists, Fort Myers 258227 Reeves 261056

Sample Sharing Scenarios Scenario 1 Patient screened onto MetGastric first* Scenario 2 Patient screened onto JACOB first * Recommended scenario as no additional samples may be required

Scenario 1 • Recommended Patient screened in MetGastric first ICF signed for MetGastric Screening Call in IXRS for MetGastric Dispatch FFPE tumor block to Targos (or at least 15 slides) HER2 testing performed at Targos Continue with other screening activities until HER2 result from Targos is available via fax HER2- IXRS notification that subject is MET eligible Randomization call for MetGastric in IXRS HER2+ SF Call in IXRS for MetGastric ICF signed for JACOB Screening for JACOB; enter MetGastric screening number as reference Request for Results Transfer form completed by site and fax to Targos* Targos faxes JACOB eligibility results form to acknowledge success transfer in 2 working days Randomization for JACOB in IXRS * If the fixative is not 10% NBF Targos will query sites

Scenario 1 Patient Screened onto MetGastric first Patient signs ICF for MetGastric Site makes screening call in IXRS (Bracket) Site sends tissue block or 15 slides to Targos Site receives HER2 result from Targos via fax If result is HER2 negative, site waits for MET result sent via an email from IXRS. If MET eligible, site makes randomization call in IXRS for MetGastric If result is HER2 positive, site makes screening failure call for MetGastric and proceed screening for JACOB

Scenario 1 Patient Screened onto MetGastric first Site makes screening call for JACOB and enter MetGastric screening number as reference Site completes the Request for Results Transfer form and faxes to Targos Patient signs ICF for JACOB Targos faxes the JACOB HER2 results to site within 2 working days Targos checks if samples fixed with 10% NBF and queries site if necessary

Scenario 1 Patient Screened onto MetGastric first Upon receipt of Eligibility Results Form If results transferred successfully, site makes randomization call in IXRS If results not transferred successfully, site receives a query or notification of why the transfer could not be completed For general enquiries regarding samples and results transfer logistics, site contacts monitors and Targos at bo25114_Targos_contact@targos-gmbh.de

Screening Call in IXRS for JACOB HER2 testing performed at Targos Scenario 2 • Exceptions Patient screened in JACOB first ICF signed for JACOB Screening Call in IXRS for JACOB Dispatch FFPE tumor block to Targos (or at least 15 slides) HER2 testing performed at Targos Continue with other screening activities until HER2 result from Targos is available via fax HER2- SF Call in IXRS for JACOB ICF signed and screening for MetGastric Results Transfer form completed by site and fax to Targos Targos performs Met test and upload to IXRS and faxes MetGastric eligibility results form to site (TAT – 3 working days)* Randomization for MetGastric in IXRS HER2+ Randomization call in IXRS for JACOB * If there is not sufficient material for results transfer, Targos will query site, MET test and results transfer cannot be done; additional slides will need to be provided

Scenario 2 Patient Screened onto JACOB first Patient signs ICF for JACOB Site makes screening call in IXRS (Almac) Site sends tissue block or 15 slides to Targos Site receives HER2 result from Targos via fax If result is HER2 positive, site makes randomization call for JACOB If result is HER2 negative, site makes screening failure call for JACOB and proceed screening for MetGastric

Scenario 2 Patient Screened onto JACOB first Site makes screening call for MetGastric Site completes the Request for Results Transfer form and faxes to Targos Patient signs ICF for MetGastric Targos informs site/monitor if additional slides are needed Targos checks if samples are sufficient for additional MetGastric tests Site sends additional slides, if necessary

Scenario 2 Patient Screened onto JACOB first Targos performs Met test, uploads results to IXRS and Targos faxes HER2 eligibility results form to site in 3 working days Site receives IXRS email for patient Met eligibility If Met eligible, site makes randomization call in IXRS If Met ineligible, site makes screen failure call in IXRS For general enquiries regarding samples and results transfer logistics, site contacts monitors and Targos at yo28322_Targos_contact@targos-gmbh.de

Clinical Trial Monitor Checklist Stress that site should use the correct tissue requisition form Ensure that site is not being paid twice for screening assessments JACOB CTMs should check the screening figures with MetGastric CTMs HER2 screening status documented in remote monitoring report as a subject issue in CTMS system Ensure the site uses 10% NBF to fix blocks (requirement for JACOB) Patient referral from non-overlapping site would need Request for Results Transfer form completed with original screening number and site number to transfer results to the other study Please review all the sample sharing documents on Shareweb and train your sites accordingly

Study Site Checklist Determine if site is participating in both studies Receive acknowledgment from Targos of successful transfer of HER2 results via Eligibility Results form Ensure ICF is signed by subject for the screening study If HER2-Positive Collect tumor blocks or 15 slides for central testing at Targos Screen fail subject in MetGastric IXRS Use the appropriate tissue requisition form Consent subject into JACOB Screen subject in IVRS for JACOB Receive Eligibility Results form for original study on HER2 status If HER2-Negative Screen fail subject in JACOB IXRS Complete the Request for Results Transfer form checking the relevant boxes Consent subject into MetGastric Screen subject in IVRS for MetGastric

MetGastric Tissue Requisition Form

JACOB Tissue Requisition Form

Request for Results Transfer Form Referral from non-overlapping site would need to complete this with original screening number and site number for results transfer

MetGastric Eligibility Result Form

JACOB Eligibility Result Form