MetGastric Study (YO28322)&

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

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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

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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

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Europe Overlap SitesBelgium 1

Czech Republic 1France 4

Germany 3Italy 5

Turkey 2Poland 4Russia 4

Switzerland 2Spain 3

Total 29

Countries with Overlapping SitesApproximately 61 sites are overlapping between JACOB and MetGastric

Asia Pacific Overlap SitesAustralia 3

South Korea 5Malaysia 2Taiwan 2

Thailand 5

Total 17

Americas Overlap SitesBrazil 2

Canada 4Mexico 1Panama 1

USA 7

Total 15

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Overlapping Sites in North America 11 sites are overlapping between JACOB and MetGastric

Country Site NameYO28322

(MetGastric)BO25114(JACOB)

Site # PI Site # PI

Canada

Sunnybrook Odette Cancer Centre 247145 Berry 249107 Berry

Mount Sinai Hospital; Oncology 247143 Burkes 249109 Burkes

Hamilton Health Sciences - General Site 247426 Dhesy-Thind 249106 Dhesy-Thind

McGill University; Sir Mortimer B Davis Jewish General Hospital 248274 Kavan 253861 Alcindor

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Overlapping Sites in North America11 sites are overlapping between JACOB and MetGastric

Country Site NameYO28322

(MetGastric)BO25114(JACOB)

Site # PI Site # PI

USA

University Of Chicago Medical Center 247946 Catenacci 256217 Catenacci

Texas Oncology 258228 Richards 255820 Richards

Rocky Mountain Cancer Centers 258223 Cohn 255816 Cohn

New York Oncology Hematology 247898 Garbo 255818 Demarco

Tennessee Oncology 248156 Bendell 260737 Bendell

Florida Cancer Specialists, North 258221 Acs 261055 Acs

Florida Cancer Specialists, Fort Myers 258227 Reeves 261056 Reeves

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Sample Sharing Scenarios

* Recommended scenario as no additional samples may be required

Scenario 1Patient screened ontoMetGastric first*

Scenario 2Patient screened ontoJACOB first

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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 TargosContinue 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

Scenario 1 • RecommendedPatient screened in MetGastric first

*If the fixative is not 10% NBF Targos will query sites

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Scenario 1Patient 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

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Scenario 1Patient Screened onto MetGastric first

Patient signs ICF for JACOB

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

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

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Scenario 1Patient 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

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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 TargosContinue 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

Scenario 2 • ExceptionsPatient screened in JACOB first

*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

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Scenario 2Patient 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

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Scenario 2Patient Screened onto JACOB first

Patient signs ICF for MetGastric

Site completes the Request for Results Transfer form and

faxes to Targos

Site makes screening call for

MetGastric

Targos checks if samples are sufficient

for additional MetGastric tests

Site sends additional slides,

if necessary

Targos informs site/monitor if

additional slides are needed

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Scenario 2Patient 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

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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

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Study Site Checklist

• Determine if site is participating in both studies

• Ensure ICF is signed by subject for the screening study

• Collect tumor blocks or 15 slides for central testing at Targos

• Use the appropriate tissue requisition form

• Receive Eligibility Results form for original study on HER2 status

• Complete the Request for Results Transfer form checking the relevant boxes

• Receive acknowledgment from Targos of successful transfer of HER2 results via Eligibility Results form

• If HER2-Positive• Screen fail subject in MetGastric

IXRS• Consent subject into JACOB• Screen subject in IVRS for JACOB

• If HER2-Negative• Screen fail subject in JACOB IXRS• Consent subject into MetGastric• Screen subject in IVRS for

MetGastric

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MetGastric Tissue Requisition Form

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JACOB Tissue Requisition Form

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

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MetGastric Eligibility Result Form

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JACOB Eligibility Result Form

MetGastric Study (YO28322)&