Genentech, Inc. Protocol GO27912 Covance Central Laboratory Procedures November 2011 This document contains confidential and proprietary information and is the exclusive property of Covance Central Laboratory Services Inc. The reproduction, distribution, modification, performance or other use of this document, or any of the information contained herein, in whole or in part, without the express written consent of Covance Central Laboratory Services Inc, is prohibited. 1

Presentation Training Objectives Ensure you understand the steps needed to ensure subject safety and increase the likelihood of having evaluable subjects at the end of the study Ensure your site has the collection kits and supplies needed throughout the study Use the collection kits according to protocol and visit schedule Ensure properly completed requisition forms so that specimens can be processed without delay Collect samples according to protocol requirements and accepted medical practices Optimize subject safety by minimizing test cancellations or missed visits Pack and ship specimens according to the procedures associated with your region and the needs of your study Contact Covance to order additional supplies or learn the answers to questions you might have

Central Laboratory Topics This presentation provides specific details about: Supplies provided by Covance CLS Collection kit use and inventory management Requisition completion Specimen collection and packaging Courier arrangements Contacting Covance CLS

Covance Central Laboratory Services Location Est. Indianapolis, Indiana, USA 1986 Geneva, Switzerland 1992 Singapore 2000 Shanghai, China 2007 Kawagoe City, Japan 2010 Devoted exclusively to clinical trials Combinable data Global capabilities 4

Supplies Provided By Covance CLS

First Covance CLS Communication Confirm site contact information Correct mistakes and enter any missing information Fax completed form to Covance CLS within 48 hours Ensures: Study supplies shipped to appropriate location E-mail addresses used only for study related issues e.g., reminders of upcoming holidays

Visit-specific collection kits Initial Supplies (1/4) Visit-specific collection kits To obtain the highest quality specimens possible, store collection supplies at the recommended +4°C to 25°C (+39°F to 77°F) Expired kits or kits/supplies in excess at end of study must be destroyed at site, do not return to Covance CLS Visit Screen, CTC/CAP, Arm C/D Urine DNA C1D1, C1D8 Unscheduled # Kits 3 kits each 2 kits each 1 kit 7

Initial Supplies (2/4) Shipping supplies Shipping boxes Ambient and frozen for shipments to Covance Insulated ambient for shipments to Genentech CTC samples Site specific shipping documents Air waybills, UPS shipping labels, Commercial Invoices, return address labels Supplied in envelopes designated by shipping condition 8

Initial Supplies (3/4) Quick Reference Guide Generic Provided in most local languages Kit information tips Requisition completion tips Resupply Inventory control tips 9

Initial Supplies (4/4) Covance CLS Investigator Manual Provided in English Protocol-specific: Laboratory Visit Test Schedule Mock laboratory requisitions Specimen collection and processing information Packaging and shipping instructions Laboratory certifications Renewals to be found at www.covance.com Holiday Observances Covance CLS contact information Courier contact information Section to file Covance CLS communications Review manual prior to first subject visit

Collection Kit Use and Inventory Management

Review for expired kits in preparation of visits Kit Inventory Review Kits are automatically resupplied, except: Lost, damaged or expired kits Check inventory carefully and request replacement kits Allow enough delivery time before scheduling subjects Inform Covance CLS of lost, damaged or expired kits to ensure automatic resupply functions properly Review for expired kits in preparation of visits Expiration Date

Automatic Kit Resupply Contact Covance CLS to adjust / stop automatic resupply

Covance CLS Resupply Requests Request the following supplies from Covance CLS: Replacement of damaged, lost or expired kits Shipping supplies Secure website Confirmatory e-mail sent providing the work order reference number Allow a minimum of 7 working days for the delivery of your resupply order Order supplies online: www.covance.com/kitordering

Interchanging kits or kit components can lead to test cancellations Accession Number A unique identifier assigned to each kit (example: R593812) Protocol, site number and visit name are encoded Located on: Kit box Requisition Each tube and vial 1 Accession Number per kit Reference this number with queries to Covance CLS Do not interchange kits between sites or protocols Do not interchange tubes between kits Interchanging kits or kit components can lead to test cancellations

Collection Kit Content (1/2) Contents are specific to visit on kit label Requisitions Collection tubes and transport vials Pre-labeled with test names Needles and holders Packaging materials Incorrect or missing subject identifier could cause cancellation of testing To label replacement tubes and vials Discard if not needed Write the test name and subject identifier on label SM8 Serum CAP 1234 Write subject’s identifier on labels when drawing specimens 2 extra bar coded labels SM8 Serum CAP 1234

Collection Kit Content (2/2) CTC/CAP and Day 1 Kits Include one of each of the following for CTC samples: 10 mL CellSave Preservative Tube Green bar printed on label 21-gauge butterfly needle Specimen Collection Bag Samples collected with these kits are shipped to Covance CLS and Genentech Specimen details provided on slides 31-33 of this presentation

Requisition Completion

Laboratory Requisition (1/2) Completion is mandatory for sample processing Provided in English Use a black ballpoint pen Draw single line through incorrect information Date and initial correction Includes: Subject demographic section, special instruction(s), administrative question(s) Optional testing: check box to order testing Collection instructions and shipping condition when not enough space on 1st page

Laboratory Requisition (2/2) NCR Copies 3-Part NCR (CTC/CAP and Unscheduled): Ship white copies to Covance CLS Ship pink copies to Genentech with CTC/CAP Retain yellow copies for your records 2-Part NCR (all other visits): Retain pink copies for your records

Laboratory Requisition Completion (1/2) Completion of demographics is mandatory for sample processing Clear + Consistent + Complete = Query Free Requisitions To identify subject G E N E R I C To calculate specimen stability To assist in site communication

Laboratory Requisition Completion (2/2) Provide information using check boxes or written entries CTC/CAP and Arm C/D Urine DNA requisitions Is patient on or off study treatment? C1D1, C1D8, C6D1/C3XD1 and Unscheduled requisitions Provide PK collection date and time DD/MMM/YYYY and 24 hour clock Optional Testing Mark appropriate check box to identify testing to be performed Incomplete information triggers queries

Use of Unscheduled Kits C6D1/C3XD1 This kit is used to draw the GDC-0941 PK samples for patients at C6D1 or crossover patients at crossover Cycle 3 Arm C/D Urine DNA This kit is used to draw the Urine Tumor DNA for Arm C and D patients for all visits after Screen where the Urine Tumor DNA is collected This includes regular visits and crossover visits CTC/CAP This kit is used to draw the CTC and plasma and serum CAP samples every six weeks starting at C1D1 Unscheduled This kit is used to draw unscheduled samples that have been approved by the CRO

C1D1 Visit Pharmacogenetic, CTC/CAP and Urine DNA samples must be drawn pre-dose In addition to collecting C1D1 kit, also collect CTC/CAP kit for all patients Urine DNA kit for all Arm C/D patients The Pharmacogenetic sample is required for all patients unless the local regulatory agency prohibits drawing the Pharmacogenetic sample

Specimen Collection and Packaging

Specimen Types Returned to Covance CLS Frozen Serum √ Plasma Whole Blood Urine Visit test schedule (table of tests per visit) provided in: Study Protocol Covance CLS Investigator Manual Detailed collection and handling instructions provided in: On requisitions within kits

Specimen Management (SM) Testing not performed and not reported by Covance CLS Upon sample receipt Covance CLS will: Register samples in Covance CLS tracking system Verify subject’s ID and sample condition Store samples at appropriate temperature Forward samples to specified laboratory for analysis on schedule directed by Genentech

Collection Key Points (1/3) Good Quality Data Begins With Good Quality Samples Select proper collection tube(s) Thoroughly mix blood by inverting tube Do not draw whole blood samples first Avoids potential tissue thromboplastin contamination and clotting Serum Allow blood to clot upright for 30 minutes Urine Provide adequate sample volume; cap tightly

Collection Key Points (2/3) Centrifugation Room temperature: Serum CAP +2 to 8°C: Plasma samples Tubes may be centrifuged under ambient condition (room temperature) if a refrigerated centrifuge is not available Proper speed and time Refer to Covance CLS Investigator Manual for specific settings May vary from sample to sample Example: minimum of 1500 x g for 15 minutes Clot and serum must be well separated Cells and plasma must be well separated Do not centrifuge when testing requires whole blood or urine samples Use pipette provided in kit to transfer serum/plasma into proper pre-labeled aliquots Plasma: Avoid the red cell layer Specimen transfer

Collection Key Points (3/3) Storage and shipping condition Frozen -70°C If -70°C not available, samples may be stored at -20°C for up to one week Day of collection Back up samples shipped within 1 week Place the collection tube in an ice/water bath and maintain chilled until centrifugation Centrifuge within 60 minutes of collection Transfer plasma into PRIMARY and BACKUP vials Shipping frequency Special PK processing/ instructions

Samples Not Returned to Covance CLS (1/2) Specimen Type Ambient Whole Blood CTC Avoid backflow from CellSave tube during collection Place the patient’s arm in a downward position Hold the tube with the stopper upmost Make sure the solution inside the tube does not touch the stopper or end of the needle during venipuncture Mix tube immediately to prevent clotting Inadequate or delayed mixing may result in inaccurate test results 31

Samples Not Returned to Covance CLS (2/2) Specimen Type Ambient Whole Blood CTC Return CTC samples ambient to Genentech with pink copy of the requisition Use the shipping supplies provided by Covance CLS Ship Monday through Wednesday to: Genentech Sample Management 550 Grandview Drive BLDG 47, Room 1230 (471230) South San Francisco, CA 94080 650-225-2034 Email: 2027912-ctc-d@gene.com Do not return samples to Covance CLS

CTC Packaging Key Points CTC Shipments to Genentech Follow details provided in Covance CLS Manual Required materials provided within the shipping box or in Covance kit BM01DA Shipping Box BM08WFA Foam Liner BM08AV440964 Bubble Mailer BM08GEL Gel Pack The BM08GEL Gel Pack needs to rest in ambient conditions for 72 hours prior to pack-out Pressure Bag (provided in Covance kit) Absorbent (provided in Covance kit)

Packaging Key Points (1/4) Insert tubes into Specimen Collection Bag One Accession Number: Per Specimen Collection Bag Per shipping temperature Include white copy of requisition in outside pouch (make bar code visible) with ambient samples

Packaging Key Points (2/4) Ambient samples Prepare Gel Pak (thermal insulator) to insulate ambient samples Take Gel Pak from kit Fill to indicated line with ambient water Let gel form or massage absorbent pack until gel forms Evenly distribute gel in bag while expelling air Seal tightly Wrap Gel Pak around Specimen Collection Bag containing ambient samples Do not place specimens directly into gel

Packaging Key Points (3/4) Frozen samples Place Specimen Collection Bag in Styrofoam container Group shipments as much as possible Use recommended amount of dry ice Completely surround samples with dry ice

Packaging Key Points (4/4) If a combination box being used Ambient + Frozen Place ambient samples in dedicated section of shipping box Replace lid and close box securely Place site’s address label on shipping box Pre-printed with site’s address and provided by Covance CLS Attach shipping documents to outside of box Keep a copy at the site All shipping conditions

Sample Processing Delays Reasons for processing delays Missing, incomplete or inconsistent data on requisitions Incorrect subject identifiers on returned containers More than one subject per Accession Number Incorrect visit kit used Incorrect sample condition Covance CLS will query the site Samples will not be shipped to referral lab until all queries are resolved Sample processing will be performed upon receipt of the samples 38

Courier Arrangements

Courier Information To Covance To Genentech Canada US Ambient N/A Fed Ex Frozen UPS Dry Ice Provider Site Courier contact information is communicated to the sites in Covance CLS Investigator Manual US only: United Parcel Service (UPS) Saturday morning pickups Confirm Saturday availability/pickup time with UPS Delivered to Covance CLS on Sunday US and Canada: Locate dry ice supplies (site’s responsibility) IATA certification may be required for dry ice shipments per country regulations Consolidate shipments when possible Time and cost effective

Shipping Documents (Canada) Air waybills and Commercial Invoices Commercial Invoice Provided pre-printed by Covance CLS Complete required information Send/attach to appropriate shipping box Ensure Commercial Invoice is included to avoid delivery delays If shipping on Friday, check “Saturday Delivery” on air waybill

UPS Shipping Labels (US) Provided pre-printed by Covance CLS Dedicated to Covance CLS shipments Use dedicated UPS phone number (866-961-3790) to schedule pickup Attach to appropriate shipping box Courier details in Covance CLS Investigator Manual Ensures Friday shipments to be delivered on Saturday

Pickup Information Prior to first shipment to Covance CLS, contact your courier to determine/confirm: Last Call Time, latest time to schedule same day pickup Last Pickup Time, latest time for courier pickup Transit Time to Covance CLS Provide exact pickup location Transit Time to Covance CLS: 24 hours sites: Ship Monday through Friday 48 hours sites: Ship Monday through Thursday Consider customs/local holidays before shipping Refer to Covance Central Laboratory Investigator Manual or http://www.covance.com/products/clinical/central-lab/global-logistics.php Do not ship one day before holidays (2 days if inbound transit is 48 hours) If sample pickup is missed, FROZEN samples remain at instructed temperature Contact Covance CLS Investigator Support Services if you need further advice

Contacting Covance CLS

Who to Contact Contact Covance CLS Contact courier To add/change information at investigator’s site Contact telephone and fax numbers Covance’s CLS supplies delivery address Sample pickup address Query resolution Resupply Place orders Adjust automatic resupply Stop automatic resupply when enrolment is complete Courier issues To order pickup To track packages Contact courier

Primary Reference Material Refer to Covance CLS Manual Covance CLS contact information Toll Free and Direct Numbers telephone numbers If Toll Free unavailable, call telephone operator for collect call to Covance CLS Courier contact information Sample collection instructions Packaging instructions

THANK YOU !