Synta Pharmaceuticals 9090-08 Virginia Castillo

Agenda BARC Project Team Central laboratory services Central laboratory approach Material flow chart Trial-specific material Sample handling Shipping of samples Data integrity Reporting

BARC Project team Virginia Castillo Project Manager 516 719 1040 vcastillo@barcusa.com Jennifer Camejo Project Manager 516 719 1052 jcamejo@barcusa.com

Central lab services Investigator/Monitor information (manual & leaflets) Supplies (sampling & shipping materials) Sample shipment Sample analysis Sample storage Data management Customized reporting Technical support

Central lab approach Ambient shipment to BARC Frozen shipment to BARC LDH LDH isoforms Archived tissue/blocks Frozen shipment to BARC PK Pharmacogenetics (PG) Biomarkers

Study flow chart TESTS TO BE PERFORMED AT BARC X Laboratory tests: Screening Treatment Period Within 4 Weeks of randomiza -tion Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle _ Day 1 (± 3 days) Day 15 (± 3 days) TESTS TO BE PERFORMED AT BARC LDH X LDH isoforms TESTS TO BE PERFORMED BY THIRD PARTY LAB PK sampling Pharmacogenet -ics (PG) sampling Biomarkers Archived Tissue

TESTS TO BE PERFORMED BY THIRD PARTY LAB Study flow chart – PK sampling Tests Treatment Period Cycle 1 Cycle 2 Day 1 (± 3 days) prior to ganetespib infusion termination(EOI)* prior to docetaxel infusion termination (EOI)* prior to ganetespib infusion termination (EOI)* prior to docetaxel infusion termination (EOI)* TESTS TO BE PERFORMED BY THIRD PARTY LAB PK Sampling: Arm A (Docetaxel only): X PK Sampling: Arm B (Ganetespib + Docetaxel): * EOI = End of Infusion

SAMPLES TO BE SHIPPED AMBIENT TO BARC 1 Material needed: Tests Scr Treatment Period Within 4 Weeks of randomiza tion Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle _ Day 1 (± 3 days) Day 15 (± 3 days) Day 1 (± 3 days) Day 1 (± 3 days) Day 1 (± 3 days) SAMPLES TO BE SHIPPED AMBIENT TO BARC SST tube 8.5 mL (marble/brown stopper)* LDH, LDH Isoforms 1 Large brown cap cryovial 5 mL LDH Clear cap cryovial 5 mL Red cap cryovial 5 mL (back-up) LDH/LDH Isoforms Paraffin blocks (histocassette) and/or a minimum of 10 Slides. Archived Tissue SAMPLES TO BE SHIPPED FROZEN TO BARC Sodium Heparin tube 6 mL (green stopper)** PK sampling 1 or 2 Blue cap cryovial 2 mL (Aliquot A) 1 or 2x2 Red cap cryovial 2 mL (Aliquot B) K2EDTA tube 6 mL (violet stopper) PG sampling Biomarkers Orange cap cryovial 2 mL (Aliquot A)- from Sodium Heparin tube 6 mL Violet cap cryovial 2 mL (Aliquot B)- K2EDTA tube 6 mL (violet stopper)** Green cap cryovial 2 mL (Aliquot A)- from K2EDTA tube 6 mL Clear cap cryovial 2 mL (Aliquot B)-

Trial specific material – STUDY DOCUMENTS Central lab Manual Use of Requisition Form- label sheet Description of tests to be carried out Supplies provided and procedure to re-order supplies through Sample Material Request Form (SMRF) + semi automatic resupply (order proposal every 6 months) Sampling procedures and sample management Transport of samples to central lab (courier contact) Analysis and reporting Lab accreditation certificate & reference ranges

Trial specific material – STUDY DOCUMENTS Instruction Leaflet In local language Summary of procedures with comprehensive pictograms (per visit)

Trial specific material – STUDY DOCUMENTS REQUISITION FORM Collection of subject demographic and visit data Identification of various samples drawn ‘Error-proof’: all labels must be used to complete visit Use one form per subject and per visit day Apply barcode labels length wise Every requisition form has a unique requisition # Send original requisition form along with the samples to BARC.

To be completed per subject Trial specific material – STUDY DOCUMENTS Sample log form Log of all samples taken per patient To be completed per subject Labels with unique requisition number should come here (=link between subject and requisition number used) SHOULD BE KEPT ON SITE!

Trial specific material – STUDY DOCUMENTS sample material request form Fill out SMRF and fax to BARC @ 516-719-1281 or email to orders@barcusa.com Re-supply shipping Procedure Re-supply shipments will be shipped within 5 business days after receipt of the order.

Trial specific material – STUDY DOCUMENTS EXAMPLE

Trial specific material – supplies Visit specific kits Local handling Pipettes and transfer vials Shipment and storage material Pre-printed AWB, silver blue box Ambient white Gel packs (do not freeze or referigerate) Storage boxes (grid) All IATA compliant EXCLUSIVELY use BARC SUPPLIES

Trial specific material – supplies Initial supplies Continuation supplies Use Sampling Material Request Form or email at: 9090-08@barcusa.com and orders@barcusa.com

Sample Handling - Ambient LDH and LDH ISOFORMS Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. The SST tube need to site in an upright position for 30 minutes after inversion and before centrifugation.

Sample Handling - Ambient Tumor tissue slides

Sample Handling - Frozen Pharmacogenetics (PG) sampling Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. No further processing required.

Sample Handling - Frozen PK sampling ARM A (Docetaxel) Cycle 1/DAY 1/EOI and Cycle 2/DAY 1/EOI Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. Centrifuge within 1 hour of sampling.

PK sampling ARM B (Ganetespib + Docetaxel) Sample Handling - Frozen PK sampling ARM B (Ganetespib + Docetaxel) Cycle 1/DAY 1/EOI and Cycle 2/DAY 1/EOI Immediately after obtaining the blood specimen, invert the tube 8 to 10 times. Centrifuge within 1 hour of sampling.

Sample Handling - Frozen Biomarker sampling Immediately after obtaining the blood specimens, invert the tubes 8 to 10 times. Centrifuge within 1 hour of sampling.

Shipping of samples - general Subject is best seen in the morning to ensure timely pick-up of the samples Call local courier at telephone number provided by BARC within call hours (info sticker present on manual + leaflet) Make sure all samples in all boxes are properly labeled and original requisition form is added to box

Shipping of samples -general Courier is prepaid by BARC (BARC account number on Air Waybill) Ambient shipments (day of collection) Monday through Friday Frozen shipments (monthly dry ice shipments) Monday through Wednesday Shipments cannot be made on the day before Local Public Holidays or on Local Public Holidays.

Shipment of Samples – Ambient shipment

Shipment of Samples – Frozen shipment

Shipment of Samples – Combined shipment

Data Integrity In order to comply with GCP, any omission or inconsistency will be queried with a Data Clarification Form The DCF must be resolved promptly and returned by fax to BARC

Reporting Fax/Email reports with LDH results to site within 24 hrs after reception Cumulative reporting (up to two visits) Missing results are coded: ‘N D’ « Not done » or ‘N R’ « Not received »

Reporting Out of range values will be flagged with asterix (*) and evaluation box which needs scoring by investigator (CS/NCS)

xx/xx/xxxx Editor: Presentation name here