Targeted Agent and Profiling Utilization Registry (TAPUR ) Study. February 2018

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1 Targeted Agent and Profiling Utilization Registry (TAPUR ) Study February 2018

2 Precision Medicine Therapies designed to target the molecular alteration that aids cancer development 30 TARGET gene alterations (%) Patients with TARGET Gene events by category (%) All Common (5% or greater) Intermediate (2 5%) Rare (Less than 2%) New TARGET Gene Trials TP53 BRAF PIK3CA CDKN2A KRAS NF1 EPHA3 ERBB4 ATM CREBBP EGFR EPHA5 PTEN ROS1 NOTCH2 SMARCA4 APC KDR MLL BRCA2 NOTCH1 NRAS PDGFRA ATR DDR2 EZH2 FLT3 NTRK3 RB1 RET CDH1 FBXW7 PIK3R1 ASXL1 BCL2 CTNNB1 ERBB2 JAK2 MET MTOR STK11 CDKN1B GNAS MAP2K1 SMAD4 SYK ABL1 BRCA1 ERBB3 MYC PTCH1 RUNX1 ALK BRD4 CDK4 ERG FGFR2 IGF1R MSH2 MSH6 NFKBIA AKT1 ETV6 PDGFRB SMO TSC2 WT1 XPO1 AR FGFR1 KIT MDM4 MEN1 CDKN2B CRKL MAP2K4 MDM2 SMAD2 TET2 BAP1 CCND1 CCND2 DNMT3A ESR1 ETV1 EWSR1 FGFR3 GNAQ HRAS IDH1 JAK3 MLH1 RAF1 RARA AURKA BRD3 CCND3 CCNE1 IDH2 MAP2K2 MITF NF2 TMPRSS2 TSC1 VHL BRD2 ETV4 ETV5 MPL SMARCB1 ARAF GNA11 MCL1 NKX2 1 AKT2 AKT3 CDK6 CDKN1A CEBPA A large proportion of cancers may contain at least one plausibly actionable genetic alteration The long tail means that the conventional clinical trial design approach may not be feasible Van Allen, Wagle et al., Nature Med 20, (2014)

3 Problems Patient with advanced cancer; no standard treatment options Genomic profile test performed Potentially actionable aberration detected FDA-approved drug available for aberration How to get the drug that might be beneficial? How to learn from the treatment?

4 Overall Goals of TAPUR To learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target, or to predict sensitivity to a drug To educate oncologists about implementation of precision medicine in clinical practice

5 Who Benefits? Patients receive targeted agent matched to molecular profile broader eligibility criteria Physicians receive interpretation of molecular test results, guidance in treatment recommendations, access to drugs, clinical data on off-label use Industry receives data on drug use and outcomes to inform R&D plans and life cycle management Oncology Community receives data on extent and outcomes of off label drug and test use and real world safety data

6 Eligibility Patients with advanced solid tumors, multiple myeloma or B cell non-hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function

7 TAPUR Study Primary Objective To describe the anti-tumor activity and toxicity of commercially available, targeted anti-cancer drugs prescribed for treatment of patients whose tumors have a genomic variant known to be a drug target, or to predict sensitivity to a drug

8 Study Endpoints and Analysis Primary endpoint: ORR or SD at 16 weeks per relevant response criteria Other endpoints: PFS, OS, time on treatment, grade 3-5 AEs per CTCAE, SAEs Each tumor type-variant-drug is a group Enroll 10 patients/group. If 1 or fewer responses, stop If at least 2 responses, enroll additional 18 7 or more responses/28, further study

9 How does TAPUR work?

10 Participating Pharmaceutical Companies Seven companies currently committed to participate Providing free drug (ongoing access for responders) Per-case payment for over 1200 TAPUR participants Infrastructure support for ASCO staff and study administration

11 Supporting Vendors Syapse Precision Medicine software Electronic data collection platform and study workflows Cardinal Health Specialty Pharmacy Central drug distribution

12 Key Milestones FDA reviewed and determined TAPUR Study IND-exempt (August 2015) Registered on ClincialTrials.gov (February 2016) TAPUR Study Launch (March 2016) Addition of new study therapy; lowered enrollment age to 12 years of age (May 2017) Opened collaborations with international research groups and molecular testing companies (June 2017) Over 100 clinical site locations enrolling participants (December 2017) 600 th participant enrolled (on study drug treatment) (January 2018)

13 For more information: ClinicalTrials.Gov: NCT#