Oncofocus. Patient Test Report

Transcription

1 Oncofocus Patient Test Report

2 Oncofocus Patient Test Report Oncologica UK Ltd, Suite 15-16, The Science Village, Chesterford Research Park, Cambridge, CB10 1XL - Tel: +44 (0) info@oncologica.com SUBJECT INFORMATION : ( ) Date of B irth: (dd/mm/yyyy) Gender: M F SPECIMEN INFORMATION SITE INFORMATION Site ID: Phone: : No.: Date S pecimen R eceived: Date Reported: T TEST RESULTS Mutations In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available Gene Amino Acid Change Genotype Class cation Current FDA Information NCCN Guideline Number of therapies in clinical trials KRAS p.ala146thr c.436g>a Gain of F unction KIT p.met541leu c.1612a>c Gain of F unction MET p.asn375ser c.1124a>g Gain of F unction Copy Number Variations Gene Type Class cation ER Current FDA Information NCCN Guideline Number of therapies in clinical trials Fusion n s Class cation Current FDA Information NCCN Guideline RET Fusion 1 Number of therapies in clinical trials 1 Other mutations, copy number variations, or fusions that were detected but not classifed by the Oncofocus Reporter as a genetic driver of cancer are not listed in the results section of this report. All other genes listed in the Test Description that do not appear in the results section either did not have a detected variant or the variant is not classifed as a genetic driver for cancer.

3 KRAS A146 mutation in Colorectal Cancer 1 of 9 Published therapies summary In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* cetuximab panitumumab panitumumab + chemotherapy (II) regorafenib + FOLFIRI (II) sorafenib + cetuximab (II) binimetinib + panitumumab (I/II) BVD-523 (I/II) navitoclax + trametinib (I/II) palbociclib (I/II) binimetinib + BYL-719 (I) BMS (I) buparlisib + irinotecan (I) cobimetinib + RG-7446 (I) MEHD-7945A + cobimetinib (I) PD PF , PF irinotecan, PD irinotecan (I) trametinib + uprosertib (I) vorinostat + hydroxychloroquine (I) * Most advanced phase is shown and multiple clinical trials may be available. See Open clinical trials section in the pages to follow.

4 KRAS A146 mutation in Colorectal Cancer 2 of 9 Evidence and prevalence summary by class A class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to unique citations (Current FDA information, NCCN Guidelines, or clinical trial eligibility criteria). An estimate of prevalence of the gene variant in the cancer type is provided. Prevalence Class Evidence items This cancer type KRAS mutation status % KRAS mutation % KRAS non-g12 mutation 1 8.1% KRAS A146 mutation 1 <1% Published therapies detail In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines NCCN Guidelines information is current as of For the most up-to-date information, go to cetuximab Cancer type: Colorectal Cancer KRAS mutation Contraindication: Based upon lower-level evidence, there is uniform NCCN consensus (Category 2A) that patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or pantitumumab. (COL-A 4 of 5, MS-34) NCCN Guideline Version Colon Cancer cetuximab Cancer type: Colorectal Cancer KRAS mutation Contraindication: Based upon lower-level evidence, there is uniform NCCN consensus (Category 2A) that patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or pantitumumab. (REC-A 5 of 6, MS-29 and MS-30) NCCN Guideline Version Rectal Cancer

5 KRAS A146 mutation in Colorectal Cancer 3 of 9 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to panitumumab Cancer type: Colorectal Cancer KRAS mutation Contraindication: Based upon lower-level evidence, there is uniform NCCN consensus (Category 2A) that patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or pantitumumab. (COL-A 4 of 5, MS-34) NCCN Guideline Version Colon Cancer panitumumab Cancer type: Colorectal Cancer KRAS mutation Contraindication: Based upon lower-level evidence, there is uniform NCCN consensus (Category 2A) that patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or pantitumumab. (REC-A 5 of 6, MS-29 and MS-30) NCCN Guideline Version Rectal Cancer Open clinical trials Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Randomized Phase II Study of Hepatic Arterial Infusion With Intravenous Irinotecan, 5FU and Leucovorin With or Without Panitumumab, in Patients With Wild Type KRAS Who Have Resected Hepatic Metastases From Colorectal Cancer KRAS non-g12 mutation First line, Liver mets, Second line or greater/refractory/relapsed, Stage IV II panitumumab + chemotherapy NJ, NY Multiple contacts: See for complete list of contacts.

6 KRAS A146 mutation in Colorectal Cancer 4 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : Multi-Center, Randomized, Placebo-Controlled Phase II Study of Regorafenib in Combination With FOLFIRI Versus Placebo With FOLFIRI as Second-Line Therapy in Patients With Metastatic Colorectal Cancer KRAS mutation Second line or greater/refractory/relapsed, Stage IV II regorafenib + FOLFIRI CO, FL, GA, IN, NY, NC, OH, VA, WA Multiple contacts: See for complete list of contacts. NCT : A Phase II Study of BAY (Sorafenib) in Combination With Cetuximab (Erbitux ) in EGFR Expressing Metastatic Colorectal Cancer (CRC) KRAS mutation Second line or greater/refractory/relapsed, Stage IV II sorafenib + cetuximab MD Multiple contacts: See for complete list of contacts. NCT : An Open Label, Two-Part, Phase Ib/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor Trametinib and the BCL2-Family Inhibitor Navitoclax (ABT- 263) in Combination in Subjects With KRAS Mutation-Positive Advanced Solid Tumors KRAS A146 mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I/II navitoclax + trametinib MA Multiple contacts: See for complete list of contacts.

7 KRAS A146 mutation in Colorectal Cancer 5 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer KRAS mutation Second line or greater/refractory/relapsed, Stage IV I/II binimetinib + panitumumab CA Novartis Pharmaceuticals [ ] NCT : Phase I/II Dose- Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523, an ERK 1/2 Inhibitor, in Patients With Advanced Malignancies KRAS mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I/II BVD-523 FL, TN Multiple contacts: See for complete list of contacts. NCT : Phase I/II Study of the CDK4/6 Inhibitor Palbociclib (PD ) in Combination With the MEK Inhibitor PD for Patients With KRAS Mutant Non-Small Cell Lung Cancer and Other Solid Tumors KRAS mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I/II palbociclib MA Multiple contacts: See for complete list of contacts.

8 KRAS A146 mutation in Colorectal Cancer 6 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase Ib Open-label, Multi-center, Dose Escalation and Expansion Study of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors KRAS mutation HER2 negative, High risk, Second line or greater/refractory/relapsed, Stage II, Stage III, Stage IV, Triple receptor negative I binimetinib + BYL-719 CA, IL, MA, TX, UT Novartis Pharmaceuticals [ ] NCT : A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer KRAS mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I buparlisib + irinotecan KS Stacey Purinton [ ;spurinton@kumc.edu]

9 KRAS A146 mutation in Colorectal Cancer 7 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase Ib Study of the Safety and Pharmacology of MPDL3280A Administered with Cobimetinib in Patients with Locally Advanced or Metastatic Solid Tumors KRAS mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I cobimetinib + RG-7446 NY, NC, TN Reference Study ID Number: GP28363 [ ; global.rochegenentechtrials@roche.com] NCT : A Phase Ib, Open-Label, Dose-Escalation Study of The Safety, Tolerability, and Pharmacokinetics Of MEHD7945A and GDC-0973 In Patients with Locally Advanced or Metastatic Solid Tumors with Mutant Kras KRAS mutation Second line or greater/refractory/relapsed, Stage III, Stage IV I MEHD-7945A + cobimetinib CA, CO, MI, TN, TX Reference Study ID Number: GO29030 [ ; global.rochegenentechtrials@roche.com]

10 KRAS A146 mutation in Colorectal Cancer 8 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Multi-Arm Phase I Dose Escalation Study Of The Safety, Pharmacokinetics, And Pharmacodynamics Of The Dual PI3K/mTOR Inhibitors PF And PF In Combination With Experimental Or Approved Anticancer Agents In Patients With Advanced Cancer KRAS mutation Second line or greater/refractory/relapsed, Stage II, Stage III, Stage IV I PD PF , PF irinotecan, PD irinotecan CA, CO, SC Pfizer CT.gov Call Center [ ] NCT : A Phase I Dose Escalation Open-Label Safety, Pharmacokinetic and Pharmacodynamic Study to Determine the Recommended Phase II Dose of GSK Dosed in Combination With GSK KRAS mutation HER2 negative, Recurrent, Second line or greater/refractory/relapsed, Stage III, Stage IV, Triple receptor negative I trametinib + uprosertib CO, MA, NJ, TN, TX, UT US GSK Clinical Trials Call Center [ ; GSKClinicalSupportHD@gsk.com]

11 KRAS A146 mutation in Colorectal Cancer 9 of 9 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS in Subjects With Advanced Solid Tumors KRAS mutation status HER2 negative, Second line or greater/refractory/relapsed, Stage III, Stage IV, Triple receptor negative I BMS CA, MI, MS, TX Multiple contacts: See for complete list of contacts. NCT : Inhibition of Autophagy in Solid Tumors: A Phase I Pharmacokinetic and Pharmacodynamic Study of Hydroxychloroquine in Combination With the HDAC Inhibitor Vorinostat for the Treatment of Patients With Advanced Solid Tumors With an Expansion Study in Advanced Renal and Colorectal Cancer. KRAS mutation status Second line or greater/refractory/relapsed, Stage III, Stage IV I vorinostat + hydroxychloroquine TX Epp Goodwin [ ; onctrial@idd.org]

12 KIT mutation in Colorectal Cancer 1 of 2 Published therapies summary In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* imatinib mesylate imatinib mesylate + ipilimumab (I) * Most advanced phase is shown and multiple clinical trials may be available. See Open clinical trials section in the pages to follow. Evidence and prevalence summary by class A class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to unique citations (Current FDA information, NCCN Guidelines, or clinical trial eligibility criteria). An estimate of prevalence of the gene variant in the cancer type is provided. Prevalence Class Evidence items This cancer type KIT mutation 2 <1%

13 KIT mutation in Colorectal Cancer 2 of 2 Published therapies detail In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines NCCN Guidelines information is current as of For the most up-to-date information, go to imatinib mesylate Cancer type: Melanoma KIT mutation 2A Advanced or metastatic melanoma (Not specified) NCCN Guideline Version Melanoma Open clinical trials Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-kit Inhibitor) in Patients With Advanced Malignancies KIT mutation Metastatic, Second line or greater/refractory/relapsed, Stage III, Stage IV, Unresectable I imatinib mesylate + ipilimumab TX David S. Hong [ ]

14 MET mutation in Colorectal Cancer 1 of 3 Published therapies summary In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* AMG-337 (I) crizotinib + dasatinib (I) crizotinib + pazopanib, crizotinib + pemetrexed, crizotinib + pazopanib + pemetrexed (I) * Most advanced phase is shown and multiple clinical trials may be available. See Open clinical trials section in the pages to follow. Evidence and prevalence summary by class A class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to unique citations (Current FDA information, NCCN Guidelines, or clinical trial eligibility criteria). An estimate of prevalence of the gene variant in the cancer type is provided. Prevalence Class Evidence items This cancer type MET positive 0 <1% MET mutation 3 <1%

15 MET mutation in Colorectal Cancer 2 of 3 Published therapies detail Open clinical trials Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase I, First-In- Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AMG 337 in Adult Subjects With Advanced Solid Tumors MET mutation Hormone refractory, Second line or greater/refractory/relapsed, Stage III, Stage IV I AMG-337 CA, IL, MA, MI, OH, TN, TX Amgen Call Center [ ] NCT : A Phase I Trial of Dasatinib in Combination With Crizotinib in Patients With Advanced Malignancies MET mutation Aggressive, Classical, Indolent, Nodular lymphocyte-predominant, Second line or greater/refractory/relapsed, Stage IV I crizotinib + dasatinib TX Dr. David S. Hong [ ]

16 MET mutation in Colorectal Cancer 3 of 3 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Two Steps Phase I Trial of Pazopanib or Pemetrexed in Combination With Crizotinib Followed by the Triplet, Crizotinib Plus Pazopanib Plus Pemetrexed in Patients With Advanced Malignancies MET mutation Second line or greater/refractory/relapsed, Stage IV I crizotinib + pazopanib, crizotinib + pemetrexed, crizotinib + pazopanib + pemetrexed TX Dr Ralph Zinner [ , ]

17 in Colorectal Cancer 1 of 10 Published therapies summary In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* ado-trastuzumab emtansine pertuzumab + trastuzumab + docetaxel trastuzumab lapatinib + capecitabine lapatinib + trastuzumab pertuzumab + trastuzumab pertuzumab + trastuzumab + chemotherapy pertuzumab + trastuzumab + paclitaxel trastuzumab + capecitabine trastuzumab + chemotherapy trastuzumab + chemotherapy (other) trastuzumab + cisplatin + fluoropyrimidine trastuzumab + docetaxel trastuzumab + paclitaxel trastuzumab + vinorelbine erlotinib, pertuzumab + trastuzumab, vemurafenib, vismodegib (II) MSC A (I) * Most advanced phase is shown and multiple clinical trials may be available. See open clinical trials section in the pages to follow.

18 in Colorectal Cancer 2 of 10 Evidence and prevalence summary by class A class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to unique citations (Current FDA information, NCCN Guidelines, or clinical trial eligibility criteria). An estimate of prevalence of the gene variant in the cancer type is provided. Prevalence Class Evidence items This cancer type ERBB2 aberration 1 1.9% ERBB2 positive 4 2.0% % Published therapies detail In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated Current FDA information FDA drug label information is current as of For the most up-to-date information, search by drug. ado-trastuzumab emtansine Label as of: Indications and usage: KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: Received prior therapy for metastatic disease, or Developed disease recurrence during or within six months of completing adjuvant therapy.

19 in Colorectal Cancer 3 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated Current FDA information (cont'd) FDA drug label information is current as of For the most up-to-date information, search by drug. pertuzumab + trastuzumab + docetaxel Label as of: Indications and usage: PERJETA is a HER2/neu receptor antagonist indicated for: Use in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti- HER2 therapy or chemotherapy for metastatic disease Use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating improvement in event-free survival or overall survival. Limitations of Use: The safety of PERJETA as part of a doxorubicin-containing regimen has not been established. The safety of PERJETA administered for greater than 6 cycles for early breast cancer has not been established. trastuzumab, Gastric Cancer Label as of: Indications and usage: Herceptin is a HER2/neu receptor antagonist indicated for: the treatment of HER2 overexpressing breast cancer the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma

20 in Colorectal Cancer 4 of 10 NCCN Guidelines NCCN Guidelines information is current as of For the most up-to-date information, go to pertuzumab + trastuzumab + docetaxel 1 Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer trastuzumab + chemotherapy 1 Tumors >1cm (Not specified) One or more > 2mm ipsilateral axillary lymph node metastases (Not specified) NCCN Guidelines Version Breast Cancer ado-trastuzumab emtansine 2A Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified) NCCN Guidelines Version Breast Cancer lapatinib + capecitabine 2A Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified) NCCN Guidelines Version Breast Cancer

21 in Colorectal Cancer 5 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to lapatinib + trastuzumab 2A Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified) NCCN Guidelines Version Breast Cancer pertuzumab + trastuzumab 2A Disease progression after treatment with trastuzumab-based therapy without pertuzumab (Not specified) NCCN Guidelines Version Breast Cancer pertuzumab + trastuzumab + chemotherapy 2A Did not receive pertuzumab as part of neoadjuvant therapy (Neoadjuvant/adjuvant therapy) Disease progression after treatment with trastuzumab-based therapy without pertuzumab (Not specified) NCCN Guidelines Version Breast Cancer

22 in Colorectal Cancer 6 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to pertuzumab + trastuzumab + paclitaxel 2A Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer trastuzumab 2A Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer trastuzumab + capecitabine 2A Metastatic breast cancer (First-line therapy) Metastatic breast cancer previously treated with trastuzumab-based regimen (Not specified) NCCN Guidelines Version Breast Cancer

23 in Colorectal Cancer 7 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to trastuzumab + chemotherapy 2A Tumors cm, node-negative (Not specified) Smaller tumors that have < 2mm axillary node metastases (Not specified) Not specified (Neoadjuvant/adjuvant therapy) Metastatic breast cancer (First-line therapy) Metastatic breast cancer previously treated with a trastuzumab-based regimen (Not specified) Inflammatory breast cancer (Not specified) NCCN Guidelines Version Breast Cancer trastuzumab + docetaxel 2A Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer trastuzumab + paclitaxel 2A Low-risk stage I disease, particularly those not eligible for other standard adjuvant regimens due to comorbidities (Neoadjuvant/adjuvant therapy) Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer

24 in Colorectal Cancer 8 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to trastuzumab + vinorelbine 2A Metastatic breast cancer (First-line therapy) NCCN Guidelines Version Breast Cancer trastuzumab + cisplatin + fluoropyrimidine Cancer type: Esophageal Cancer ERBB2 positive 1 Locally advanced or metastatic adenocarcinoma (First-line therapy) NCCN Guidelines Version Esophageal and Esophagogastric Junction Cancers trastuzumab + cisplatin + fluoropyrimidine Cancer type: Gastric Cancer ERBB2 positive 1 Locally advanced or metastatic gastric cancer (First-line therapy) NCCN Guidelines Version Gastric Cancer trastuzumab + chemotherapy (other) Cancer type: Esophageal Cancer ERBB2 positive 2B Locally advanced or metastatic adenocarcinoma (Not specified) NCCN Guidelines Version Esophageal and Esophagogastric Junction Cancers.

25 in Colorectal Cancer 9 of 10 In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines (cont'd) NCCN Guidelines information is current as of For the most up-to-date information, go to trastuzumab + chemotherapy (other) Cancer type: Gastric Cancer ERBB2 positive 2B Locally advanced or metastatic gastric cancer (Not specified) NCCN Guidelines Version Gastric Cancer Open clinical trials Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : My Pathway: An Open Label Phase IIa Study Evaluating Trastuzumab/Pertuzumab, Erlotinib, Vemurafenib, and Vismodegib in Patients Who Have Advanced Solid Tumors With Mutations or Gene Expression Abnormalities Predictive of Response to One of These Agents Second line or greater/refractory/relapsed, Stage IV II erlotinib, pertuzumab + trastuzumab, vemurafenib, vismodegib AR, AZ, CA, CT, FL, GA, IL, MD, ND, OH, OK, PA, SD, TN, TX, VA, WA Reference Study ID Number: ML28897 [ ; global.rochegenentechtrials@roche.com]

26 in Colorectal Cancer 10 of 10 Open clinical trials (cont'd) Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : A Phase I, First-in- Human, Dose Escalation Trial of MSC A, a Dual p70s6k/akt Inhibitor, in Subjects With Advanced Malignancies ERBB2 aberration Aggressive, Classical, EGFR, HER2 positive, Indolent, Nodular lymphocyte-predominant, Second line or greater/refractory/relapsed, Stage III, Stage IV I MSC A CA, MN, TX, VT US Medical Information [ ]

27 RET fusion in Colorectal Cancer 1 of 2 Published therapies summary In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* cabozantinib ponatinib (II) * Most advanced phase is shown and multiple clinical trials may be available. See open clinical trials section in the pages to follow. Evidence and prevalence summary by class A class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to unique citations (Current FDA information, NCCN Guidelines, or clinical trial eligibility criteria). An estimate of prevalence of the gene variant in the cancer type is provided. Prevalence Class Evidence items This cancer type RET aberration 1 <1% RET fusion 1 unknown

28 RET fusion in Colorectal Cancer 2 of 2 Published therapies detail In this cancer type In other cancer types In this cancer type and other cancer types Contraindicated NCCN Guidelines NCCN Guidelines information is current as of For the most up-to-date information, go to cabozantinib Cancer type: Non-Small Cell Lung Cancer RET fusion 2B Not specified (Not specified) NCCN Guidelines Version Non-Small Cell Lung Cancer Open clinical trials Clinical trial information is current as of For the most up-to-date information regarding a particular trial, search by NCT ID. NCT : Phase II study of ponatinib for advanced cancers with genomic alterations in fibroblastic growth factor receptor (FGFR) and other genomic targets (KIT, PDGFRa, RET FLT3, ABL1) RET aberration Second line or greater/refractory/relapsed, Stage IV II ponatinib OH The Ohio State University Comprehensive Cancer Center [ ]

29 TEST DESCRIPTION Oncofocus is a next -g eneration sequencing (NGS) based test that detects genomic alterations in ca ncer -related genes. Test results are intended to aid in patient management when used in conjunctio n with standard cl inical as sessment. The test is neither intended nor validated for diagnosis HOTSPOT GENES COPY NUMBER VARIANTS FUSION DRIVERS AKT1 ALK AR BRAF CDK4 CTNNB1 DDR2 EGFR ERBB2 ERBB3 ERBB4 ESR1 FGFR2 FGFR3 GNA11 GNAQ HRAS IDH1 IDH2 JAK1 JAK2 JAK3 KIT KRAS MAP2K1 MAP2K2 MET MTOR NRAS PDGFRA PIK3CA RAF1 RET ROS1 SMO ALK AR BRAF CCND1 CDK4 CDK6 EGFR ERBB2 FGFR1 FGFR2 FGFR3 FGFR4 KIT KRAS MET MYC MYCN PDGFRA PIK3CA ABL1 AKT3 ALK AXL BRAF EGFR ERBB2 ERG ETV1 ETV4 ETV5 FGFR1 FGFR2 FGFR3 MET NTRK1 NTRK2 NTRK3 PDGFRA PPARG RAF1 RET ROS1 CNV FUSION HOTSPOT HOTSPOT + FUSION HOTSPOT + CNV CNV + FUSION HOTSPOT + CNV + FUSION Additional tests for targeted therapies available. Please visit

30 APPENDIX Test Performance: Oncologica tests are intended for clinical use. The tests performance characteristics were validated and verified under controlled conditions by Oncologica UK Ltd, which operates quality management systems based on ISO-15189:2012 standards to perform high complexity testing. The tests have not been cleared or approved by the United States Food and Drug Administration; however, such clearance or approval is not currently required. Report: Information compiled in this report is from publicly available sources. By updating the source database quarterly, Oncologica is making every effort to provide the most accurate and up-to-date information. However, accuracy and completeness are not guaranteed and test reports, once issued, will not be updated. Interpretation is performed by both specialist Consultant Histopathologists and by Oncologica's team of State Registered Biomedical and Clinical Scientists. Interpretation is for the specific requested test only. No Guarantee: By providing drug and clinical trial information for the reported diagnosis, Oncologica is not guaranteeing that any drug or clinical trial is necessarily appropriate for this patient. Healthcare providers should evaluate and interpret the information provided in this report, along with all other available clinical information about this patient, to determine the best treatment decisions in their own independent medical judgment. Patient management decisions should not be based on a single test, including this one, nor solely on the information contained in this report. Alterations: This test identifies genomic alterations found in the submitted tumor tissue to select cancerassociated genes or portions of genes. While tested alterations were selected for inclusion in the test based on clinical level of evidence, Oncologica makes no claims regarding the clinical actionability of tested and reported alterations. Also note that this test only examines tumour, and not normal tissue from the patient, and therefore cannot distinguish between somatic and germline (i.e., heritable) alterations. Drugs: The drugs listed on the report are not ranked in any specific order as to predicted efficacy or appropriateness for this patient. Oncologica makes no guarantee or promise as to the effectiveness or suitability (or lack thereof) of any drug listed on this report. For more detailed information, healthcare providers should refer to the package insert for each FDA-approved drug listed in this report, and go to for information regarding drugs in clinical trials. Reimbursement: Oncologica makes no guarantee that any third party payor, including any governmental healthcare program, will pay for this test.

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