Individualized Cancer Therapy: Chemotherapy Resistance Testing before Therapy

Transcription

1 Individualized Cancer Therapy: Chemotherapy Resistance Testing before Therapy 1 st st International Oncological Conference Wrocław, October 6 th, 2012 Dr. Frank Kischkel

2 Individualized Cancer Therapy: Drug Treatment Testing before Therapy 1 st st International Oncological Conference Wrocław, October 6 th, 2012 Dr. Frank Kischkel

3 Individualized Cancer Therapy: Drug Treatment Testing before Therapy Chemotherapy- Resistance-Test

4 Individualized Cancer Therapy Introduction Therapy Healing or Relief Diagnostics Cancer

5 Individualized Cancer Therapy Introduction CTR-Test ONCOMPASS TM Therapy Healing or Relief Diagnostics Cancer

6 Individualized Cancer Therapy Introduction Treatment Options Therapy Healing or Relief Diagnostics Cancer

7 Treatment Options for Cancer Introduction Irradiation Surgery Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Tumor Antibodies (monoclonal) Outside (Tumor) cells TC, VC, IC Immunotherapy Gene therapy Zytokines Immunomodulation IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system

8 Treatment Options for Cancer Introduction Irradiation Surgery Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Tumor Antibodies (monoclonal) Outside (Tumor) cells TC, VC, IC Immunotherapy Gene therapy Zytokines Immunomodulation IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system

9 CTR-Test Test can evaluate all drugs that act against cancer cells directly Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells Introduction TC TC TZ, VZ Antibodies (monoclonal) Zytokines Outside (Tumor) cells Immunomodulation TC, VC, IC IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system

10 ONCOMPASS Can Evaluate All Targeted Drugs Introduction Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Antibodies (monoclonal) Zytokines Outside (Tumor) cells Immunomodulation TC, VC, IC IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system

11 Chemotherapy- Resistance-Test CTR-Test

12 The Logistic Chain CTR-Test Tumor removal Transport Cancer patient Optimized Chemotherapy Duration: 7-9 days Chemotherapy- Resistance-Test Test result Oncologist

13 The Procedure CTR-Test Tumor Plating of Addition of Addition of preparation tumor cell chemotherapeutic 3H-labeled suspension drugs thymidine Different cell growth Isolation of genomic DNA Reading of incorporated 3H-activtiy Computing test result

14 The Test Report CTR-Test Standard distribution of a drug effect

15 CTR-Test The Test Report Drug A Slight Drug Resistance (SR) Medium Drug Resistance (MR) Extreme Drug Resistance (ER) Drug B Drug C Drug D Drug E Drug F Drug G -1 µ 1 2 Relative in vitro cell growth

16 Correlation of CTR-Test Test Result and Clinical Response CTR-Test N = 450, Overall response rate = 29% Slight Resistence Test result Relative in vitro cell gr rowth ER Medium Resistance Extreme Resistence Non-Responder Clinical Response Responder Kern DH, Weisenthal LM (1990) J Natl Cancer Inst. 82(7):582-8

17 Correlation of CTR -Test Result and Overall Survival CTR-Test Survival in % SR for platinum drugs (n-62) ER for platinum drugs (n-17) Time in months Holloway et al. (2002) Gynecologic Oncology 87(1):8-16

18 Extended Survival by Treatment According to Test Result CTR-Test Ovarian cancer, platinum-sensitive group Treatment according to test results (n = 31) Survival in % Treatment according to physician s choice (n = 31) Time in months Loizzi et al. (2003) Am J Obstet Gynecol 189(5):

19 CTR-Test Best Drug Combination Correlates with Single Active Drugs Kaplan-Meier progression free survival curves for patients with ER scores of 4 vs. 2-3 vs ER Score = 4 ER Score = 0-1 ER Score = 2-3 Mehta RS et al. (2001) Breast Cancer Research and Treatmant 66(3):

20 KPS DIAGNOSTICS GmbH

21 MOLECULAR ONCOLOGY REVOLUTION

22 FIRST PROSPECTIVE TREATMENT OF A EGFR MUTANT NSCLC PATIENT G FISH+SEQ Modern treatment of lung cancer: case 1. Amplification and mutation of the epidermal growth factor receptor in metastatic lung cancer with remission from gefitinib. Schwab R, Pinter F, Moldavy J, Papay J, Strausz J, Kopper L, Keri G, Pap A, Petak I, Oreskovich K, Mangel L. J Clin Oncol Oct 20;23(30):

23 RESPONSE TO EGFR INIBITORS IS INDEPENDENT FROM EGFR IHC Tissue- Clinical Gen. Smoker Sample Age EGFR TK Case TKI mutation Response Rtr 1 ADC 58 Fem. Never del inss gefitinib CR Analyis R e t r o s p P r o s p e k t í v Rtr 2 ADC 68 Fem. Never del erlotinib CR Rtr 3 adsq. c. 62 Fem. Smoker L858R erlotinib CR Rtr 4 ADC 66 Fem. Never del erlotinib PR Rtr 5 ADC 50 Male Never del insa erlotinib PR Rtr 6 ADC 65 Fem. Never L858R erlotinib PR Rtr 7 ADC 72 Fem. Never del erlotinib PR Rtr 8 anap. c. 54 Male Smoker del * erlotinib SD Pr 1 ADC 61 Fem. Never del insp gefitinib CR Pr 2 ADC 45 Fem. Never del insv gefitinib CR Pr 3 ADC 50 Male Smoker del inss erlotinib CR Pr 4 ADC 55 Fem. Never del erlotinib CR Pr 5 ADC 59 Fem. Never L858R gefitinib CR Pr 6 ADC 67 Fem. Never del erlotinib PR Pr 7 ADC 53 Fem. Never L858R erlotinib PR Pr 8 ADC 67 Male Never L858R erlotinib PR Pr 9 ADC 64 Fem. Never L858R erlotinib PR primer: Pr 10 ADC 55 Male Never L858R erlotinib PR, meta:

24 Molecular SAMPLE Diagnostic TYPES FOR MOLECULAR Platform PATHOLOGY BRUSH NEEDLE 26% LUNG 52% CT CYTOLOGY SMEAR 22% EXCISOR SURGICAL FFPE BLOCK COLON 10% ENDSOCOPY 90% SURGICAL LIVER METASTASIS 10% BIOPSY SURGICAL

25 SUCCESSFUL MULTIPLEX MOLECULAR PDX IN EXTREMELLY SMALL SAMPLES WITH ZEISS-PALM LASER CAPTURE MICROSCOPY BY TRANSFERING THE CELLS DIRECTLY FROM THE SLIDE TO THE PCR TUBE FOR AMPLIFICATION WITHOUT DNA EXTRACTION 100% LCM (ZEISS-PALM) OPTIMIZED DIRECT PCR MULTIPLEX XS-DX TM

26 DETECTION OF EGFR MUTATION IN 84 CELLS 28 db 56 db EGFR EXON 21 L858R Response to gefitinib therapy

27 NEXT GENERATION CLONAL SEQUENCING CAN PROVIDE HIGH THROUGHPUT INFORMATION ON POTENTIAL TARGETS AND ALSO ABOUT THE MOLECULAR HETEROGENICITY UP TO 1 MILLION PARALLEL PYROSEQUENCING UP TO 1000 BP READ LENGTH

28 3X 100% RESULTS IN RING TRIALS

29 ONCOMPASS TARGET 18 TARGETS 20 DRUGS ALK: BRAF EGFR: ERBB2/HER-2 ERBB4/HER-4 FLT3 KRAS HRAS NRAS KDR (VEGFR2) KIT PDGFR RET MET ABL SRC PIK3CA PTEN crizotinib vemurafenib erlotinib, gefitinib, cetuximab, panitumumab trastuzumab, lapatinib, pertuzumab, lapatinib sunitinib erlotinib, cetuximab, panitumumab cetuximab, panitumumab cetuximab, panitumumab pazopanib, sunitinib, sorafenib imatinib, sunitinib, dasatinib, nilotinib sunitinib, pasopanib, sorafenib vandetanib, sunitinib crizotinib imatinib, dasatinib, nilotinib dasatinib everolimus,temsirolimus, metformin, cetuximab, anti-eostrogens everolimus, metformin cetuximab, anti-eostrogens

30 ONCOMPASS DRUG SENSITIVITY DATABASE

31 ONCOMPASS TARGET-DRUG ASSOCIATION ANALYZER

32 ~100 TARGETS ~400 DRUGS WHICH DRUG? WHICH PATIENTS?

33 ONCOMPASS TARGETED CLINICAL TRIAL DATABASE CLINICAL TRIALS IN COLON CANCER PIK3CA MUTANT SOLID TUMORS CLINICAL TRIALS IN NSCLC PIK3CA MUTANT COLON CANCER BIOMARKER PIK3CA INHIBITORS ORGAN LINE TYPE OTHER MARKER.. PIK3CA BKM120 COLON 2nd Phase 1,II KRAS WT.. PIK3CA BYL719 SOLID TUMORS 2nd Phase I. PIK3CA M+/AMP.. PIK3CA temsirolimus SOLID TUMORS - Phase I PIK3CA/ PTEN M

34 ONCOMPASS TARGETED CLINICAL TRIAL NAVIGATOR AND PATIENT ASSISTANCE MET PDGFR EGFR HER-2 KIT AKT KRAS HRAS ALK NRAS PIK3CABRAF

35 Contact Data TherapySelect Dr. Frank Kischkel Carl-Bosch-Str Heidelberg, Germany Tel.: +49 (0) Fax: +49 (0) info@therapyselect.de