WSG future trials ADAPT TN2 ADAPT HER2. PreCycle. 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 2

Transkript

1 WSG Future trials 1

2 WSG future trials ADAPT TN2 ADAPT HER2 PreCycle 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 2

3 WSG future trials ADAPT TN2 ADAPT HER2 PreCycle 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 3

4 TNBC Neoadjuvante Chemotherapie beim TNBC (G6) TNBC + HER2 TNBC 36,9% 53,2% N=157 N=158 Von Minckwitz et al., Lancet Oncology WSG GmbH Confidential 4

5 ADAPT-TN1 Überlegenheit einer platin- vs. Gemcitabinbasierten Chemotherapie Gluz et al., ASCO WSG GmbH Confidential 5

6 TNBC Carboplatin neoadjuant verbessert DFS 3 yrs DFS 85.8% Proportion disease-free Logrank p= yrs DFS 76.1% HR PMCb to PM = 0.56, 95% CI (0.33,0.96), p= PM 36/157 events PMCb 21/158 events PM PMCb DFS, months Von Minckwitz et al., SABCS WSG GmbH Confidential 6

7 TNBC Platin-basierte Therapiestrategien GeparOcto ADAPT-TN Therapie-INTENSIVIERUNG Therapie-DEESKALATION WSG GmbH Confidential 7

8 TNBC Zielgerichtete Therapieansätze Tumorimmunologie / Checkpoint-Inhibition PARP-Inhibition Androgenrezeptor- Hemmung WSG GmbH Confidential 8

9 Synthetische Lethalität Grundlage für den Wirkmechanismus von PARP-Inhibition BRCA1 1 2 Genetic Mutation Somatic Mutation Karzinogenesis 1 PARP1 Iatrogenic Inhibition Cell death 2 Iatrogenic Inhibition WSG GmbH Confidential 9

10 PARP-Inhibition Wirksamkeit beim TNBC Rugo et al., SABCS 2012 Gelmon et al., Lancet Oncol WSG GmbH Confidential 10

11 ADAPT-TN2 Wissenschaftliche Rationale Identification of early markers of response for (i) platinum-based chemotherapy and (ii) PARP inhibition Optimization of novel chemotherapy regimens/combinations, i.e. validation of nab-paclitaxel/carboplatin chemotherapy as one optimal backbone for patients with TNBC Identification of patient subgroups with primary drug resistance who would potentially benefit from an early addition of targeted agents such as PARP inhibitors Identification of optimal veliparib dosing 11

12 ADAPT-TN2 Einschlusskriterien Inclusion Criteria TN breastcancer (ER-, PR-, HER2-) All N T1-4a-c Preoperative treatment is mandatory Questions: Carboplatin nab-paclitaxel backbone vs. two doses of Veliparib plus backbone Identification of early responders WSG GmbH Confidential 12

13 ADAPT-TN2 Geplantes Design Endpoint pcr C=Control N_C EOT R N_B pcr B N_A pcr A EOT Prognosis Estimation Three weeks therapy Efficacy Estimation B I O P S Y B I O P S Y B: Veliparib 50 mg/bid A: Veliparib 150 mg/bid nab-paclitaxel Carboplatin 125 mg/m 2 AUC WSG GmbH Confidential 13

14 ADAPT-TN2 Studienendpunkte Primary Endpoints Comparison: pcr in nab-paclitaxel/carbo vs. combined Nab-paclitaxel/Veliparib Arms One-sided test: powered for difference of 15% in pcr (α=0.05) Comparison: pcr in nab-paclitaxel/carbo vs. N_A and N_B Arms One-sided test: powered for difference of 18% each in pcr (a=0.01) Secondary Enpoints Exploratory test of N_B vs. N_A Identification of early responders Toxicity Translational research WSG GmbH Confidential 14

15 WSG future trials ADAPT TN2 ADAPT HER2 PreCycle 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 15

16 HER2+/HR- and HER+/HR+ are different entities.. HER2+/HR+ (TP) HER2+/HR- T-DM1 +/- ET vs T + ET 376 pat recruited in 2.5 yrs Oral presentation ASCO 15 Oral presentation SABCS 15 publication T+ P ± Taxane 134 patients randomized in 1.5 yrs study prematurely closed after interim analysis primary endpoint reached ASCO 2016 publication

17 Study design: HER2+/HR+ (n=209) Surgery R Incl. prognosis B I O P S I E Three weeks therpay Incl. eficacy B I O P S I E Trastuzumab Loading 8mg/kg then 6mg/kg Pertuzumab Loading 840 mg then 420 mg Paclitaxel 80 mg/m² Endocrine therapy 17

18 Study design: HER2+/HR+ (n=209) until week 52 until year 5 R Surgery Taxane-4xEC* plus Trastuzumab and Pertuzumab ** Trastuzumab + Pertuzumab Follow-Up 4xEC* plus Trastuzumab and Pertuzumab ** Plus adjuvant endocrine therapy** Incl. prognosis Three weeks therpay Incl. eficacy B I O P S I E B I O P S I E *at Investigator decision ** Currently Trastuzumab is standard of care in the adjuvant setting. Pertuzumab as double blockade will be included at time of positive APHINITY readout 18

19 WSG future trials ADAPT TN2 ADAPT HER2 PreCycle 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 19

20 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Denis et al., ASCO

21 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Denis et al., ASCO

22 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Denis et al., ASCO

23 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Denis et al., ASCO

24 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Denis et al., ASCO

25 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen Basch E et al. J Clin Oncol. 2016;34(6): /14/2016 WSG STUDIENTREFFEN WSG GmbH 25

26 Patient Reported Outcome (PRO) im klinischen Alltag Verbesserung der Versorgung anhand von Patientenrückmeldungen 41% 34% Therapiedauer (Mittel, p=0,002) Usual Care 6,3 Monate STAR 8,2 Monate Basch E et al. J Clin Oncol. 2016;34(6): /14/2016 WSG STUDIENTREFFEN WSG GmbH 26

27 CANKADO The different PRO modules 2 Drug intake Multi-lingual (adherence) Per intake, International daily Collaboration Symptoms and Management of adverse effects (based on CTCAE 4.0) PRO Daily Pain scale Daily Quality of Life (QoL) Daily, weekly or other intervals possible Dynamic Questionnaires Daily, weekly or other intervals possible 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 27

28 Physicians control all patient specific setting and features All settings are bundled in a single page for fast and easy handling 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 28

29 6 Ways for epro-measures Optimized to support older and younger patients On-Site (before meeting the physician) Nurse guided Provided PC, Tablet or CANKADO Terminals Patient s Smartphone CANKADO Terminal Off-Site (from at home or away) Weekly (PC, Tablet, Smartphone) Daily (PC, Tablet, Smartphone) Triggered (Web/APP from Q3/16) 11/14/ /14/2016 CANKADO Achieving more together WSG STUDIENTREFFEN WSG GmbH 29 29

30 Multi-Language support Each user can select his language independent 11/14/ CANKADO Achieving more together 30 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 30

31 CANKADO ist... gemeinnützig gebührenfrei für Patienten und Ärzte Verbesserung von Adherenz, QoL, Akzeptanz, Verständnis Generierung und Verarbeitung von Big-data Telemedizin ein offener Entwicklungs- und Forschungsverbund geeignet für Routineversorgung und zur Anwendung innerhalb von klinischen Studien 31

32 CANKADO ist NICHT... 32

33 PreCycle Impact of ehealth-support on Quality of Life in metastatic breast cancer patients treated by Palbociclib and endocrine therapy Sponsor: palleos Industry partner: Pfizer Study groups: AGO-B, AGO-TRAFO, DGHO, WSG Countries involved : Germany Planned Sites: 80 Planned Patients : 960 plus SF Recruitment Period: 2-2,5 years Planned study start: Q Indication Metastatic breast cancer of HR+/HER2- subtype 33

34 PreCycle Impact of ehealth-support on Quality of Life in metastatic breast cancer patients treated by Palbociclib and endocrine therapy Involvierte Gruppen: Studiensponsoren / operations: 34

35 PreCycle Impact of ehealth-support on Quality of Life in metastatic breast cancer patients treated by Palbociclib and endocrine therapy Hr+/Her2- metastatic breast cancer 1st line & 2nd-n line Inclusion Criteria as indicated by drug label/soc 35

36 PreCycle Impact of ehealth-support on Quality of Life in metastatic breast cancer patients treated by Palbociclib and endocrine therapy Study objectives Assess the impact of an ehealth-supported therapy management on Quality of Life in patients with HR+, HER2-advanced/metastatic breast cancer treated with CDK4/6 Inhibitor in combination with the endocrine therapies As ehealth-approach the High-Density Observation technology CANKADO-HDOB is used, which is intended for big data deep learning of patient reported outcome (PRO). Accompanying translational research program to assess biomarker with the ability to identify predictive markers for adherence, symptoms, response, and resistance 36

37 WSG future trials ADAPT TN2 ADAPT HER2 PreCycle 11/14/2016 WSG STUDIENTREFFEN WSG GmbH 37