Initiated in 2011 by the EurocanPlatform and since 2016 organized under the umbrella of Cancer Core Europe, the Summer School in Translational Cancer Research will once again take place in Portugal in Albufeira, 16 – 20 October, 2017. The registration deadline is 30 June 2017.
You can learn more about the course here: https://dktk.dkfz.de/en/training/dktk-summer-school/introdution.
Applications are now being accepted for the third EUPATI Expert Training Course.
The EUPATI Training Course Patient Experts in Medicines Research & Development is an exciting and unique opportunity offering patient advocates expert-level training in medicines research and development, specifically tailored for them.
The application deadline is 31 March 2017.
Congratulations to Margaret Grayson, our MErCuRIC Patient Representative, who received a ‘Special Commendation’ for Research Engagement from Cancer Research UK in 2016!
The MErCuRIC team met at UZA in Antwerp for our Year 3 meeting (05 – 06 Dec 2016). We discussed progress in the Phase I trial from the previous year, and mapped our clinical and translational activities for the coming year. As the dose escalation phase I study draws to a close, we are planning activities to initiate the dose expansion phase I study. Samples from this study will soon be sent to the translational research partners for analysis.
MErCuRIC results were presented in a poster at the NCRI Cancer Conference in Liverpool, UK on 08 Nov 2016 (Session B, 08:15-11:00). The conference ‘showcases the latest basic, translational and clinical cancer research. It brings researchers together to share ideas and develop collaborations.’
‘MErCuRIC1: A Phase Ia study of MEK1/2 inhibitor PD-0325901 with cMET inhibitor crizotinib in patients with advanced solid tumours’
RAS activating mutations occur in ~55% of metastatic (m)CRC. RASMT and >50% of RASWT mCRC patients do not benefit from anti-EGFR antibodies. c-MET is overexpressed in ~50-60%, amplified in ~2-3% and mutated in ~1-3% of mCRC. Preclinical data support the clinical evaluation of MEK1/2 and METi, particularly in RASMT tumours and RASWT with aberrant c-MET expression. The study’s primary aim was to establish the maximum tolerated dose (MTD) and assess safety/toxicity profile of PD-0325901 MEKi/crizotinib METi in patients with advanced solid tumours using NCI CTCAE V4.03.
Method: A single arm, open-label phase I trial of PD-0325901 with crizotinib in patients with advanced solid tumours, measurable disease, ECOG PS 0-1 and adequate end organ function. Patients received oral PD-0325901 (days 1-21 every 28 days) at doses of 2-8mg BD with oral crizotinib continuously at 250mg OD or 200mg BD, using a rolling-6 design.Crizotinib started after a week lead-in with PD-0325901. Blood samples forpharmacokinetics, pERK and soluble c-MET levels and skin biopsies for pERK levels were collected.
Results: Between 12/2014 and 11/2015 we enrolled 25 patients; Male(13), Female(12), who received 52 cycles in total. Median age 63yrs (range 36-78). MTD was defined at the highest dose; crizotinib: 200mg BD continuously; PD-0325901: 8mg BD days 1-21 every 28 days at which 1/6 patients exhibited dose-limiting toxicity (fatigue). Drug-related adverse events were in keeping with single agent toxicity profiles, including rash, diarrhoea, fatigue, nausea, hypoalbuminemia and visual disturbances. Best clinical response was stable disease at end of cycle 2 in 4/25 patients.
Conclusion: MEK/METi can be given together at pharmacologically active doses. MTD for the PD-0325901/crizotinib combination was 8mg BD (days1-21) and 200mg BD continuously in a 28 day cycle. The combination is now being explored further with an alternate MEKi before expansion into RASMT and RASWT CRC with aberrant c-MET expression.EudraCT: 2014-000463-40.
MErCuRIC Patient Representative with poster at NCRI
The MErCuRIC Phase I trial was presented at the ESMO 2016 Congress in Copenhagen (7 – 11 Oct 2016).
MErCuRIC1: A phase 1a study of MEK1/2 inhibitor PD-0325901 with cMET inhibitor crizotinib in patients with advanced solid tumours (Poster: 480P)
R. Wilson, M. Middleton, J. Houlden, S. Van Schaeybroeck, C. Rolfo, E. Elez, J. Taieb , T. André, A. Bardelli , P. Laurent-Puig, J. Tabernero, M. Peeters, T. Maughan, C. Roberts, S. Love, M. Lawler , M. Salto-Tellez, M. Grayson, V. Popovici, F. Di Nicolantonio
MErCuRIC is funded by the European Community’s Framework Programme Seven (FP7) under contract #602901. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.