MErCuRIC – Year 3 Meeting

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.

 

NCRI 2016

MErCuRIC results were presented in a poster at the NCRI Cancer Conference in Liverpool, UK on 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’

Abstract

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.

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MErCuRIC Patient Representative with poster at NCRI

EUPATI Oct 2016 Newsletter

The latest newsletter from EUPATI is now available. This issue covers an update on national activities in 18 countries and information on the upcoming EUPATI 2016 conference All Aboard to a Better Health Future on 14 Dec 2016.

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MErCuRIC at ESMO16

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

Video on Liquid Biopsies from UNITO

Technologies to isolate and analyse liquid biopsy samples are rapidly evolving. MErCuRIC researcher Federica Di Nicolantonio discusses the technique in this video produced with ESMO.

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EUPATI Summer 2016 Newsletter

The summer 2016 newsletter for the European Patients’ Academy (EUPATI) is now available. In this issue, you can access the Patient Expert Training Course, now available in English, as well as learn about the growing national EUPATI teams that function as patient involvement groups locally.

EUPATI summer 2016

Prof. Bardelli Elected President of the EACR

Congratulations to Prof. Alberto Bardelli of UNITO on his election as President of the European Association for Cancer Research (EACR)!

You can read more here.

Bardelli EACR Aug 2016

MErCuRIC members serving the interests of upcoming young talents in oncology – the future of our profession

While the ever-advancing landscape of precision medicine in oncology undoubtedly brings fresh hope for patients, it also poses many yet unanswered questions as to how we move forward, without the real risk of burn-out of those who treat them – particularly with regards to the up-and- coming generation of young oncologists, the future of our profession and practice.

Established in 2001, the Young Oncologists Committee (YOC) of the European Society for Medical Oncology (ESMO) focuses on identifying real solutions matched to responding to the needs of more junior colleagues to relieve the burden they face and thus avert the real threat of some of the brightest future talents ultimately exiting from oncology.

Just one of the Committee´s major achievements marked to-date was the European-wide survey on burnout in young oncologists presented during the ESMO 2014 Congress in Madrid by YOC member and lead author Susana Banerjee. The survey evidenced that as many as 84% of respondents suffer in central Europe, compared with over 50% in the North. Despite these variations, the best case scenario of half of the respondents clearly represents a major problem. Thanks to the YOC, important steps are thankfully being taken to help reverse this alarming trend.

YOC is currently chaired by Matthias Preusser, Medical University of Vienna (Austria), and mentored by Josep Tabernero, Director of the Vall d´Hebron Institute of Oncology (VHIO), Barcelona (Spain), ESMO President-Elect, and PI of MErCuRIC´s future multicenter phase II study. It both devises and leads important educational and scientific programs aimed at delivering on the requirements of young oncologists in today´s era of precision science and medicine against cancer. YOC´s inspired range of activities and platforms include the Young Oncologists Corner, Journal Club, Preceptorship meetings, and special Young Oncologist sessions at national oncology congresses and ESMO specialty meetings.

Concerning the latter, Guillem Argilés, Medical Oncologist and Clinical Researcher of VHIO´s Gastrointestinal & Endocrine Tumors Group headed by Josep Tabernero, and a MErCuRIC phase II study co-collaborator, recently led an ESMO Session entitled Focus on Young Medical Oncologists during one of the Society´s leading annual oncology meetings: the 18 th World Congress on Gastrointestinal Cancer, 29 June – 02 July, Barcelona, Spain.

Co-chaired by Josep Tabernero, this unique educational opportunity paired a mentorship session with two scientific presentations delivered by young oncologists. More specifically, in mentorship, Eduardo Vilar Sanchez of the University of Texas MD Anderson Cancer Center, Houston (USA), provided participants with expert advice on how best to build a solid CV in the molecular oncology era and achieve a balance between bench and bedside, followed by invaluable pointers from Richard M. Goldberg, the Ohio State University Comprehensive Cancer Center, Columbus (USA), on how best to find a good mentor in GI oncology.

The second half of the session showcased latest research delivered by young oncologists Rodrigo Dienstmann, Principal Investigator of VHIO´s Oncology Data Science (ODysSey) Group, and Loredana Vecchione, the Netherlands Cancer Institute (NKI), Amsterdam (The Netherlands), who presented on the Clinical implications of transcriptional subtyping in mCRC, and Beyond NGS, towards functional prescreening models in therapeutic decisions in cancer, respectively.

“Divided into two parts, Mentorship and Scientific, this special session delivered on the main mission of ESMO´s Young Oncologists Committee by providing opportunity to strengthen young oncologists’ skills, knowledge and expertise, as well as a platform for networking with other medical oncologists and oncology professionals”, observes Guillem who was appointed as a Member of ESMO´s YOC back in January this year.

“Important actions implemented and developed thanks to the enthusiasm and drive of the YOC will undoubtedly continue to provide the necessary support and educational opportunity for ESMO´s younger members. As appointed Mentor of this Committee, I am devoted to guiding and flanking these dedicated efforts”, says Josep Tabernero.

Under the chairmanship of Matthias Preusser, Guillem and co-YOC members are currently finalizing the Young Oncologists (YO) Track at the forthcoming ESMO 2016 Congress, 07 – 11 October 2016, Copenhagen Denmark. Along with the extremely popular and established YO Track opportunities from previous ESMO Congresses including YO Brunch, Masterclass and Mentorship Sessions, the 2016 Vesalius Talk will focus on developing an effective collaboration between basic scientists and oncologists.

To discover more about ESMO, its Young Oncologists Committee, the recently celebrated 18 th World Congress on Gastrointestinal Cancer, well as the forthcoming ESMO 2016 Congress, visit: www.esmo.org.
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Josep Tabernero, Director of the Vall d´Hebron Institute of Oncology (VHIO), ESMO President-Elect, and PI of MErCuRIC´s future multicenter phase II study

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Guillem Argilés, Medical Oncologist and Clinical Researcher of VHIO´s Gastrointestinal & Endocrine Tumors Group and a MErCuRIC phase II study co-collaborator

Delivering 21st Century Medicine for bowel cancer patients

In June 2016, the Northern Ireland Cancer Research Consumer Forum and its Bowel Cancer Research Interest Group hosted a public event – ‘Delivering 21st Century Medicine for bowel cancer patients’.

A MErCuRIC poster was displayed at the event in Belfast. The event was opened by a member of the Local Assembly and speakers included MErCuRIC researcher Prof. Mark Lawler, who talked about precision medicine. During the break, the audience also had the opportunity to visit bowel cancer information stands.

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