A collaborative framework to perform ‘cancer therapy response integrative profiling’ (cTRIP) for melanoma patients treated with immune and targeted therapy

A collaborative framework to perform ‘cancer therapy response integrative profiling’ (cTRIP) for melanoma patients treated with immune and targeted therapy

Project Duration: 2018

MOHCCN Consortium: Marathon of Hope - Quebec

Investigators:  Ian Watson (GCI) and John Stagg (CHUM)

Co-PIs (alphabetical order by institution): Rahima Jamal (CHUM); Réjean Lapointe (CHUM); Francis Rodier (CHUM); Bertrand Routy (CHUM); John Stagg (CHUM); Simon Turcotte (CHUM); Alain Bergeron (CHUQ); Joël Claveau (CHUQ); Martine Perigny (CHUQ); Émilie Perron (CHUQ); Christoph Borchers. (JGH); Margaret Redpath (JGH); Sonia del Rincon (JGH); April Rose (JGH); Wilson Miller (JGH); Alan Spatz (JGH); Rene Zahedi (JGH); Peter Siegel (GCI); Lambert Busque (HMR); Christopher Rudd (HMR); Guillaume Bourque (MGC); Hamed Najafabadi (MGC); Ioannis Ragoussis (MGC); Yasser Riazalhosseini (MGC); May Chergui (MUHC); Sinziana Dumitra (MUHC); Marie-Christine Guiot (MUHC); Ari Meguerditchian (MUHC); Sarkis Meterissian (MUHC); Catalin Mihalcioiu (MUHC); Kevin Petrecca (MUHC); Keith Richardson (MUHC); Francine Tremblay (MUHC); Beatrice Wang (MUHC); Kevin Watters (MUHC); Kerry Savage (UBC)  

Partners: Centre hospitalier de l’Université de Montréal (CHUM); CHU de Québec - Université Laval (CHUQ); Jewish General Hospital (JGH); Goodman Cancer Institute (GCI); McGill Genome Centre (MGC); McGill University Health Centre (MUHC); University of British Columbia - BC Cancer Agency (UBC) 

Project goals:

The overall goal of this project is to:

  1. Discover and validate predictive biomarkers and signatures linked to immune therapy response and clinical outcomes for melanoma patients with our cancer therapy response integrative profiling’ (cTRIP) platform;
  2. Elucidate the mechanistic relationship between biological, tumoral and immunological modulation impacting treatment efficacy;
  3. Identify biological, tumoral and immunological features involved in immunotherapy-related adverse events (irAEs);
  4. Evaluate the effects of targeted therapies on the tumor-intrinsic and peripheral immune landscape of melanoma

Summary:

Major strides in the treatment of advanced melanoma were achieved with the approval of therapies targeting the MAPK pathway and immune checkpoints inhibitors (ICI), which are now standard of care for melanoma. While these treatments have shown impressive clinical efficacy with durable responses, more than half of advanced melanoma patients do not respond. We still lack a clear understanding of the tumor-intrinsic and systemic features associated with response to ICIs. There has been no direct comparison of the efficacy of proposed biomarkers for ICI from a multi-platform molecular characterization analysis of melanomas, circulating tumor and immune cells and the microbiome from a single cohort.

This project was started in 2018 as part of the TFRI MoHCCN Montreal Cancer Consortium (MCC) Pilot Project. The MCC allowed for the establishment and support of three melanoma biobanks, the “Banque de tissus, de sang et de données cliniques associées à des fins de recherche sur les mélanomes et autres cancers de la peau”, at the CHUM, the “Skin Lesion BioBank” at the MUHC and the Montreal Immune-Related Adverse Event biobank at the JGH. These three biobanks have already recruited more than 500 patients treated with ICI and targeted agents as standard of care or on clinical trials, with extensive longitudinal tissue and blood collection, obtention of archival FFPE tissue, stool and derived cell-lines, as well as complete clinical annotation.

This study will be instrumental for any MoHCCN initiatives focusing on immune therapy, providing real world evidence for immune therapy-treated patients.