FDA Allows WIN to Proceed with Targeted Tri-Therapy Clinical Trial in First Line Treatment
Posted: Wednesday, August 09, 2017
FDA Allows WIN Consortium to Proceed with Targeted Tri-Therapy Clinical Trial in First Line Treatment of Metastatic Non Small Cell Lung Cancer
VILLEJUIF, France--(BUSINESS WIRE)-- WIN Consortium (WIN) received the US Food and Drug Administration (FDA)’s approval to start the clinical investigation of a novel therapeutic approach using a combination of three targeted therapies for the first line treatment of patients with advanced Non Small Cell Lung Cancer (NSCLC). The Survival Prolongation by Rationale Innovative Genomics (SPRING) trial will aim to enroll patients who are usually offered first line platinum-based chemotherapy. Patients with documented targetable driver alterations (EGFR mutations, ALK rearrangements, ROS1 and MET exon 14 skipping mutations) will be excluded. The population of NSCLC patients without actionable oncogenic driver mutations, envisioned for the enrollment in SPRING trial, represents the vast majority of patients with metastatic NSCLC (~80% in the Caucasian population).
With over 60% of NSCLC detected in an advanced or metastatic stage, and less than 5% of patients alive at 5 years, a paradigm changing strategy for treating the deadliest cancer is needed. WIN’s novel approach is based on the utilization of the tri-therapy combination of targeted drugs, following the historical success of this approach in AIDS and tuberculosis. Similarly, our concept relies on the association of three targeted drugs that used in combination are expected to be highly potent, whereas used alone in monotherapy they produce only modest clinical outcome.
"Nevertheless, it is important to acknowledge a significant difference between cancer and AIDS which lies in the higher biological complexity and heterogeneity of cancer compared to AIDS. In AIDS, one tri-therapy combination is effective for a majority of patients, whereas in cancer it is expected that many combinations will be needed to treat all patients effectively. WIN Consortium has developed new technologies for tailoring combinations for each individual patient" said Dr. John Mendelsohn, Chairman of WIN. "WIN’s trial, entitled SPRING, is therefore a first proof of concept of this novel approach in the treatment of lung cancer, and will test as a first combination three drugs from WIN’s big pharma members, Merck’s Avelumab combined with Pfizer’s Palbociclib and Axitinib" added Dr. Mendelsohn.
SPRING’s investigator initiated research will be led by Dr. Razelle Kurzrock (University of California San Diego, Moores Cancer Center) and co-led by Dr. Enriqueta Felip (Vall d'Hebron Institute of Oncology) and is planned to be launched in 5 countries and 8 WIN member sites: University of California San Diego Moores Cancer Center and Avera Cancer Institute (Dr. Benjamin Solomon), USA; Institut Curie (Dr. Nicolas Girard), Centre Léon Bérard (Dr. Pierre Saintigny) and Hôpital Paris Saint-Joseph (Dr. Eric Raymond), France; Vall d'Hebron Institute of Oncology, Spain; Centre Hospitalier de Luxembourg (Dr. Guy Berchem); and Chaim Sheba Medical Center (Dr. Jair Bar), Israel.
The SPRING trial will start with a Phase I portion to explore the safety of the combination and determine the optimal doses for the Phase II that will explore the efficacy of this tri-therapy regimen in first line treatment of metastatic NSCLC. The trial will also aim to validate a novel algorithm SIMS (Simplified Interventional Mapping System) developed by WIN and designed to match each patient’s tumor biology to a specific drug combination. For this purpose, both tumor and normal lung tissue biopsies will be obtained and explored in the SPRING trial. DNA and RNA analysis will be performed by Dr. Brandon Young at Avera WIN Precision Oncology Laboratory in San Marcos, California on biopsies using, respectively, Illumina NGS (next generation sequencing) and HTG Molecular’s expression (mRNA and microRNA) EdgeSeq technology used in conjuction with Illumina (NGS). Data integration for the SIMS algorithm will be performed by Ben-Gurion University of the Negev (Dr. Eitan Rubin), Israel.
"It is an unprecedented cooperation between our WIN members from academia, industry and research organizations" said Dr. Vladimir Lazar, WIN Chief Scientific and Operating Officer. "Eight clinical sites will activate the study, drugs will be provided by Pfizer Inc., DNA and RNA analysis technologies by Illumina and HTG Molecular and pharmacovigilance by Covance. In particular, we are grateful to Foundation ARC on cancer research in France for financial support to initiate the SPRING trial. We are welcoming the support of any other organization or private donors, wishing to join this unique global effort dedicated to lung cancer patients" added Dr. Lazar.
"It is very exciting to see this endeavor becoming more concrete and this unprecedented cooperation materializing. We are looking forward to the activation of our clinical sites. We will need more combinations to be launched rapidly and other pharma companies to join us in this effort", said Dr. Razelle Kurzrock, trial global coordinator, and Head of WIN Clinical Trials Committee. "WIN has the potential and expertise to test other combinations and has the technologies needed to match patients’ tumor biology profile with the appropriate combination”.
About the WIN Consortium
WIN Consortium is a French based non-profit network of 41 world-class academic medical centers, industries (pharmaceutical and diagnostic companies), health payer, research organizations and foundation and patient advocates spanning 17 countries and 4 continents, aligned to deliver now the progress in cancer treatment that is awaited by so many patients and families around the world.
For further information, please visit www.winconsortium.org.
Director Operational Team
Vladimir Lazar, Tel: +33661091522
Chief Scientific and Operating Officer