WIN Consortium to Launch New Precision Oncology Study, Bank Samples for Blood Biomarker Discovery
Posted: Thursday, June 28, 2018
WIN Consortium to Launch New Precision Oncology Study, Bank Samples for Blood Biomarker Discovery
PARIS (Genomeweb) – The Worldwide Innovative Networking (WIN) Consortium at its annual symposium this week provided an update on its precision oncology clinical trial pipeline.
On the heels of reporting data from the WINTHER trial at the American Society of Clinical Oncology's annual meeting earlier this month, the consortium leadership this week discussed launching another study called MERCURY. Like WINTHER, this new trial will also use both DNA and RNA data to match patients with a variety of tumors types to targeted therapies and evaluate the impact of this approach on their outcomes.
The consortium has enrolled the first three patients into SPRING, a trial that is investigating the safety and efficacy of triplet therapies as a front-line option for advanced non-small cell lung cancer patients and will validate a biomarker algorithm for identifying which patients will benefit from these combinations. WIN is also close to launching a repository of blood and tissue samples, called BOOSTER, that will be used to discover and validate blood biomarkers for the early detection of NSCLC.
At ASCO, researchers presented data from WINTHER — WIN Consortium's first completed study —showing that the addition of transcriptomics to genomics allowed 35 percent of 303 consented advanced cancer patients to be matched to a treatment. Without the RNA-based algorithm, the match-rate would have been 23 percent.
Although the study did not meet its prespecified clinical benefit endpoint due to a number of factors, a blinded, post-hoc analysis showed that when patients received treatments they were most likely to benefit from as determined by high matching scores, they lived significantly longer compared to those who did not get the top-matched therapies. The study demonstrated the value of RNA data in precision oncology, the importance of gauging gene expression in tumor and normal samples, and that patients were willing to provide these samples.
WIN consortium is taking these lessons and incorporating them into MERCURY, a double-basket study that will enroll patients with a range of tumors, and match them to a variety of drug arms including single and combination agents based on genomic and transcriptomic profiling. Patients will be tested on a 270-gene next-generation sequencing panel and have their differential gene expression measured in normal and tumor tissues using HTG Molecular Diagnostics' nuclease assay.
The WINTHER algorithm will propose the best matches for each patient, and principal investigators will assign patients to a cohort guided by the match score and DNA data. For every drug/tumor arm, researchers will aim to enroll 10 patients in the first phase of MERCURY, and the arm will be expanded to the second phase only if two or more see their tumors shrink in the first four months of treatment. Cohorts that expand to the second phase will enroll another 18 patients. Seven or more patients will have to have a response in order for a particular therapy to be considered effective, and the drugs that yield the best responses will move on for evaluation in Phase III registration trials.
WIN is hoping to demonstrate that the basket study design will result in more efficient development of cancer drugs by advancing treatments with a higher chance of success in Phase III.
Highlighting MERCURY at the symposium, Richard Schilsky, chairman of WIN and chief medical officer of ASCO,noted that the attrition rate in oncology drug development is 82 percent and around 53 percent of kinase inhibitors fail. Moreover, in Phase III studies, 45 percent of drugs fail due to lack of efficacy and 24 percent don't succeed because they didn't extend survival compared to existing options.
SPRING
The lessons from the WINTHER trial are also important for SPRING, another WIN study the US Food and Drug Administration approved for launch last year. The proof-of-concept study will evaluate the safety and efficacy of triple therapies in advanced NSCLC patients, and retrospectively validate the ability of the SIMS algorithm, which integrates genomics and transcriptomics, to match patients to a combination therapeutic strategy.
In a 2015 Oncotarget paper, researchers led by Razelle Kurzrock, director of the Center for Personalized Cancer Therapy & Clinical Trials Office at the University of California, San Diego's Moores Cancer Center, described how they developed SIMS by analyzing lung tumor and normal tissue using targeted genomic sequencing and also looking at copy number variation,transcriptomics, and miRNA expression. Using these techniques, they identified 24
BOOSTER
Another area WIN is hoping to make an impact is in the area of blood-based diagnostic markers for NSCLC. With BOOSTER,