• Spearheading the first European multi-modular academic clinical trial in Europe, VHIO announces the launch of its Basket of Baskets (BoB) endorsed by the Cancer Core Europe (CCE) Consortium.

 

  • Set to significantly advance basket trial design to-date, BoB will integrate molecular prescreening, the development of novel diagnostic tests including ctDNA, with the assessment of targeted therapies matched to those patients who will be most likely to benefit from them.

Timed to coincide with this week’s 4th Annual Meeting of the Cancer Core Europe Consortium (CCE), hosted by VHIO, we have announced the official launch of our Basket of Baskets (BoB) two-stage clinical study. Ringing in a pioneering approach in the design of so-called ‘basket’ studies, BoB promises a more flexible and adaptive model in order to significantly accelerate patients’ access to an array of novel therapeutics.

Jordi Rodón and Irene Braña, Associate Investigator and Phase I Investigator, respectively, of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa”, alongside our Unit’s Director and Principal Investigator of VHIO’s Early Clinical Drug Development Group, Elena Garralda, have now initiated this study within the framework of the Cancer Core Europe Consortium; a unique partnership aimed at addressing the cancer care and research continuum, of which VHIO is a Founding Member.

“Our innovative and adjustable trial design in ‘real time’, will facilitate earlier access for patients to matched novel therapies, without the need for independent studies assessing each individual tumor type, as has been the case until relatively recently,” said Jordi Rodón, who is also a Medical Oncologist and Clinical Investigator at the MD Anderson Cancer Center, Texas, USA.

The novelty of the Basket of Baskets (BoB) is its multi-modularity within the same trial, using the same diagnostic and screening tools. He continued, “This novel design will allow us to evaluate various alterations at the same time, as well as the efficacy of different drugs, either as monotherapy or in combination. Several baskets/modules and different treatments will therefore co-exist with a single molecular screening, which will optimize patient stratification and enrollment.”

One of the main challenges hampering progress against cancer is tumor diversity. Cancer is as clever as it is complex. Tumors are heterogeneous, molecularly diverse and evolve over time. Aimed at tackling tumor diversity head-on, clinical trial design is evolving from a fixed model, from phase I safety analysis to phase II initial study of efficacy, to flexible strategies allowing for modifications to a particular study’s protocol in order to integrate and apply accumulated findings as soon as possible and therefore accelerate the drug development process.

“It is consequently easier to apply these ‘live’ insights and more precisely refine the eligibility criteria, adjust sample size and the proportion of randomization, as well as consider additional treatments. This flexibility will allow us to significantly up the tempo in drug development processes,” observed Elena Garralda.

VHIO’s two-part basket

BoB is divided into two separate parts: advanced molecular diagnosis or screening, i-Profiler, and the therapeutic phase, i-Basket. In the former, patient tumor samples are analyzed for genetic profiling to identify the specific alterations of each individual tumor, followed by bioinformatics analyses to gauge the clinical relevance of a particular treatment tailored to these alterations, with the option of adding additional modules with other anti-cancer medicines currently under development.

This research is carried out using an array of validated tools and a 400-gene capture panel which will be updated as new modules are approved and incorporated in the study. The panel was designed by members of CCE including Ana Vivancos, Principal Investigator of VHIO’s Cancer Genomics Group.

Patients identified with the alteration/s included in BoB´s i-Basket phase, and who meet the inclusion criteria, enter this second part. Each module is focuses on a different treatment (either as monotherapy or in combination), and will have a different sponsor/coordinator. These different baskets can be co-financed by the pharmaceutical industry providing the selected drug, but always within the scope of academic sponsorship.

Every week, clinical researchers at each site will meet to discuss the implications of the molecular alterations identified in each patient, so that joint decisions can be taken regarding next steps.

This process will be facilitated by a new platform developed by Cancer Core Europe, in collaboration with Rodrigo Dienstmann, Principal Investigator of VHIO’s Oncology Data Science (ODysSey) Group). This tool facilitates patients’ data and their respective medical reports in order to better guide treatment decisions. This tool harmonizes the results of tumor analyses so that they can be studied as a whole, and also generates reports on the development of disease   by   specific molecular alteration,” explains Jordi.

 Identification of patients for enrollment in the first module is already underway at VHIO, Gustave Roussy Institute (Villejuif, France), Cambridge Cancer Centre (UK), and the Netherlands Cancer Institute – NKI (Amsterdam, The Netherlands), and will soon commence across other sites belonging to CCE members.

The first basket, now initiated, will assess the efficacy of immunotherapy in patients’ tumors with various genetic profiles, including mutations in the BRCA1/2, MLH1, MSH2, MSH6 or PMS2, POLE or POLD genes, as well as others related to DNA repair or tumors with high mutational levels. This module is co-financed by Roche Group (Switzerland).

“This is only the very first. We will seek to gradually add other modules as our study progresses, based on the alterations identified as shared targets in patients’ tumors from different parts of the body. This is the advantage of our novel approach. In fact, we are already talking with other pharmaceutical companies that are interested in including their anti-cancer medicines and co-financing modules,” concludes Irene Braña.

At VHIO, the BoB trial is being carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa”, the hub of VHIO’s early clinical drug development, which is supported by one of our private patrons, the Fundació Bancària “la Caixa”.

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To discover more about what our BoB study co-designers have to say on the rapidly evolving landscape of clinical trial design in the era of precision oncology, we invite you to browse the following article that was recently published in Molecular Oncology:

Elena Garralda, Rodrigo Dienstmann, Alex Piris, Irene Braña, Jordi Rodon, Josep Tabernero.New clinical trial designs in the era of Precision Medicine. Molec Oncol, 2019.  https://doi.org/10.1002/1878-0261.12465.