A hand-pick of highlights to mark VHIO´s 2016 ASCO experience

To mark the recent close of the bustling Annual Meeting of the American Society of Clinical Oncology, Chicago 03 – 07 June 2016, we hand-pick just a few of the many VHIO studies that were selected to showcase throughout the course of the premier international conference in clinical oncology that year on year, draws a global attendance of over 30.000 leading oncologists.

Not only did exciting new data from VHIO first-outing throughout the poster discussions and sessions, but some findings were also selected by the ASCO Meeting´s Scientific Committee as oral presentations delivered during corresponding Clinical Science Symposia. One such study led by Rodrigo Dienstmann, Principal Investigator of VHIO´s Oncology Data Science (ODysSey) Group, evidenced the clinical relevance of clonal mutations in colorectal cancer for the very first time – findings that VHIO selected to promote through its ASCO-related media activity in addition to results from a Phase II trial demonstrating the clinical gains of combinatorial therapy with BRAF inhibitors for patients with advanced BRAF-mutated colorectal cancer, headed by VHIO´s Director Josep Tabernero.

Another VHIO oral presented during a Clinical Science Symposium themed Expect the Unexpected: Challenges in the Interpretation of Multiplex Panels, surrounded latest research championed by Judith Balmaña, Principal Investigator of VHIO´s High Risk & Cancer Prevention Group — for further details see our final pick below.

Just a few of the many VHIO highlights during ASCO 2016:

Central Nervous System Tumors

Jordi Rodón, Principal Investigator of VHIO´s Early Clinical Drug Development Group and Director and Medical Coordinator of our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa”, presented data from a first-in-human Phase I dose escalation study in patients with advanced glioma. Results revealed a safety profile classic of PI3K/mTOR-inhibitors and evidenced that molecule GDC-0084 successfully crosses the blood brain barrier (BBB) with uniform distribution throughout the brain — a promising BBB penetrating inhibitor for patients with advanced glioblastoma.

Dedicated to pioneering first-in-human studies and combinations of targeted therapies, biomarker-driven trials, and studies in molecularly selected populations, this particular study is also representative of how VHIO leads early drug discovery and development aimed at empowering current and future medicines against cancer.

Head and Neck Cancer

Neus Basté, Medical Oncologist and Clinical Researcher of VHIO´s Thoracic Tumors & Head and Neck Cancer Group directed by Enriqueta Felip, presented a study pioneered by VHIO researchers and physician scientists to explore the impact of VHIO´s prescreening efforts, driven by Ana Vivancos´ Cancer Genomics Group, on precision medicine against recurrent or metastatic head and neck cancers – encompassing highly heterogeneous tumor types for which chemotherapy has limited effect. The molecular profiling of head and neck cancer patients performed by VHIO teams using disease-orientated mutation panels for NGS panels and nCounter Nanostring – co-developed in partnership with VHIO´s Early Clinical Drug Development Group, not only identified those patients who are most likely to benefit from selected therapy but also ultimately unmasks potential new treatment targets for these difficult-to-treat tumors.

VHIO´s prescreening program of mutations in patients who are candidates for our portfolio of Phase I clinical trials carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa” is nucleated around the activity of VHIO´s Cancer Genomics and Molecular Oncology Groups. Performing molecular profiling in over 1500 patients per year, we assess the molecular make-up of each patient which affords us vital insights regarding the suitability for enrollment in clinical studies aimed at testing the efficacy of novel anti-cancer therapeutics.

Gastrointestinal (Noncolorectal) Cancer

Cholangiocarcinoma, although relatively rare, is another difficult-to-treat tumor type with few therapeutic options available. It generally goes undetected until symptoms present at advanced stages of disease and the efficacy of chemotherapy proves limited.

Presented by Tamara Sauri, Medical Oncologist and Clinical Researcher of VHIO´s Gastrointestinal & Endocrine Tumors Group, headed by Josep Tabernero, results from a study involving several VHIO teams including our prescreening program, demonstrated the molecular heterogeneity of biliary tract cancers (BTC) using a variety of different molecular tests. The molecular profiling of over 100 patients with metastatic BTC not only provided an expanded identification of driver alterations in these patients but also consequently afforded them the opportunity to participate in Phase I trials with matched targeted therapies.

This study represents another example of how VHIO, by adopting a purely translational, multidisciplinary research model, continues to deliver on the promise of precision medicine for an increasing number of our patients.

Clinical Pharmacology and Experimental Therapeutics

Presented during a poster discussion session dedicated to Developmental Therapeutics, results from the Phase Ib POSEIDON trial evidenced both the safety and the anti-tumor activity of therapy combining the experimental P13K inhibitor taselisib with tamoxifen in patients with HR positive, HER2-negative metastatic breast cancer. These early phase results demonstrated that the twinning of taselisib with tamoxifen was well tolerated and that this combo showed promising anti-tumor activity tracked through circulating tumor DNA.

Performed across three different sites; the Cambridge Cancer Center (Cambridge, UK), Netherlands Cancer Institute (NKI, Amsterdam, The Netherlands), and Vall d´Hebron Institute of Oncology (VHIO, Barcelona, Spain), this academic trial was carried out in collaboration with the European Commission 7th Framework Programme-supported EurocanPlatform and the RATHER – Rational Therapy for Breast Cancer consortia – both of which VHIO has been participant from the very outset.

Josep Tabernero, Director of VHIO, Cristina Saura, Principal Investigator of VHIO´s Breast Cancer and Melanoma Group, Javier Cortés, Associate Translational Investigator, and Mafalda Oliveira, Medical Oncologist and Clinical Investigator of the same group, all participated in this study.

A second study, as a VHIO tour de force multidisciplinary collaboration, was presented by Juan Martin, Phase I Researcher of VHIO´s Early Clinical Drug Development Group headed by Jordi Rodón. The study explored VHIO´s experience to-date concerning the predictability of P13K/AKT/mTOR (PAM) pathways and targeted therapies in gauging clinical benefit in early clinical trials. Upon analysis across various tumor types including colorectal, breast, and gynecological cancer, results demonstrated that single agent PAM inhibitors show the greatest potential for clinical benefit by mutation and treatment matching in non-colorectal patients – insights that will better steer patient selection for specific therapies.

Developmental Therapeutics – Immunotherapy

Despite the promising clinical activity of novel immunotherapeutics against various tumor types marked to-date, an important number of patients either develop resistance to therapy or clinical benefit varies greatly. Alejandro Navarro, Medical Oncologist of VHIO´s Thoracic Tumors and Head & Neck Cancers led by Enriqueta Felip, presented latest findings from research carried out in collaboration with other VHIO groups and colleagues at the Hospital Clínic Barcelona, showing the predictive ability of immune-related gene expression in advanced lung cancer, head and neck, and melanoma to help identify patients likely to manifest resistance to anti-PD1/PDL1 immunotherapy, regardless of tumor type or cancer immunotherapy selected.

Given that one of the biggest challenges in cancer therapeutics today is to combat disease resistance and halt disease progression on or after therapy, such data will be important in better equipping the oncology community to overcome these major obstacles and advance novel immunotherapeutic strategies.

Cancer Prevention, Hereditary Genetics, and Epidemiology

During one of ASCO´s Clinical Science Symposia entitled Expect the Unexpected: Challenges in the Interpretation of Multiplex Panels, Judith Balmaña, Principal Investigator of VHIO´s High Risk & Cancer Prevention Group, presented conclusions of a multi-center study aimed at identifying genetic test results with conflicting interpretations in a prospective registry of multiplex testing (PROMPT), performed in collaboration with colleagues at the University of Pennsylvania (Philadelphia, USA), Memorial Sloan Kettering Cancer Center (New York, USA), Dana-Farber Cancer Institute (Boston, USA), Mayo Clinic (Rochester, USA), and the University of Pennsylvania Perelman School of Medicine (Philadelphia, USA). Their research analyzed conflicting interpretations and reporting of test results from massively parallel sequencing (MPS) of different commercial laboratories. MPS facilitates simultaneous testing of multiple genes associated with cancer susceptibility and therefore represents critical weaponry in genetic medicine against cancer.

Results revealed that a quarter of the findings reported in the PROMPT registry identified by multiplex panel testing provide a conflicting interpretation of clinical pathogenicity. This discovery should spur collaborative action aimed at both identifying and rectifying the reasons behind such discrepancies in variant classification as well as strive for homogenization of their interpretation.

As demonstrated through our pick of VHIO findings presented at ASCO 2016, VHIO´s approach to advancing cancer science, treatment and care, mirrors the overarching theme of this year´s ASCO meeting: Collective Wisdom – the Future of Patient-Centered Care and Research. More specifically, to accelerate advancements in oncology VHIO is committed to combining strengths and overcoming current challenges in collaboration. Collective participation at leading international meetings, our cross-border alliances and partnerships undoubtedly contribute to rendering anti-cancer therapeutics more precise — for increasingly more patients.

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For additional information surrounding VHIO´s research teams and current cancer discovery please contact: Amanda Wren, Director of Communications, Vall d´Hebron Institute of Oncology (VHIO), Email:awren@vhio.net, Tel. +34 695207886.

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