20 March 2020

Two New Clinical Proof-of-Concept Projects Funded by Oncode Institute

Bianca-Olivia Nita

Oncode Institute aims to link fundamental and clinical research to enable efficient translation of promising findings into novel diagnostic methods and clinical treatment strategies. We are pleased to announce that the 9thand 10th grant within the Clinical Proof of Concept programme have been awarded:

- Oncode Investigators Hugo Snippert, Hans Bos and Medical Oncologist Jeanine Roodhart (all part of UMC Utrecht) will work on a clinical intervention trial to evaluate a novel triple combination to treat colorectal cancer.

- Oncode Investigator Monique den Boer, together with clinicians Josef Vormoor, Peter Hoogerbrugge, Michel Zwaan and researchers Judith Boer and Olaf Heidenreich (all part of Princess Máxima Center) will work on a project to improve the clinical outcome and reduce side-effects for children with hematological malignancies.

In this article, we explain the two projects in more detail.

1. RASTRIC trial: Mutant Ras metastatic colorectal cancer triple drug combination therapy

The RAS gene is frequently mutated in colorectal cancer. Despite many attempts world-wide, targeted therapies for RAS mutant tumors have been unsuccessful so far. Using patient-derived organoids (PDOs) from RAS mutant colorectal cancers, the laboratory of Oncode Investigators Hugo Snippert in collaboration with Hans Bos (both Center for Molecular Medicine, UMC Utrecht), discovered a combination of three existing anti-cancer drugs that is successful in mice. A phase 1/2a clinical trial to test the beneficial effect of this triple combination in patients with RAS mutant colorectal cancers was designed by Jeanine Roodhart, medical oncologist in the UMC Utrecht, and approved by Oncode for financial support. The investigators aim to start the trial in the UMC Utrecht this summer.

Oncode Investigator Hugo Snippert says: “We are very happy with the help and support of Oncode to translate results from our fundamental research to patients; this is a prime example of the added value of the Oncode Institute”. Jeanine Roodhart adds: “Our phase 1/2a clinical trial is a step further in finding a treatment that could benefit patients with colorectal cancer in the future.”

2. International concerted action to refer children with relapsed and refractory leukemia/lymphoma to the right precision medicines trials: A platform for rational treatment choice based on molecular profiling and drug sensitivity testing

Children with hematological malignancies are treated according to standardized treatment protocols monitored by national childhood oncology study groups. Over the past decades, improvements in outcome were driven by the optimization of multi-agent chemotherapy regimens, minimal residual disease (MRD) monitoring, and (cyto)genetic prognostic markers including IKZF1 deletion and BCR-ABL1 fusion. However, relapses still occur in 15% of all cases and up to 40-50% of high-risk cases, and the outcome after relapse is poor. Contradictory, children with relapsed leukemia and lymphoma are treated with virtually the same drugs as those used in initial treatment, simply because detection of target presence for precision medicines and/or knowledge about resistance-modifying agents is lacking.

The objectives of Monique and her team are to determine the actionable lesions in a uniform setting by a group of experts, and to advice the treating physicians which trials are open in order to facilitate the enrolment of the right patient in the right early clinical trial.

Monique den Boer says: “Thanks to this project we can initiate an international molecular tumor board for leukaemia’s in children, to discuss which patients may be eligible for early clinical studies, whereas if we would do this on a national level there would only be a limited number of patients per country.

The funding is essential to initiate this process in a European context, which will have a catalytic effect on the exchange of knowledge between biological and clinical experts needed to initiate new trials and enrol the right patients in the right clinical trials. Moreover, this study will also document why certain patients are not enrolled in early clinical trials, which is essential to rethink drug development strategies for children with leukaemia.”

Marlinde Smit Programme Manager

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