2022 in a nutshell: ACCELERATE’s journey to advance innovative therapies for childhood cancer

With the end of the year always comes the exercise of reflection. What challenges have I encountered? What solutions have I found? What are my goals for the upcoming year? ACCELERATE did not want to lag behind, and has also done the exercise: here is an overview of all achievements and future projects.

Annual Conference 2022

More than 350 people attended the ACCELERATE Annual Conference virtually on February 11-12, 2022. The event was filled with engaging discussions leading to the development of the 2022 Scientific Work Plan. Take a look at the summaries of the Breakout Sessions:

• Optimizing Industry / Academia partnerships
• Accelerating development of combination regimens in frontline therapy
• Innovation after a first paediatric regulatory approval
• When is a Randomized Clinical Trial not required for registration?

9th Paediatric Strategy Forum for Medicinal Product Development in MAPK pathway inhibitors

The 9^th Forum was held virtually on 28 and 29 March with 206 participants: 98 international paediatric oncology experts, 47 representatives from ten pharmaceutical companies in Europe and the US, 14 patient advocates from Europe, the US and Canada, 25 regulators from the EMA and national competent authorities within the EU regulatory network, European Health Technology Assessment [HTA] bodies, US FDA and Health Canada as observers. Read the manuscript with all the conclusions of the Forum.

Highlights of the Forum:

• Mitogen-activated protein kinase pathway is an important target in glioma, Langerhans cell histiocytosis, neurofibroma and leukaemia.
• Mitogen-activated protein kinase inhibitors can address many unmet needs and have demonstrated activity.
• Combination development and monotherapy optimisation is required.
• New clinical/functional end-points should be agreed prospectively with regulators.
• Inclusion in front-line studies and generating regulatory data are priorities.

Prioritisation Meeting on Menin Inhibitors

The prioritization meeting was held on the 6^th of June virtually and amongst the conclusions, it was agreed that there is a clear, strong biological rationale, definitive pre-clinical data promising early clinical data that supports further evaluation of the activity of menin inhibitors in acute leukaemias. Menin inhibitors have the potential to address unmet needs in poor prognosis paediatric subtypes, including infant KMT2A-r ALL, high risk KMT2A-r AML and NUP98-r AML. Paediatric development of menin inhibitor-based strategies thus needs to be rapid. However, these are all rare populations and overall, one third of all patients with MLL KMT2A rearrangements are infants who have particularly unique challenges. As there are multiple products of the same class, a sequential approach is proposed. Menin inhibitors should move rapidly into front-line studies to be evaluated, especially infant leukaemia, as it is in this setting where there is the greatest unmet clinical need. A further meeting will be arranged to review the landscape and facilitate decisions in the field when more clinical and translational research data are available from the adult and paediatric populations. Read the summary of the meeting.

ALADDIN educational programme on strategic and regulatory science in paediatric oncology drug development

ACCELERATE and the 11 members of the ALADDIN consortium have launched a new educational program on strategic and regulatory science in paediatric oncology drug development to foster expertise and strengthen true multi-stakeholder collaboration.

What does ALADDIN have to offer?

• Course on Strategic/Regulatory Science in Paediatric Oncology Drug Development
• 360º Multi-stakeholder Rotation at the European Medicines Agency (EMA) and/or pharmaceutical industry (Roche or Sanofi)
• ACCELERATE Research Fellowship
• Online Educational Training Platform

Registrations for the Training Course, Rotations and Fellowship have now closed, but the Online Educational Portal will be launched soon. It will be free and open for everyone, providing access to videos, articles, and other educational content. Take a look at the webpage, subscribe to the newsletter, and stay tuned!

Fit For Filing Webinars - ACCELERATE Fit For Filing Working Group

Academic trials are not usually part of the marketing authorisation process of a new drug. But why is that? The “Improving academia-industry collaborative trials” webinar series explores how we can open up this opportunity to enable academia-industry collaborative trials to deliver data that can be used for licensing purposes (fit for filing). You can now watch the recording of the three webinars!

• Should and could my trial be fit for filing: Let’s explore how we can enable collaborative trials to deliver data that are fit for filing.
• A spoonful of data helps the medicine go down: Purposeful collection of clean and reproducible trial data: Early collaboration and communication between all stakeholders is crucial to develop better trial protocols and to collect adequate data and documentation.
• With great trial needs comes great responsibilities: Delivering high quality data and successfully file an application: Why does data quality and traceability matter? Are you getting what you pay for? What resources are required for running a Fit For Filing trial?

10th Paediatric Strategy Forum for DNA Damage Pathway Inhibitors

The meeting was help on 27 and 28 October in Amsterdam, at the European Medicines Agency headquarters. The manuscript summarizing all the outcomes is in the making – stay tuned!

The Forum focused on MAPK pathway inhibitors in paediatric tumours and malignancies and addressed the key issues in the ongoing development of inhibitors of the MAPK pathway in paediatric oncology. This includes prioritization of medicinal products, identifying the optimal combinations, dosing schedules and treatment duration in the landscape of current unmet needs while acknowledging biological differences in tumours. The importance of the use of appropriate methodologies to detect the molecular targets and evaluate responses to therapy, the crucial importance of formulation, different pharmacokinetics and pharmacodynamic properties including central nervous system penetration and short- and long-term toxicities were also reviewed.

Intercontinental collaboration workshop

ACCELERATE held a multistakeholder workshop on intercontinental collaboration, one of the objectives of the ACCELERATE International Collaboration Working Group. The Group conducted 30 surveys to trial teams (industry and academia) and 6 main hurdles were identified: lack of funding and heterogeneity of resources across countries, regulatory non-alignment, contracts, differences in standard of care, trial database, and lack of patient advocates’ involvement. There was a good discussion across these areas, with some very clear ideas on how to address some of the key issues. A manuscript will follow summarizing all the outcomes.

New publications

• Impact of the EU Paediatric Medicine Regulation on new anti-cancer medicines for the treatment of children and adolescents
• ACCELERATE Paediatric Strategy Forums: an advance for oncological drug development?
• Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors
• The Critical Role of Academic Clinical Trials in Pediatric Cancer Drug Approvals: Design, Conduct, and Fit for Purpose Data for Positive Regulatory Decisions
• Paediatric Strategy Forum for medicinal product development of multi-targeted kinase inhibitors in bone sarcomas
• ACCELERATE – Five years accelerating cancer drug development for children and adolescents

During 2022 ACCELERATE achieved many goals, but there is still a long way to go. 2023 will start with the 11^th ACCELERATE Annual Conference to be held on February 9-10. During the Conference, priorities for the year will be set and the Scientific Working Plan will be developed.

Three Paediatric Strategy Forums will be held on 2023. The first, focused on Medicinal Product Development of PI3K/AKT/mTOR Pathway Inhibitors in children and adolescents, will be held on April 3-4 at the Dana-Farber Cancer Institute headquarters in Boston, Massachusetts.

Many more engaging events are in the pipeline - Subscribe to our newsletter and stay runed! Let’s ACCELERATE the development of innovative therapies for children and adolescents with cancer together.