This exciting new clinical trial sees 17 transatlantic centres in the UK, USA and Europe, recruiting patients simultaneously for an innovative new third-generation ALK-inhibitor agent lorlatinib (PF-06463922).

Aimed at targeting mutated ALK genes often indicative of lower survival rates in children with neuroblastoma, the drug has shown minimal toxicity in adults and presents a low treatment burden for children as an oral tablet taken daily. Throughout the trial, there will be regular monitoring to assess for adverse events and efficacy but the amount of time spent in hospital for patients will be significantly less than they will have experienced during prior treatments.

Principal investigators: Lou Chesler, MD, Institute of Cancer Research; Yael Mosse, MD, Children’s Hospital of Philadelphia, Araz Marachelian, Children’s Hospital Los Angeles.

Project partners: Solving Kids’ Cancer (US); Children’s Neuroblastoma Cancer Foundation; Band of Parents; Evan’s Victory Against Neuroblastoma Foundation; The Ronan Thompson Foundation; Wade’s Army; The Catherine Elizabeth Blair Memorial Foundation.

Total project award: $400,000

Our grant award: £60,000

Date of award: September 2016

Study Protocol:


Targeting specific genes has proved a successful treatment method in many adult cancers, but less so in childhood cancers as there are fewer targets identified. A mutation in the ALK gene is one of these targets. Around 15% of children with neuroblastoma show this mutated gene at diagnosis, and about 20% at relapse.

Current treatments targeting ALK mutations in other cancers have not shown significant efficacy against neuroblastoma, due to the uniqueness of the mutations and acquired drug resistance. Researchers have discovered the cause of resistance in this type of neuroblastoma and have produced a ground-breaking new drug to overcome it. Lorlatinib has shown significant results in lab-based trials using patient-derived mouse models, even against the most resistant cell lines. The drug also passes the blood-brain barrier, vital in the treatment of highest-risk patients.

What difference will this project make?

Lorlatinib has the potential to be an effective treatment for neuroblastoma with ALK aberrations that have so far been resistant to other treatments. The project could potentially result in a new, low toxicity, frontline treatment for ALK-positive neuroblastoma patients. Dr Yael Mosse says"

“Lorlatinib has shown dramatic results in the lab against ALK+ neuroblastoma tumors in mice.” 

“If this trial proves successful, we expect the drug to quickly become part of frontline therapy in children with ALK-driven neuroblastoma – which is a tremendous accomplishment in cancer research, overall.”

What makes this project standout?

This trial is a unique collaboration between industry, academic consortium, and charities. Certain aspects of the trial design that are critical to the management of future therapies for children with neuroblastoma have been made possible by the charities, and it’s the charities’ support that has created access for children in three countries. This is imperative to drive rapid accrual and results, with the possibility of drug approval in USA and Europe in record time.

About the research team

Prof Louis Chesler, MD, PhD, is Honorary Consultant Medical Oncologist at The Royal Marsden and leads the Paediatric Solid Tumour Biology and Therapeutics within The Institute of Cancer Research’s Clinical Studies Division. He studied at undergraduate level at the University of Wisconsin-Madison and received his MD and PhD at Northwestern University and Medical School in Chicago. Prof Chesler is a member of the American Association for Cancer Research and the American Association of Paediatrics and is on the editorial board for several peer-reviewed journals. His focus is on developing new drugs for poor-outcome children’s cancers resistant to existing treatments.

Yael Mosse, MD, is attending physician at Children Hospital of Philadelphia’s Cancer Centre. She studied at undergraduate level at Smith College, Northampton, at graduate level at Hebrew University, Jerusalem, and received her MD from the Sackler School of Medicine in Tel Aviv. Dr Mosse is a member of the Abramson Cancer Center of the University of Pennsylvania, and of the Clinical Research Quality Assurance Committee, the Institutional Review Board, and the Genes Genomes and Paediatric Diseases Research Affinity Group at the Children’s Hospital of Philadelphia. Her area of expertise is neuroblastoma.


Our special thanks to Oscar, his parents Leona and Stephen, and all of #TeamOscar’s donors and fundraisers for helping to bring this clinical trial to fruition, continuing Oscar’s legacy.

“We are so thankful to the incredible #TeamOscar donors who continue to raise funds for research in partnership with Solving Kids’ Cancer in Oscar’s name. This has directly led to this innovative trial being made available to children in the UK, which will provide an option and hope to some families where previously there was none. Neuroblastoma is one of the most cruel and devastating childhood cancers, which urgently requires investment in research. There is nothing more devastating as a parent than reaching a point in your child’s cancer journey where there are no further treatment options. We reached this all too soon with our son Oscar, and are desperate to help ensure future families will not need to face this nightmare,”

Leona and Stephen Knox.