$1.3M Grant Will Advance Precision Medicine for Pediatric Cancer

November 25, 2020 - Children’s Hospital of Pennsylvania (CHOP) and Gustave Roussy, a cancer research organization based in France, have received a $1.3 million grant from neuroblastoma clinical research charities to develop precision medicine treatments for pediatric cancer.

The grant will support parallel phase 3 clinical trials developed by the Children’s Oncology Group (COG) and the International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN). The grant will be distributed over a four-year period and split between CHOP and Gustave Roussy.

Neuroblastoma is the most common pediatric cancer diagnosed in infancy, affecting approximately 90 percent of children before the age of five. In North America and Europe, about 1,500 children are diagnosed with severely malignant, high-risk neuroblastoma each year, which requires intensive treatment.

Fewer than half of those with high-risk disease live more than five years after diagnosis, and those who do survive often suffer from lifelong side effects, including hearing loss, learning disabilities, and secondary malignant cancers.

To develop more effective and less toxic treatments for neuroblastoma, clinical trials developed by COG and SIOPEN will leverage a precision medicine approach. Researchers will target mutations in the ALK oncogene, which are found in more than 14 percent or more of patients with newly diagnosed neuroblastoma and have recently been linked to relapses of the disease.

In collaboration with Pfizer Pharmaceuticals and the New Approaches to Neuroblastoma Therapy (NANT), researchers at CHOP have discovered a highly potent ALK inhibitor, called lorlatinib, which is currently used to treat lung cancer that would impede the pro-cancer activities of these ALK mutations and have a significant impact on neuroblastoma patients.

“This exciting collaboration is an important step in developing better treatments for children with neuroblastoma,” said Yael Mosse, MD, a physician-scientist who focuses on neuroblastoma in CHOP’s Cancer Center.

“Only one new drug has been approved by the FDA for neuroblastoma in the past 30 years. We hope this collaboration between North American and European researchers will bring more targeted therapies to children newly diagnosed with this disease.”

In parallel phase 2 clinical trials within COG in North America and SIOPEN in Europe, researchers will aim to use lorlatinib to significantly improve survival in patients with newly diagnosed high-risk neuroblastoma whose tumors have an activated ALK gene mutation.

The collaboration, called Transatlantic Integration Targeting ALK in Neuroblastoma (TITAN), will include simultaneous evaluation of the addition of lorlatinib to both COG’s and SIOPEN’s high-risk neuroblastoma treatment regimens, combining the data with the aim of accelerating lorlatinib approval if the drug is effective.

“This collaboration will allow us to evaluate a targeted therapy upfront in combination with the standard treatment developed by COG and SIOPEN for children with high-risk neuroblastoma. It is a unique opportunity to demonstrate the impact of such targeted therapies in this disease,” said Dominique Valteau-Couanet, MD, PhD, the division chief of Pediatric Oncology at Gustave Roussy.

“The collaboration is the result of a confident relationship developed between our two groups during the last decade. This trial is the first step of a collaboration that will help to answer questions that could not be solved otherwise.”

The grant will help advance precision medicine treatments for pediatric cancer patients, leading to more effective therapies and better outcomes.

“This is a landmark step in clinical research for children with neuroblastoma,” said Andy Pearson, MD, Chair of the Solving Kids’ Cancer UK Scientific Advisory Board, which managed the grant review and award process.

“With pediatric cancer hugely underfunded in comparison to adult cancer, there is an urgent need for breakthrough treatments for the most difficult-to-cure childhood cancers like neuroblastoma. This trial has the potential to accelerate the discovery of a new treatment and lay the foundation for future collaborations of this nature.”