Promising Results in Tumor Shrinkage Study Announced at Neurofibromatosis Conference

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Over half of patients treated with selumetinib in phase I trial see reduction in plexiform neurofibromas

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As hundreds of the world’s leading NF experts convene in Monterey, California for the Children's Tumor Foundation NF Conference, the largest gathering dedicated to neurofibromatosis (NF), it was announced today that for the first time in the history of the treatment of plexiform neurofibromas (PNs), over 50% of patients saw decreased volume in these inoperable tumors. In a presentation titled “The Promise of MEK: Therapeutics for NF1”, Brigitte C. Widemann, MD, of the National Cancer Institute (NCI), reported that response data in a phase I trial for children and young adults is showing decreases in tumor volume. Anecdotal improvement in function, and reduction in PN related pain and disfigurement has also been observed.

Plexiform neurofibromas exhibit the most rapid growth in young children, and therefore early intervention in children with growing PNs may result in the greatest clinical benefit. Consistent volume decreases of large PNs has not been reported in the past, and today’s announcement indicates a promising future for the development of effective medical therapies for NF1 related PNs.

This highly successful clinical study is the result of a major investment of the Children’s Tumor Foundation NF Preclinical Consortium (funded since 2008). Nancy Ratner, PhD and Wade Clapp, MD demonstrated that MEK inhibitors (MEKi) have a massive result on PN tumor volume in mice.

“Today, this very robust effect of MEK inhibitors in mice with neurofibromas demonstrates the utility of the Ratner and Clapp NF animal models to select agents for clinical trials,” said Annette Bakker, PhD, President and Chief Scientific Officer of the Children’s Tumor Foundation. A registration trial of selumetinib for inoperable PN has been developed and will commence enrollment soon.

Neurofibromatosis, or NF, is a genetic disorder that can cause tumors to grow on nerves throughout the body, and may lead to a number of health issues, including deafness, blindness, learning disabilities, bone abnormalities, disabling pain, and sometimes cancer. Neurofibromatosis appears in three possible forms – NF1, NF2, and schwannomatosis – each with its own indications. Today’s announcement is most relevant for NF1, which appears in one in 3,000 people. There currently is no cure for NF, but the Foundation’s innovative research work is accelerating the path to treatments, as highlighted at its annual NF Conference, the premier gathering of NF experts and leading specialists in related disciplines such as neuroscience and oncology.

In her presentation, Dr. Widemann highlighted that the RAS/RAF/MAPK pathway is activated in NF1 related PNs, and that 16 of 24 patients treated with the MEK inhibitor selumetinib (AZD6244 hydrogen sulfate) saw a tumor volume decrease of ≥ 20% and clinical improvement. This result shows that NF research has made progress not only in the identification of active agents in the preclinical model, but also in the clinic as well.

Additional preclinical and clinical work will be ongoing to direct the future development of agents for NF1 PNs, and a phase II registration trial is in development which will include evaluation of patient reported outcome measures and functional measures, in addition to volumetric MRI analysis to evaluate if PN volume decreases can result in clinical improvement.

“It’s very exciting to be able to report this significant clinical progress in the development of effective treatment for NF1,” said Dr. Widemann. “NF patients are waiting for results, and through this trial of selumetinib, and the work of Nancy Ratner and Wade Clapp, who highlighted the utility of this model through their work with MEK inhibitors, we’re hopeful for the future. I’m especially grateful to the Children’s Tumor Foundation, Astra Zeneca, CTEP, the NCI and of course the participating patients for their support and/or funding of NF research, which is resulting in positive results for all patients with NF.”

“The success reported today by Dr. Widemann gives us hope”, said Annette Bakker, PhD, President and Chief Scientific Officer of the Children’s Tumor Foundation. “Our driving focus is on accelerating NF research through innovative collaborations, and Dr. Widemann’s incredible work with plexiform neurofibromas is a great example of this model, along with the investments in the preclinical consortia and the partnership with the REiNS Initiative (Response Evaluation in Neurofibromatosis and Schwannomatosis). REiNS provided selection of appropriate patient reported outcomes as well as the functional evaluations of this study. On behalf of the NF community of patients, we give big thanks and congratulations to Dr. Widemann for her success.”

Dr. Bakker added, “Today’s news is a big step on the path to what we all want – more clinical trials for patients, so they can lead better lives.”

To learn more about NF Conference, which runs through Tuesday, June 9, 2015, please visit

About Children’s Tumor Foundation
The Children's Tumor Foundation is a 501(c)(3) not-for-profit organization dedicated to finding effective treatments for the millions of people worldwide living with neurofibromatosis (NF), a term for three distinct disorders: NF1, NF2, and schwannomatosis. NF can cause tumors to grow on nerves throughout the body and may lead to blindness, bone abnormalities, cancer, deafness, disfigurement, learning disabilities, and excruciating and disabling pain. NF affects one in every 3,000 people, more than cystic fibrosis, Duchenne muscular dystrophy, and Huntington’s disease combined. The Children’s Tumor Foundation funds critical research into neurofibromatosis. In addition to benefiting those who live with NF, this research is shedding new light on several forms of cancer, brain tumors, bone abnormalities, and learning disabilities, ultimately benefiting the broader community. For more information, please visit

Children’s Tumor Foundation
Simon Vukelj, VP, Communications
svukelj(at)ctf(dot)org 212-344-7568

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Children's Tumor Foundation
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