Lorlatinib ALK inhibitor pilot trials


(Sam Saffron) #1

In a call with @ludwinski she mentioned Pfizer are looking to trial Lorlatinib very very soon in some centers.

Lorlatinib has had some amazing initial results:

http://www.pfizer.com/news/press-release/press-release-detail/pfizer_presents_promising_data_from_next_generation_alk_ros1_inhibitor_in_advanced_non_small_cell_lung_cancer

http://nnbcr.se/2016/08/19/examination-of-a-new-putative-neuroblastoma-inhibitor/

Lorlatinib has increased activity towards ALK mutants prevalent in neuroblastoma examined in both in vitro kinase assays and cell-based experiments examining ALK mutations. In contrast to crizotinib, single agent administration of lorlatinib causes a dramatic tumor inhibition in mouse models of high-risk neuroblastoma. Taken together, the research groups show that lorlatinib is a potent inhibitor of crizotinib-resistant ALK mutations, and highlight an important new treatment option for neuroblastoma patients.

I was wondering if there are any more details about where this trial will run and who will have access?

This also raises the question about ALK testing in frontline, at the moment SIOPEN do not dictate ALK testing and only some COG centers that participate in the biology study will test.


High risk NB relapsed in the bones, seeking help and suggestions
2de relapse..we need your advise
(Sam Saffron) #2

I heard back from Dr. Maris

The lorlatinib trial was developed by my colleague here in Philadelphia Yael Mosse, and the trial will be conducted in the NANT, and include two European sites. It should open this spring. The trial is not yet on the NANT or ClinicalTrials.gov websites, but should be within a month or so as the contracts were completed last week.


(Sam Saffron) #3

More info about the upcoming clinical trial is here:

http://www.solvingkidscancer.org/the-latest/2017Lorlatinib

The phase I trial will be co-led by Dr. Yael Mossé at Children’s Hospital of Philadelphia (CHOP) and Dr. Araz Marachelian at Children’s Hospital of Los Angeles (CHLA), and will be conducted in 14 hospitals in the United States and Canada through the New Approaches to Neuroblastoma Therapy (NANT) consortium, as well as two European sites including Royal Marsden in London and Institut Curie in Paris. The study focuses on a subset of neuroblastoma patients with mutations in the anaplastic lymphoma kinase (ALK) gene. Abnormal ALK genes are found in 15 percent of high-risk neuroblastoma patients, and portend a very poor prognosis.


(Umut Özkırımlı) #4

Hi Sam
Any news on this trial?
They keep saying it is coming but nothing yet it seems.
Our son (stage 4, high risk myn-c, relapsed twice) has only that as a remaining option.
Thnks, Umut Ozkirimli


(Sam Saffron) #5

I strongly recommend you email or call CHOP and solving kids cancer, my understanding is that its just about to start (if it has not started yet)