April 2023: NANT investigators demonstrate that lorlatinib has potent anti-tumor effect in patients with neuroblastoma linked to a specific genetic alteration.
It is rare that a clinical trial is changed mid-investigation. But when results are striking enough, it can occur. Such striking results have been reported in a study led by the New Approaches to Neuroblastoma (NANT) pediatric cancer consortium, which is headquartered at Children’s Hospital Los Angeles (CHLA).
For patients with relapsed/refractory neuroblastoma with alterations in the ALK gene, lorlatinib has been shown to be a safe, effective targeted therapy. This finding—published in Nature Medicine—is so significant that the Children’s Oncology Group (COG) modified its phase 3 protocol to replace another ALK inhibitor (crizotinib) with lorlatinib to treat newly diagnosed neuroblastoma patients with an ALK alteration.
Araz Marachelian, MD, Medical Director of NANT’s Operations Center and CHLA’s Neuroblastoma MIBG Program, is the study’s sponsor and co-senior author on the Nature Medicine publication. “At NANT, we are pleased to have had a leadership role in this important discovery,” says Dr. Marachelian. NANT’s role included early collaboration on evaluating laboratory data, trial design, FDA approval, industry sponsorship, study oversight, safety monitoring, creating the study database, and analyzing and disseminating results. “We are thrilled to see many years of NANT’s planning and operation come to fruition with the results of this important study,” says Julie Park, MD, Chair of the NANT consortium. “Families are urgently waiting for new treatment possibilities like this one.” Dr. Park is an established neuroblastoma expert and chair of the Department of Oncology at St. Jude Children’s Research Hospital.
First author on the paper is Kelly C. Goldsmith of Children’s Healthcare of Atlanta and co-senior author is Yael P. Mosse of Children’s Hospital of Philadelphia. The trial was conducted at national and international sites including: Vanderbilt University Medical Center, Children’s Hospital Los Angeles (USC Keck School of Medicine), Children’s Hospital of Philadelphia, University of Iowa Hospital and Clinics, Children’s Hospital of Philadelphia, Stanford University School of Medicine, Perelman School of Medicine at the University of Pennsylvania, The Royal Marsden Hospital (London, UK), Cook Children’s Medical Center, University of Chicago, University of Michigan, Hospital for Sick Kids (Toronto, ON), Harvard Medical School, Children’s Hospital Colorado, Seattle Children’s Hospital, Institut Curie (Paris, France) and UCSF Benioff Children’s Hospital. The study was funded by National Cancer Institute grant P01CA217959, Pfizer Inc. and other grants and foundations.