Roche reported Thursday promising results from a Phase I/II study of the experimental drug entrectinib in children and adolescents with recurrent or refractory solid tumours with and without NTRK, ROS1 or ALK gene fusions. Data from the STARTRK-NG trial, which will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting, showed responses in all paediatric tumour types harbouring the gene fusions, including those in the central nervous system (CNS).
Results demonstrated that entrectinib shrank tumours in all 11 children and adolescents who had NTRK, ROS1 or ALK fusion-positive solid tumours, including two subjects who achieved a complete response. Of the patients, five with primary high-grade tumours in the CNS had an objective response, including one patient with a complete response. In addition, partial responses were observed in nine patients, while Roche indicated that another patient with neuroblastoma and an ALK F1174L mutation achieved a complete response.
"It's stunning," remarked lead author Giles Robinson, adding "it speaks of the potency of targeted therapy when you have the target and the right drug." According to Robinson, between 1 percent to 2 percent of solid tumours in children might harbour the target mutations.
As of October 31 last year, the STARTRK-NG study enrolled 29 children and adolescents aged 4.9 months through to 20 years who had recurrent or refractory solid tumours, and 28 were evaluated for response. Roche noted that 11 of these patients were identified to have tumours with NTRK, ROS1 or ALK fusions and one with ALK F1174L-mutated neuroblastoma.
Sandra Horning, head of global product development, said the study "underscores the importance of combining comprehensive genomic profiling with targeted therapies." Recruitment in the study is ongoing, with enrolment into the Phase II portion set to start soon.
In February, the FDA granted priority review to Roche's marketing applications seeking approval of entrectinib to treat certain adult and paediatric patients with NTRK fusion-positive, locally advanced or metastatic solid tumours, and to treat patients with metastatic ROS1-positive non-small-cell lung cancer. The agency is expected to issue its decision on the oral drug, which Roche obtained through its $1.7-billion purchase of Ignyta in 2017, by August 18.
Last year, the FDA approved Bayer's oral TRK inhibitor Vitrakvi (larotrectinib) to treat adult and paediatric patients with tumours harbouring an NTRK gene fusion. Results to be presented by Bayer at the ASCO conference showed that in an expanded dataset of 34 paediatric patients, an overall response rate of 94 percent was seen, including 12 complete responses, 18 confirmed partial responses and two partial responses awaiting confirmation.
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