Loxo's larotrectinib leads to high response rates in range of tumours with TRK fusions

Loxo Oncology said that interim data from three ongoing studies of the experimental oral drug larotrectinib, also known as LOXO-101, in patients whose tumours harbour tropomyosin receptor kinase (TRK) fusions demonstrated a 76 percent confirmed objective response rate (ORR) across tumour types. The results were presented at the ASCO annual meeting.

"Larotrectinib delivers consistent and durable responses in TRK fusion patients across all ages, regardless of tumour context, and does so with few side effects," remarked David Hyman, global principal investigator of the Phase II NAVIGATE trial. Hyman added "the larotrectinib TRK fusion story fulfills the promise of precision medicine, where tumour genetics rather than tumour site of origin define the treatment approach."

The analysis presented at the ASCO meeting included 50 TRK fusion patients enrolled in Loxo's Phase I adult trial, the NAVIGATE study and the Phase I/II SCOUT paediatric trial who had confirmed response data available. The company noted that the primary efficacy outcome measure for the analysis was ORR as measured by RECIST v 1.1, while key secondary goals include duration of response (DOR), progression-free survival (PFS) and safety.

Loxo said that the analysis revealed that 64 percent of patients had a partial response, with 12 percent having a complete response. In addition, 12 percent of patients had stable disease, with the remaining 12 percent of subjects having progressive disease. The drugmaker noted that in five of the six patients who initially responded to larotrectinib, but subsequently progressed, the resistance to the drug was due to the same secondary genetic alteration, known as a solvent front mutation. Loxo added that median DOR and PFS have not been reached.

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According to Loxo, results from the studies will be used in a marketing application that is expected to be submitted to the FDA in late 2017 or early 2018. The company indicated that the primary analysis for the filing will rely upon central, independent radiology review, which will be performed in the second half of 2017. For further analysis, see ViewPoints: Loxo Oncology builds case for being next in line for a genetically defined cancer approval.

Last year, larotrectinib received FDA breakthrough therapy status for the treatment of unresectable or metastatic solid tumours with NTRK-fusion proteins in adult and paediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments.

Commenting further on the results, Hyman said "I hope this raises the ambition of the field to go after targets without concern for their frequency." The analysis simultaneously measured larotrectinib's effectiveness in both children and adults, a first in the development of a cancer drug, and encompassed 17 different types of cancer, Hyman said.

Last month, the FDA approved Merck & Co.'s Keytruda (pembrolizumab) for the treatment of any metastatic microsatellite instability-high or mismatch repair deficient solid tumour, marking the first time the agency cleared a cancer drug based on the presence of a specific biomarker as opposed to its location in the body. For related analysis, read ViewPoints: One small step for Keytruda, one giant leap for personalised cancer care.

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