Bayer today announced that the European Commission has granted conditional marketing authorisation in the European Union (EU) for the targeted oncology treatment larotrectinib.

The drug is indicated for the treatment of adult and paediatric patients with solid tumours that display a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options.

A first-in-class oral TRK inhibitor designed to treat tumours that have an NTRK gene fusion, larotrectinib is the first treatment in the EU to receive a tumour-agnostic indication.

It is already licensed in the U.S., Brazil and Canada.

Dr Julia Chisholm, Consultant in Paediatric and Adolescent Oncology at The Royal Marsden Hospital, commented: “Larotrectinib’s EMA licencing marks another step towards treating cancers based on tumour genetics rather than site of origin in the body. Treatment with larotrectinib, which is designed specifically for the NTRK fusion oncogenic driver, can deliver clinically meaningful responses in patients with cancers which otherwise remain challenging to treat. We are delighted that clinicians managing such patients will now have a medicine licensed to specifically treat tumours with an NTRK gene fusion.”

Dr Julia Chisholm is currently Principal Investigator for the ongoing SCOUT study to test the safety and efficacy of the drug larotrectinib for the treatment of tumours with NTRK-fusion in children.

Genomic testing for NTRK gene fusions is key to identifying those patients who are most likely to benefit from targeted oncology medicines such as larotrectinib.

The medicine is indicated for the treatment of adult and paediatric patients with solid tumours that display a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options.

It demonstrated clinically meaningful responses in adults and children with TRK fusion cancer, including central nervous system (CNS) tumours. 

The EMA licensing of larotrectinib is based on pooled clinical trial data of 102 patients (93 patients from the primary analysis population and an additional 9 patients with primary CNS tumours) across the phase I trial of adult patients, the phase II NAVIGATE trial in adult and adolescent patients and the phase I/II paediatric SCOUT trial.

Results in the primary analysis population demonstrate an overall response rate (ORR) of 72% (95% CI: 62, 81).

In an additional analysis including primary CNS patients, the ORR was 67% (95% CI: 57, 76).

In the pooled primary analysis set, neither the median duration of response nor median progression free survival had been reached at time of analysis.

Larotrectinib showed a favourable safety profile, with the majority of adverse events (AEs) being grade 1 or 2.

Only 3% of patients had to permanently stop therapy due to treatment-emergent AEs.

TRK fusion cancer is rare overall, affecting no more than a few thousand patients across Europe annually.

It affects both children and adults and occurs in varying frequencies across various tumour types.

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein.

The altered protein, or TRK fusion protein, becomes constitutively active or over expressed, triggering a signalling cascade.

These TRK fusion proteins act as oncogenic drivers that fuel the spread and growth of the patients’ cancer, regardless of where it originates in the body.

Larotrectinib, an oral, highly selective TRK inhibitor, was investigated in clinical trials across 29 different histologies of solid tumours including lung, thyroid, melanoma, gastrointestinal stromal tumours, colon, soft tissue sarcomas, salivary gland and infantile fibrosarcoma.

The compound has shown efficacy in primary CNS tumours, as well as patients with brain metastases, across age or tumour histology.

Dr Brendon Gray, Medical Director at Bayer, said: “As the first tumour agnostic medicine licensed in Europe, larotrectinib represents a real shift in cancer treatment and creates an opportunity for the UK to demonstrate it is at the forefront of genomic medicine. Larotrectinib offers new treatment options for adult and paediatric patients, some of whom have had not treatment options to date.”

Source: Bayer