FDA grants breakthrough therapy designation to LOXO-101 for solid tumors with NTRK gene fusions

The FDA granted breakthrough therapy designation to LOXO-101 for the treatment of unresectable or metastatic solid tumors with neurotrophic tyrosine receptor kinase gene fusions, according to a press release from the agent’s manufacturer.

The designation applies to use of LOXO-101 (Loxo Oncology) for adults and children who require systemic therapy and who either progressed after prior treatment or for whom no viable alternative treatment exists.

LOXO-101, a selective inhibitor of tropomyosin receptor kinase, demonstrated clinical activity in patients with solid tumors with neurotrophic tyrosine receptor kinase (NTRK) gene fusions, according to study results presented in April at the American Association for Cancer Research Annual Meeting.

Investigators enrolled 41 patients with tumors refractory to other available therapies. Patients received LOXO-101 orally once or twice daily for continuous 28-day cycles.

Seven of the patients had gene fusions involving NTRK1 or NTRK3. Tumor types in this subset included non–small cell lung cancer, sarcoma, papillary thyroid cancer, gastrointestinal stromal tumor or mammary analog secretory carcinoma of the salivary glands.

At data cutoff, six of these seven patients were evaluable, and all six had demonstrated clinical response. Five had achieved confirmed partial responses defined by RECIST criteria. Researchers reported 21% tumor regression in the sixth patient.

The most frequently reported adverse events were grade 1 or grade 2 fatigue (29%), dizziness (24%) and nausea (20%).

A phase 2 basket trial is underway to evaluate LOXO-101 in adults with cancer whose tumors harbor TRK fusions.

“We’re pleased to have been granted breakthrough therapy designation for LOXO-101 and look forward to working more closely with the FDA to bring this therapy to patients with TRK fusion cancers,” Josh Bilenker, MD, CEO of Loxo Oncology, said in a press release. “Data presented to date from the ongoing adult and pediatric studies of LOXO-101 have demonstrated durable anti-tumor activity across TRK fusion cancers, further validating LOXO-101’s potential to address the unmet medical need among patients with these genetically defined cancers.”