FDA Approves Larotrectinib for Treatment of Cancerous Tumors with NTRK Gene Fusion

The US Food and Drug Administration (FDA) has granted an accelerated approval to larotrectinib (Vitrakvi, Bayer and Loxo Oncology, Inc) for the treatment of pediatric and adult solid tumors with neurotrophic receptor tyrosine kinase (NTRK) gene fusion “without a known acquired resistance mutation, [and that] are metastatic or where surgical resection is likely to result in severe morbidity, and [for individuals who] have no satisfactory alternative treatments or that have progressed following treatment.”

At the time of initial FDA approval, larotrectinib— a central nervous system active TRK inhibitor engineered to inhibit these proteins—is the first treatment to receive a tumor-agnostic indication.

The overall response rate and duration of response served as the basis for the approval. An overall response rate of 75% (n = 55) (95% CI, 61%, 85%), which includes a 22% complete response rate and 53% response rate, was demonstrated with use of larotrectinib. In confirmatory trials, verification and description of clinical benefit may decide continued approval for this indication.

"The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene fusion—a rare driver of cancer,” David Hyman, MD, chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a global principal investigator for a larotrectinib clinical trial, said in a recent statement.

“I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type,” he continued. “We now have the first therapy approved for this genomic alteration, regardless of cancer type."

According to pooled data from a phase 1 adult trial, phase 2 NAVIGATE trial, and phase 1/2 pediatric SCOUT trial (n = 55), favorable complete and partial response rates were observed. Tumor types included soft tissue sarcoma, salivary gland, infantile fibrosarcoma, thyroid, lung, melanoma, colon, GIST, cholangiocarcinoma, appendix, breast and pancreas.

At the time of data cut-off, 73% of patients who received larotrectinib experienced a duration of response that lasted 6 months or more. At the time of analysis, the median duration of time and progression-free survival (1.84 months) had not yet been achieved.

Adverse events such as increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%) were observed in more than 20% of patients, regardless of attribution.

"We welcome the FDA approval of Vitrakvi and the innovations in genomic testing that make such precision medicine a reality," Andrea Stern Ferris, president and chief executive officer of the LUNGevity Foundation said in the statement. "We're seeing scientific advancements, like genomic testing capable of detecting an NTRK gene fusion, beginning to transform the treatment of cancer and provide new options for patients."