FDA News

FDA approves Vitrakvi for solid tumors with NTRK gene fusion

The FDA granted accelerated approval to larotrectinib for the treatment of adults and children with solid tumors that have a neurotrophic receptor tyrosine kinase gene fusion without a known acquired resistance mutation.

The approval applies to use of larotrectinib (Vitrakvi; Bayer, Loxo Oncology) for patients who have metastatic disease or for whom surgical resection likely will result in severe morbidity, and who either progressed after treatment or have no satisfactory alternative treatments.

Larotrectinib is the first treatment approved for neurotrophic receptor tyrosine kinase (NTRK) gene fusion cancers. It also is the first treatment to receive a tumor-agnostic indication at the time of its initial FDA approval.

“[This] approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body,” FDA Commissioner Scott Gottlieb, MD, said in a press release. “This new site-agnostic oncology therapy isn’t specific to a cancer arising in a particular body organ, such as breast or colon cancer. Its approval reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine. We now have the ability to make sure that the right patients get the right treatment at the right time.”

The FDA based the approval of larotrectinib — an oral TRK inhibitor — on pooled results of three trials that included a combined 55 adults and pediatric patients with NTRK gene fusion cancers, including soft tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer, lung cancer, melanoma, colon cancer, gastrointestinal stromal tumor, appendix cancer, breast cancer and pancreatic cancer.

Results showed a 75% overall response rate, a 22% complete response rate and a 53% partial response rate across various tumor types.

Of the 41 patients who achieved response, 73% remained in response for 6 months or longer at the time of data cutoff. Median duration of response and median PFS had not been reached. Median time to response was 1.84 months.

“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 principal investigator for a larotrectinib clinical trial, said in a Loxo Oncology-issued press release. “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.”

Adverse events reported among more than 20% of larotrectinib-treated patients included increased alanine transaminase (45%), increased aspartate transaminase (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%) and diarrhea (22%).

The FDA approved larotrectinib under priority review. The agency previously granted the agent breakthrough therapy designation, rare pediatric disease designation and orphan drug designation.

The FDA granted accelerated approval to larotrectinib for the treatment of adults and children with solid tumors that have a neurotrophic receptor tyrosine kinase gene fusion without a known acquired resistance mutation.

The approval applies to use of larotrectinib (Vitrakvi; Bayer, Loxo Oncology) for patients who have metastatic disease or for whom surgical resection likely will result in severe morbidity, and who either progressed after treatment or have no satisfactory alternative treatments.

Larotrectinib is the first treatment approved for neurotrophic receptor tyrosine kinase (NTRK) gene fusion cancers. It also is the first treatment to receive a tumor-agnostic indication at the time of its initial FDA approval.

“[This] approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body,” FDA Commissioner Scott Gottlieb, MD, said in a press release. “This new site-agnostic oncology therapy isn’t specific to a cancer arising in a particular body organ, such as breast or colon cancer. Its approval reflects advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine. We now have the ability to make sure that the right patients get the right treatment at the right time.”

The FDA based the approval of larotrectinib — an oral TRK inhibitor — on pooled results of three trials that included a combined 55 adults and pediatric patients with NTRK gene fusion cancers, including soft tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer, lung cancer, melanoma, colon cancer, gastrointestinal stromal tumor, appendix cancer, breast cancer and pancreatic cancer.

Results showed a 75% overall response rate, a 22% complete response rate and a 53% partial response rate across various tumor types.

Of the 41 patients who achieved response, 73% remained in response for 6 months or longer at the time of data cutoff. Median duration of response and median PFS had not been reached. Median time to response was 1.84 months.

“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 principal investigator for a larotrectinib clinical trial, said in a Loxo Oncology-issued press release. “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.”

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Adverse events reported among more than 20% of larotrectinib-treated patients included increased alanine transaminase (45%), increased aspartate transaminase (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%) and diarrhea (22%).

The FDA approved larotrectinib under priority review. The agency previously granted the agent breakthrough therapy designation, rare pediatric disease designation and orphan drug designation.