The U.S. Food and Drug Administration (FDA) has approved larotrectinib, the first oral TRK inhibitor, under the brand name Vitrakvi®. The approval is for the treatment of adult and pediatric patients with solid tumors with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or have progressed following treatment. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Larotrectinib is the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval. In clinical trials of patients with TRK fusion cancer, larotrectinib demonstrated an ORR of 75 percent (N=55) (95% CI: 61, 85%), including a 22 percent complete response (CR) rate.
"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. 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," said David Hyman, M.D., chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a global principal investigator for a larotrectinib clinical trial. "We now have the first therapy approved for this genomic alteration, regardless of cancer type."
NTRK gene fusions are genomic alterations that result in constitutively-activated chimeric TRK fusion proteins, which act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines. Larotrectinib, developed by Bayer and Loxo Oncology, Inc., is a CNS active TRK inhibitor designed to inhibit these proteins. TRK fusions can be found in many types of solid tumors and affect both children and adults. In the clinical trials that were the basis for this approval, larotrectinib showed clinical benefit across numerous unique tumor types, including lung, thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland and infantile fibrosarcoma.
"The first approval of larotrectinib is the culmination of years of hard work and research by many people to bring the first treatment to patients with TRK fusion cancer. TRK fusions are rare, but occur across many different tumor types. In this era of precision medicine, we are delivering on Bayer’s commitment to advance the future of cancer care while providing value for patients and physicians," said Robert LaCaze, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "It is very rewarding to provide a therapy specifically for patients with advanced solid tumors harboring an NTRK gene fusion."
"We are grateful to the investigators, research teams and patients who contributed to and participated in the larotrectinib clinical trials that supported this approval," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "It is now even more critical to screen patients of all ages with advanced solid tumors for actionable genomic insights that could benefit their care or aid in their referral to clinical trials."
TRK fusion cancer is diagnosed through the identification of NTRK gene fusions using specific tests, including those that employ next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH). Patients eligible for treatment with larotrectinib should be selected based on the presence of an NTRK gene fusion in their tumor.
"We welcome the FDA approval of larotrectinib and the innovations in genomic testing that make such precision medicine a reality," said Andrea Stern Ferri...
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