Approved for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

An oral small molecule inhibitor.

A selective inhibitor of TRK (Neurotropic receptor tyrosine kinase) proteins

Chromosomal rearrangement involving fusions of NTRK genes may result in activated chimeric TRK fusion proteins, acting as an oncogenic driver promoting cellular proliferation and survival in malignancies.

TRK gene fusions are genetic alterations that appear across a wide range of tumors—including breast and colorectal cancer, infantile fibrosarcoma, lung cancer, melanoma, and various sarcomas, that lead to uncontrolled TRK signaling and tumor growth.

Such fusions are rare, but they are expressed in dozens of adult and pediatric tumor types.

More than 50 different partner genes that fuse with 1 of 3 TRK genes (NTRK 1, 2, and 3 have been recognized.

Trade name Vitrakvi.

In trials in patients with TRK-positive tumors it induced an objective response rate (ORR) of 75%, 7 (13%) complete responses, 34 (62%) partial responses, and 7 (13%) patients with stable disease (SD).

At 1 year, 71% of responses were ongoing.

More than half (55%) of patients remained progression-free at 1 year.

The breakdown by tumor type included: salivary gland, soft-tissue sarcoma, infantile fibrosarcoma, thyroid tumor, colon cancer, lung cancer, melanoma, cholangiocarcinoma, appendix tumor, breast cancer and pancreatic cancer.

The overall response rate by tumor type was salivary gland tumor (83%), other soft-tissue sarcoma (91%), infantile fibrosarcoma (100%), thyroid tumor (100%), colon cancer (25%), lung cancer (75%), melanoma (50%), GIST (100%), cholangiocarcinoma (best response, SD), appendix tumor (best response, SD), breast cancer (progressive disease), and pancreatic cancer (best response, SD).

Overall response rate was 75%, one year 71% of the responses were ongoing with 55% remaining progression free.

Overall, 22% had a complete response 53% obtained a partial response

The most common treatment-related adverse events (TRAEs) were increased ALT/AST level (38%), dizziness (25%), fatigue (16%), nausea (16%), constipation (16%), vomiting (11%), increased body weight (11%), anemia (9%), decreased neutrophil count (9%), and diarrhea (5%).

Does 100 mg twice a day in adults.

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