FDA Approves This Drug for NTRK-Positive Advanced Solid Tumors

FDA Approves This Drug for NTRK-Positive Advanced Solid Tumors

(HealthDay News) — The U.S. Food and Drug Administration has approved Augtyro (repotrectinib), a next-generation tyrosine kinase inhibitor (TKI), for the treatment of patients with neurotrophic tyrosine receptor kinase (NTRK)-positive locally advanced or metastatic solid tumors.

Augtyro is approved for adult and pediatric patients (aged 12 years and older) with solid tumors that have an NTRK gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.

The approval was based on the TRIDENT-1, phase 1/2 trial, which included both TKI-naive and TKI-pretreated patients (40 and 48 individuals, respectively), collectively representing 15 different types of solid tumor cancer. During a median follow-up of 17.8 months, 58 percent of TKI-naive patients had a confirmed objective response rate (cORR), of whom 43 percent experienced partial responses and 15 percent had complete responses.

Among the TKI-naive responding patients, 83 percent were still in response at one year, and the median duration of response (mDOR) was not yet reached. During a median follow-up of 20.1 months, 50 percent of TKI-pretreated patients had a cORR, all of whom experienced partial responses and none of whom achieved complete responses. At one year, 42 percent of TKI-pretreated responding patients were still in response at one year and the mDOR was 9.9 months. Among the participants with measurable central nervous system metastases at baseline, intracranial response was seen in two of two TKI-naive patients and in three of three TKI-pretreated patients.

“NTRK fusion-positive tumors can present challenges in the clinical setting, which is why it is important that we have additional treatment options for these patients,” TRIDENT-1 global trial lead Alexander Drilon, M.D., from Memorial Sloan Kettering Cancer Center in New York City, said in a statement. “The FDA approval of repotrectinib adds an important tool to our toolbox, offering oncologists a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumors for both TKI-naïve and TKI-pretreated patients.”

Approval of Augtyro was granted to Bristol Myers Squibb.

What are tyrosine kinase inhibitors (TKIs)?

Enzymes called tyrosine kinases act as messengers, relaying signals that govern growth, division, and survival. In cancer, these signals can become corrupted, leading to uncontrolled cell proliferation. Tyrosine kinase inhibitors (TKIs) are a powerful weapon against cancer, precisely targeting these enzymes to disrupt the cancerous growth cycle.

TKIs belong to a class of drugs known as targeted therapies. Unlike traditional chemotherapy drugs that broadly target all rapidly dividing cells, TKIs bind to the active site of tyrosine kinases, mimicking the natural cellular component that would normally activate the enzyme. This competitive binding effectively blocks the transfer of phosphate groups, a crucial step in the signaling cascade that promotes cell growth. With the signal blocked, cancer cells are essentially put on hold, unable to receive the instructions to multiply.

The discovery of the BCR-ABL protein, a fusion protein driving uncontrolled growth in chronic myeloid leukemia (CML), paved the way for the first successful TKI, imatinib. This breakthrough transformed CML from a terminal illness to a chronic manageable condition. The success continues with TKIs targeting various cancers, including non-small cell lung cancer, gastrointestinal stromal tumors, and some types of leukemia.

TKIs offer several advantages over traditional chemotherapy. Their targeted approach minimizes damage to healthy cells, leading to fewer side effects. Additionally, some TKIs can be taken orally, providing a more convenient treatment option for patients. However, resistance can develop over time, as cancer cells mutate to find ways to bypass the TKI blockade. Researchers are constantly working to develop next-generation TKIs to overcome resistance and improve treatment outcomes.

The future of TKIs is bright. As our understanding of the complex signaling networks in cancer evolves, researchers are identifying new targets for even more specific TKIs. Additionally, combining TKIs with other treatment modalities, such as immunotherapy, holds promise for achieving more durable responses.

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