NICE Approves Vitrakvi (Larotrectinib): First Histology-Independent Therapy for TRK Fusion-Positive Solid Tumors in England

April 23, 2020 /Bio ValleyBIOON/ -- German pharmaceutical giantBayer(Bayer) Precision oncology drug Vitrakvi (larotrectinib) has recently received positive regulatory news in the UK. The National Institute for Health and Care Excellence (NICE) has issued guidance approving Vitrakvi for use within the UK’s National Health Service (NHS) forTumorPediatric and adult patients with solid tumors harboring neurotrophic receptor tyrosine kinase (NTRK) gene fusions, specifically those who are NTRK gene fusion-positive, have locally advanced or metastatic disease, or for whom surgical resection may result in severe complications, and who have no satisfactory alternative treatment options. Notably, Vitrakvi is the first “tumor-agnostic (histology-independent)” drug made available to NHS patients in the UK through the Cancer Drugs Fund (CDF).

Vitrakvi is a first-in-class oral TRK inhibitor, representing a histology-independent treatment approach., specifically developed forTreatment of tumors harboring NTRK gene fusions, regardless ofTumorOriginating from which part of the body.TRK fusion-driven tumors can occur in various parts of the body and are typically found in rare tumor types, where conventional treatment options (such as surgery, chemotherapy, and radiation therapy) may be unsatisfactory. Vitrakvi demonstrates robust efficacy in pediatric and adult patients with TRK fusion-positive tumors, including those with primary central nervous system (CNS) involvement.Tumorand brain metastases, offering high response rates and durable responses.

Late November 2018,VitrakviObtained the world's first approval in the United States, becomingThe First Oral TRK Inhibitor Ever Approved，It is also the first “tumor-agnostic, broad-spectrum” anticancer drug, ushering in the era of “TumorA New Era of "Tumor-Agnostic" TherapyCurrently, Vitrakvi has been approved in many countries and regions around the world, including the European Union.

The UK NICE decision was based on pooled data from a total of 102 patients, including those from the Phase I study in adult patients, the Phase II NAVIGATE study in adult and pediatric patients, and the Phase I/II SCOUT study in pediatric patients. Of these, 93 patients were from the primary analysis population, and the remaining 9 had primary central nervous system (CNS) tumors.TumorPatients. The results showed that Vitrakvi treatment demonstrated a high response rate, with durable and rapid responses. Specific data: the primary analysis set showed,Overall Response Rate (ORR) was 72%(95% CI: 62, 81), with a complete response (CR) rate of 16% and a partial response (PR) rate of 55%. In another additional analysis that included patients with primary CNS involvement,ORR was 67% (95% CI: 57, 76), with a CR rate of 15% and a PR rate of 51%.

In the primary analysis, the median time to first response for patients treated with Viktarvy was 1.81 months, and the median duration of response had not been reached at the time of analysis (range: 1.6+ to 38.7+ months), with 75% of patients having a duration of response ≥12 months. Among treated patients, 88% (95% CI: 81, 95) were still alive one year after treatment initiation. The median progression-free survival (PFS) had not been reached at the time of analysis. Safety was evaluated in 125 patients with NTRK gene fusions. Most adverse events (AEs) were Grade 1 or 2, and only 3% of patients had to permanently discontinue treatment due to treatment-emergent AEs. Dose reductions were reported in 19 (15%) patients, 10 (8%) of whom had dose reductions due to AEs. Most AEs leading to dose reduction occurred within the first three months of treatment.

Viktarvy for the Treatment of TRK Fusion-Driven Cancers in Adult and Pediatric PatientsClinically Meaningful Improvement in Quality of Life (QoL). In two global, multicenterClinical TrialAmong them, 60% of adult patients reported an improvement in the EORTC QLQ-C30 global health status score. For pediatric patients, 76% reported an improvement in the total PedsQL score.

Amanda Cunnington, Patient Access Lead at Bayer UK, stated: “Bayer welcomes NICE’s recommendation of Viktarvy, as it will provide clinicians in the UK with the first opportunity to offer a treatment targeting the specific disease drivers for adult and pediatric patients with TRK fusion-driven cancers. Bayer is proud to have collaborated with NICE and the National Health Service (NHS) throughout the entire assessment process of this first-in-class therapy, bringing a new potentially beneficial oral treatment option to patients with TRK fusion-driven cancers.”

NTRK gene fusions are abnormal genetic alterations present in a wide range of tumor types, leading to uncontrolled tropomyosin receptor kinase (TRK) signaling and tumor growth. Accumulating evidence indicates that the NTRK genes, which encode TRK proteins, may fuse with other genes, generating signals that can drive cancer growth in multiple sites throughout the body. TRK fusion cancers are overall rare, affecting no more than a few thousand patients annually in Europe. TRK fusions can occur in both children and adults, and across differentTumorOccur with varying frequencies among the types.

The active pharmaceutical ingredient of Vitrakvi is larotrectinib, a potent, oral, selective tropomyosin receptor kinase (TRK) inhibitor designed to directly target TRKs (including TRKA, TRKB, and TRKC), thereby shutting down the signaling pathways that drive tumor growth in TRK fusion cancers. TRK fusion cancers are generally rare, affecting no more than a few thousand patients annually in Europe. The disease can affect both children and adults and occurs with varying frequency across different tumor types. In clinical studies, Vitrakvi was investigated for the treatment of 29 different histological subtypes of solid tumors. Results demonstrated that Vitrakvi exhibits significant and durable antitumor activity against TRK fusion tumors, including primary central nervous system (CNS) tumors and brain metastases, regardless of patient age andTumorHistology. (Bioon.com)

Original Source: NICEapproves oral drug VITRAKVI (larotrectinib), the first histology-independent treatment to be made available in England, for children and adults with TRK fusion driven cancer