Bayer's Tumor-Agnostic Cancer Drug Vitrakvi Receives Positive CHMP Opinion for NTRK Fusion-Positive Solid Tumors in Europe

July 29, 2019 /Bio ValleyBIOON/ -- German pharmaceutical giantBayer(Bayer) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the targeted anticancer drug Vitrakvi (larotrectinib) 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.

The CHMP’s assessment opinion will now be submitted to the European Commission (EC), which will take the CHMP’s opinion into account and issue a final review decision within the next 2–3 months. Vitrakvi is a first-in-class oral TRK inhibitor specifically developed for the treatment of tumors harboring NTRK gene fusions. If approved, Vitrakvi will become the first therapy approved in Europe “TumorDrugs for "agnostic" indications. Currently, Vitrakvi has been approved in the United States, Brazil, and Canada.

The CHMP’s positive opinion is based on pooled data from a total of 102 patients, comprising 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)TumorPatients. The results demonstrated that treatment with Vitrakvi yielded high, durable, and rapid response rates. Specifically, the primary analysis showed an overall response rate (ORR) of 72% (95% CI: 62, 81), including a complete response (CR) rate of 16% and a partial response (PR) rate of 55%. In an additional analysis that included patients with primary CNS tumors, the ORR was 67% (95% CI: 57, 76), with a CR rate of 15% and a PR rate of 51%. In the pooled primary analysis set, the median duration of response had not been reached at the time of analysis (range: 1.6+ to 38.7+ months), and 75% of patients had a duration of response ≥12 months. Among treated patients, 90% (95% CI: 83, 97) were alive one year after treatment initiation. At the time of analysis, the median progression-free survival (PFS) had not been reached. Safety was evaluated in 125 patients with NTRK gene fusions. Most adverse events (AEs) were Grade 1 or 2; 3% of patients discontinued treatment due to treatment-related AEs. Dose reductions were reported in 19 (15%) patients, 10 (8%) of whom reduced doses due to AEs. Most AEs leading to dose reduction occurred within the first three months of treatment.

NTRK gene fusions are abnormal genetic alterations present in a wide range of tumor types, leading to uncontrolled tropomyosin receptor kinase (TRK) signaling andTumorGrowth. Increasing evidence indicates that the NTRK genes, which encode TRK proteins, may fuse abnormally with other genes, generating signals that can drive cancer growth in multiple sites throughout the body.

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 occur in both children and adults and arises 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 results?

In late November 2018, Vitrakvi was approved by the U.S.FDAApproved for pediatric and adult patients with advanced solid tumors harboring NTRK gene fusions, specifically those without known acquired resistance mutations, with metastatic disease or where surgical resection may result in serious complications, and who have no satisfactory alternative treatment options or have experienced disease progression following treatment.

This approval makes Vitrakvi the first oral TRK inhibitor in history, as well as the first “broad-spectrum” anticancer drug that is tumor-agnostic, ushering in a new era of “TumorA New Era of "Tumor-Agnostic" Therapy. (Bioon.com)

Original Source:Bayer receives positive CHMP opinion for precision oncology treatment larotrectinib with first ever tumor-agnostic indication in in Europe