NDA Submission Announcement
On May 26, 2020, Bayer announced the submission of a New Drug Application (NDA) to the Japanese Ministry of Health, Labour and Welfare (MHLW) for Vitrakvi (larotrectinib), a precision oncology medicine. The application seeks approval for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring NTRK gene fusions.
Clinical Data Supporting the NDA
The NDA in Japan is based on pooled data from 102 patients across three clinical trials:
Phase I trial in adult patients
Phase II NAVIGATE trial in adult and adolescent patients
Phase I/II SCOUT trial in pediatric patients
These trials evaluated Vitrakvi in over 20 distinct histologic solid tumor types, including lung cancer, thyroid cancer, melanoma, gastrointestinal stromal tumor, colon cancer, cholangiocarcinoma, soft tissue sarcoma, salivary gland cancer, and infantile fibrosarcoma.
Study Population
93 patients in the primary analysis population
9 additional patients with primary central nervous system (CNS) tumors
Efficacy Results
Primary Analysis Set (n=93)
Overall Response Rate (ORR): 72% (95% CI: 62–81)
Complete Response (CR): 16%
Partial Response (PR): 55%
Extended Analysis (including primary CNS tumors, n=102)
ORR: 67% (95% CI: 57–76)
CR: 15%
PR: 51%
Response Durability and Survival
Median time to first response: 1.81 months
Median Duration of Response (DOR): not yet reached (range: 1.6+ to 38.7+ months)
75% of patients had DOR ≥ 12 months
1-year overall survival rate: 88% (95% CI: 81–95)
Median Progression-Free Survival (PFS): not yet reached
Safety Profile (n=125)
Most adverse events (AEs) were Grade 1 or 2
Only 3% of patients discontinued treatment permanently due to AEs
19 patients (15%) required dose reduction, with 10 (8%) due to AEs
Most dose-reducing AEs occurred within the first 3 months of treatment
Quality of Life (QoL) Outcomes
Vitrakvi demonstrated clinically meaningful improvements in QoL for adults and children:
60% of adult patients reported improved EORTC QLQ-C30 global health scores
76% of pediatric patients reported improved PedsQL total scores
About Vitrakvi (larotrectinib)
Vitrakvi is a first-in-class oral TRK inhibitor. Its active ingredient, larotrectinib, is a potent, highly selective inhibitor of tropomyosin receptor kinases (TRKA, TRKB, TRKC). It directly targets TRK proteins to shut down the oncogenic signaling pathways driving TRK fusion-positive tumors, which can arise in any part of the body and are often refractory to standard treatments (surgery, chemotherapy, radiotherapy).
Global Approval History
November 2018: First global approval in the U.S. as the first oral TRK inhibitor and the first tissue-agnostic ("tumor-agnostic") anticancer drug, regardless of tumor type.
Currently approved in multiple countries and regions, including the European Union.
