Vitrakvi (larotrectinib) / Bayer, Pfizer - LARVOL DELTA

Congenital mesoblastic nephroma: a single-center retrospective study. (PubMed, Transl Pediatr) - "Two relapsed patients received salvage chemotherapy [vincristine-actinomycin D-cyclophosphamide (VAC) or ifosfamide-carboplatin-etoposide (ICE)], which showed limited efficacy. One relapsed patient with TPM3::NTRK1 received larotrectinib but died two months later; another with EGFR-KDD experienced disease stabilization after afatinib plus programmed cell death protein 1 (PD-1) blockade following progression on entrectinib and anlotinib...While most patients experienced favorable outcomes following surgery, relapsed cases highlight the challenges associated with molecularly atypical disease. These observations are descriptive in nature and underscore the need for larger collaborative studies to better define prognostic factors and optimal management strategies in CMN."

IO biomarker • Journal • Retrospective data • Kidney Cancer • Oncology • Pediatrics • Renal Cell Carcinoma • Solid Tumor • EGFR • ETV6 • NTRK1 • NTRK3 • TPM3

Efficacy and safety of larotrectinib as first-line treatment for patients with TRK fusion cancer. (PubMed, ESMO Open) - P1, P1/2, P2 | "Larotrectinib achieved extremely durable responses, extended survival and had a favourable safety profile in treatment-naïve patients with TRK fusion cancers, supporting its use in this population. Elective discontinuation of larotrectinib may be feasible in selected paediatric patients, with response achievable after restarting larotrectinib in cases of recurrent off-therapy disease."

Journal • Endocrine Cancer • Fibrosarcoma • Oncology • Pediatrics • Salivary Gland Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Thyroid Gland Carcinoma

Larotrectinib (L) in patients (pts) with solid tumors with NTRK1/2/3 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Oncology • Solid Tumor • NTRK1 • NTRK2 • NTRK3

Comprehensive Analysis of Adult NTRK-Rearranged Sarcomas: Clinical, Pathologic, and Genomic Correlates (USCAP 2026) - "Only 9 of 19 patients received a TRK inhibitor; larotrectinib time on treatment (median: 12.5 months) was suggestive of response... Adult NTRK-rearranged sarcomas are exceedingly rare, displaying wide anatomic distribution, morphologic diversity, and frequent high-grade presentation. While TRK inhibitors demonstrate activity across fusion types, concurrent genomic alterations and advanced stage at diagnosis may adversely affect outcomes. Recognition of their histologic spectrum and molecular confirmation remain essential for accurate classification and therapeutic decision-making."

Clinical • Fibrosarcoma • Sarcoma • Solid Tumor • Spindle Cell Sarcoma • CDK4 • EML4 • MDM2 • NF1 • NTRK • NTRK1 • NTRK2 • NTRK3 • RB1 • STRN • TERT

Efficacy and safety of larotrectinib as first-line treatment for patients with TRK fusion cancer (Sarcoma-RC 2026) - P1, P1/2, P2 | "Legal entity responsible for the study Bayer HealthCare Pharmaceuticals, Inc. Funding These studies were funded by Bayer HealthCare Pharmaceuticals, Inc."

Clinical • CNS Tumor • Fibrosarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NTRK

Vitrakvi: Expiry of patents related to active ingredients in China, Brazil and US in 2029 (Bayer AG) - Annual Report 2025: Expiry of patents related to active ingredients in Canada in 2031, Germany, France, Italy, Japan and Spain in 2034 and Switzerland in 2035

Patent • Appendix Cancer • Colorectal Cancer • Fibrosarcoma • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Salivary Gland Cancer • Soft Tissue Sarcoma • Solid Tumor • Thoracic Cancer • Thyroid Gland Carcinoma

Larotrectinib for NTRK Amplification in Glioblastoma: Case Report (AAN 2026) - " A 51-year-old man with multifocal, MGMT-unmethylated glioblastoma underwent resection followed by chemoradiation with temozolomide, six cycles of adjuvant temozolomide, and tumor treating fields...Third-line lomustine and bevacizumab were subsequently initiated... In patients with glioblastoma with NTRK amplification, this case suggests limited benefit with treatment with Larotrectinib as compared to previously demonstrated significant efficacy in NTRK fusion–positive gliomas. These findings highlight the necessary requirements to distinguish between NTRK fusions and amplifications when clinically considering targeted TRK inhibition. This case reports bridges the importance of molecular profiling to guide therapy selection."

Case report • Clinical • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • MGMT • NTRK • NTRK2

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Bayer | Trial completion date: Dec 2019 ➔ Sep 2020 | Trial primary completion date: Jun 2019 ➔ Sep 2020

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov) - P2 | N=176 | Recruiting | Sponsor: Loxo Oncology, Inc. | Trial primary completion date: Apr 2018 ➔ Dec 2019

Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • NTRK1 • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Bayer | N=104 ➔ 174

Enrollment change • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=155 | Recruiting | Sponsor: Bayer | Trial primary completion date: Jul 2026 ➔ Jun 2025

Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

Three novel concomitant NTRK2 fusions in medullary thyroid carcinoma with diagnostic implications. (PubMed, Discov Oncol) - "Tumors harboring these fusions respond dramatically to TRK inhibitors (e.g., larotrectinib, entrectinib, and repotrectinib), which selectively target the constitutively active fusion protein. Conclusively, this first report of three novel NTRK2 fusion transcript variants co-occurrence in an MTC patient expands the known spectrum of translocation partners in NTRK2 rearrangements. Prospective validation of their impact on TRK-targeted therapy efficacy and disease prognosis requires long-term follow-up."

Journal • Oncology • Pediatrics • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: Loxo Oncology, Inc. | Trial primary completion date: Jun 2017 ➔ Jun 2019

Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Bayer | Trial primary completion date: Aug 2023 ➔ Jul 2025

Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NTRK1 • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Bayer | Trial completion date: Sep 2024 ➔ Aug 2027 | Trial primary completion date: Sep 2024 ➔ Aug 2027

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: Loxo Oncology, Inc. | Phase classification: P1 ➔ P1/2 | N=36 ➔ 84

Enrollment change • Phase classification • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Bayer | N=200 ➔ 120 | Trial completion date: Oct 2026 ➔ Sep 2025 | Trial primary completion date: Oct 2026 ➔ Sep 2025

Enrollment change • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NTRK1 • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=154 | Active, not recruiting | Sponsor: Bayer | Trial primary completion date: Jan 2026 ➔ Jul 2024

Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

Corticosteroids for Managing TRK Inhibitor Withdrawal Pain: A Report on Two Cases. (PubMed, Curr Oncol) - "Inhibitors such as larotrectinib, entrectinib and repotrectinib are used when cancer cells harbor NTRK1, NTRK2 or NTRK3 fusion...Short courses of prednisone for the former and dexamethasone for the latter were initiated after failure of standard analgesia... For patients experiencing TRK inhibitor withdrawal pain, especially when tapering down the inhibitor is not an available strategy, a short course of corticosteroids can provide lasting relief. These cases emphasize the importance of better understanding the mechanism underlying the relationship between NRTK, NGF and nociception."

Journal • Oncology • Pain • Solid Tumor • NTRK • NTRK1 • NTRK2 • NTRK3

Discovery of a Novel Phenyl Thiophene-3-carboxamide Derivative DZX19 as an Orally TRK Inhibitor with Potent Antitumor Effects. (PubMed, J Med Chem) - "However, the clinically approved TRK inhibitors, including Larotrectinib and Entrectinib, are limited by insufficient efficacy and resistance due to kinase mutations. In the Km-12 xenograft model, DZX19 significantly suppressed tumor growth. These results indicate that DZX19 serves as a novel TRK-targeting lead compound for further investigation."

Journal • Oncology • NTRK • NTRK1 • TPM3

NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov) - P2 | N=203 | Recruiting | Sponsor: Bayer | N=120 ➔ 203

Enrollment change • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • NTRK1 • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1/2 | N=155 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jul 2025 ➔ Jul 2024

Enrollment closed • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3

Adjuvant Larotrectinib in a Resected Secretory Carcinoma-Like Lung Adenocarcinoma Harboring EML4-NTRK3 Fusion: Case Report. (PubMed, JTO Clin Res Rep) - "After adjuvant chemotherapy, maintenance larotrectinib was initiated based on proven TRK inhibitor efficacy in metastatic NTRK-fusion tumors and emerging evidence for targeted therapy benefit in driver-positive early stage lung adenocarcinoma. Our findings demonstrate the value of molecular pathology in the diagnostic journey of pulmonary malignancies, guiding rare fusion detection and supporting therapeutic decisions based on rare fusions in early stage disease."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Salivary Gland Cancer • Solid Tumor • EML4 • NTRK • NTRK3

NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: Bayer | N=176 ➔ 320 | Trial completion date: Dec 2019 ➔ May 2021 | Trial primary completion date: Dec 2019 ➔ May 2021

Enrollment change • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • NTRK1 • NTRK2 • NTRK3

SCOUT: A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Loxo Oncology, Inc.

New P1 trial • Brain Cancer • Breast Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • ETV6 • NTRK • NTRK3