NTRK2 fusion

Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.

P2, N=60, Not yet recruiting, Teligene US | Initiation date: Jan 2024 --> May 2024

After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.

Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion.

One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery...The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.

P2, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

P2, N=146, Recruiting, Genentech, Inc. | N=85 --> 146

P2, N=85, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2024 --> Dec 2025

A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified.

P1/2, N=69, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2023 --> Jun 2025

P2, N=13, Recruiting, Children's Hospital of Philadelphia | Not yet recruiting --> Recruiting

Touch imprint slides provide a reliable alternative, especially when neoplastic cells are scarce in permanent biopsies or decalcification deters nucleic acid quality. Based on our experience, we suggest making touch imprints on a routine basis, especially for every bone biopsy. Once digitally scanned duplicates are made, original slides can be safely used for DNA-/RNA-based molecular studies.

P2, N=215, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting

However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

To the best of our knowledge, we reported the first case demonstrating anti-tumor activity of repotrectinib in a patient with AC carring an ETV6-NTRK3 gene fusion, indicating that repotrectinib may be an efficient therapeutic option for tumors with NTRK gene rearrangements.

P1/2, N=50, Recruiting, Memorial Sloan Kettering Cancer Center

A ROS1-rearranged NSCLC with CNS metastases responded to sequential tyrosine kinase inhibitors treatment of crizotinb followed by entrectinib. This report has potential implications in guiding decisions for the treatment after crizotinib resistance.

A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.

P2, N=13, Not yet recruiting, Children's Hospital of Philadelphia | Initiation date: Nov 2023 --> Feb 2024

Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.

We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.

Our patient is now 1 year from resection without disease progression on larotrectinib. This case highlights the importance of expanded NGS testing, particularly in rare tumors.

These modifications altered the response to TKI treatment both in vitro and in vivo. Overall, these models serve as valuable tools for studying the biology of NTRK fusion tumors, their treatment response in a treatment-naïve or -experienced state, and the mechanisms underlying treatment resistance.

P1/2, N=500, Recruiting, Turning Point Therapeutics, Inc. | Trial completion date: Dec 2024 --> Feb 2028 | Trial primary completion date: Jun 2024 --> Feb 2028

In conclusion, the identification of NTRK2 fusions in patients with soft tissue tumors could significantly improve the clinical outcome through selective NTRK inhibitor therapy, especially in the first-line setting. Prompt RNA-based NGS testing at initial diagnosis may benefit these patients. Our case is among the first few in the literature on NTRK2 fusion sarcoma with first-line larotrectinib therapy in the primary and metastatic setting, with good clinical response and minimal side effects.

Introduction: Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibodydrug conjugate (ADC), is now the standard of care for patients with HER2- positive metastatic breast and gastric/gastroesophageal cancers, and those with ERBB2-mutated metastatic non-small-cell lung cancer (NSCLC)... HER2 expression is not routinely assessed in solid tumors with no approved indications for an anti-HER2 antibody. Many patients will undergo CGP to determine eligibility for approved targeted therapies, where genomic ERBB2 alterations will also be identified. As additional anti-HER2 ADCs emerge, CGP can identify ERBB2 genomic alterations which may be sensitive to these targeted therapies, providing additional opportunities in cancers with limited treatment options.

Here we report a large cohort of NTRK fusions detected in a broad range of tumor types during routine clinical care in the community setting. The number of unique and novel fusion partners identified highlights the value of RNAbased NGS, and demonstrates that when performed along with DNA NGS, provides a comprehensive assessment of NTRK fusions and actionable gene alterations to inform the routine clinical care of cancer patients.

One of these contained a novel fusion involving the NTRK2 and LRRFIP2 genes, while the other showed loss of MSH2 and MSH6 without genetic alterations in the encoding genes suggesting an epigenetic background. Genetic characteristics of ATRX-deficient IDH-wildtype adult high-grade gliomas suggest that these tumors are particularly intriguing targets of potential future therapeutic interventions including immunotherapies combined with MAPK pathway inhibition and DNA repair inhibitors.

Variant-specific PCR was performed for 744 tumors with a normal 5'/3'-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK3 fusions were detected in 2/447 (0.5%) non-lung adult malignancies. In conclusion, this study describes a diagnostic pipeline that can be used as a cost-efficient alternative to conventional methods of NTRK1-3 analysis.

Adjuvant single-agent Doxorubicin had been applied until in September 2020 a CT scan had revealed extensive multifocal recurrent disease. Thus, second line Docetaxel and Gemcitabine had been initiated before rapid progressive disease after two cycles prompted salvage surgery... We report the case of a patient with uterine sarcoma harboring a newly described NTRK3 gene fusion partner IGDCC3 that shows a rapid clinical response to treatment with LARO.

In this larger dataset larotrectinib continued to demonstrate rapid and durable responses, extended survival, and favorable long-term safety in pts with advanced TRK fusion lung cancer, including those with CNS mets. These results support the wider adoption of next-generation sequencing testing for NTRK1–3 gene fusions in pts with lung cancer.

All patients received radiotherapy and temozolomide as first-line therapy...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)... Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.

P1, N=0, Withdrawn, Turning Point Therapeutics, Inc. | N=24 --> 0 | Recruiting --> Withdrawn

P2, N=13, Not yet recruiting, Children's Hospital of Philadelphia | Initiation date: Aug 2023 --> Nov 2023

There were no instances of MSI in 56 non-colorectal tumors carrying ALK, ROS1, RET or NTRK1 rearrangements. An analysis of tyrosine kinase gene translocations is particularly feasible in KRAS/NRAS/BRAF wild-type microsatellite-unstable CRCs, although other categories of tumors with MSI also demonstrate moderate occurrence of these events.

P1/2, N=280, Recruiting, DualityBio Inc. | Not yet recruiting --> Recruiting

For this real-world population of patients with FoundationOneCDx solid tumor profiles in the routine course of clinical care, clinically significant findings were reported for approximately half of patients with genomic results.

Moreover, these results are consistent with the literature data concerning the molecular dichotomy (BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification.

P2, N=60, Not yet recruiting, Teligene US

Clinical testing laboratories may benefit from improved understanding of strengths and limitations of different workflows. It is important to keep these in mind when reporting results.