NTRK fusion

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

The Pan Lung Cancer PCR Panel was highly concordant with other assays. The panel can be performed in local laboratories with a rapid turnaround time and represents an attractive alternative to next-generation sequencing for patients with lung cancer.

Owing to the presence of neural tissue, NTRKs are highly positive in IHC, making these genes unsuitable as biomarkers for assessing NTRK inhibitor sensitivity and resistance, which are tissue-agnostic drugs. The observed low fusion rate is consistent with the literature, and the significance of the numerous point mutations identified as agnostic markers warrants further investigation. NTRK expression, fusion, and point mutations were not associated with clinical parameters or survival.

While first-generation TRK kinase inhibitors, such as entrectinib and larotrectinib, have shown positive responses in TRK fusion-positive cancers, resistance mutations against these inhibitors in the kinase domain limit their efficacy...By conjugating entrectinib to thalidomide, we identified JWJ-01-378 as a potent and selective cereblon (CRBN)-recruiting degrader of the TPM3-TRKA fusion...TPM3-TRKA degradation by JWJ-01-378 suppressed downstream signaling and reduced cancer cell viability, with improved responses compared to a heterobifunctional control compound that cannot degrade TPM3-TRKA. Together, our study expands the toolbox of selective compounds for evaluating targeted degradation of TRK fusions in diseases including cancer.

While these practices have become more commonplace, unified guidelines have yet to be established. In this review of the literature, we evaluate the advantages and pitfalls of sequential biomarker testing during disease progression in patients with mCRC.

P2, N=60, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

These studies demonstrate that NTRK wild-type receptors are important drivers of brain metastatic colonization and progression in different subtypes of lung cancer, independent of their driver alterations. Thus, they provide rationale to expand the use of FDA-approved NTRK inhibitors with brain penetrance for the prevention of CNS metastases.

NTRK-fusion defines a distinct PTC molecular subtype characterized by a high burden of LNM and a spectrum of features linked to follicular growth patterns. These findings facilitate the preoperative identification of this tumor subtype and provide a foundation for individualized risk stratification and tailored management strategies.

P2, N=60, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris

Somatic PGVs in potentially targetable pathways were found in 72% of ATC tumors. Given the aggressiveness of ATC and the limited efficacy of current treatments, these findings support the rationale for biomarker-driven basket trials investigating the efficacy of targeted therapies in this population.

Multiple rare thyroid malignancies may present indistinguishably from ATC, emphasizing the need for meticulous histopathologic and molecular evaluation.

There are several challenges including the lack of randomized perioperative trials, heterogeneity in pathological response assessment, and uncertainty regarding the reliability of surrogate endpoints. With the increasing integration of next-generation sequencing into the standard diagnostic workup of early-stage NSCLC, biomarker-directed perioperative strategies supported by prospective clinical trials enriched for specific genotypes are critical to achieving sustained clinical outcomes in these patient subgroups with rare targetable alterations.