HER-2 mutation

P1/2, N=90, Recruiting, Canwell Biotech Limited | Not yet recruiting --> Recruiting

Although HER2-targeted therapies, such as trastuzumab deruxtecan, have shown promising results in HER2-positive bladder cancer, optimal immunohistochemistry (IHC) scoring criteria for urothelial carcinoma remain unclear...Upper GI and breast scoring criteria yield divergent scores in a significant subset of urothelial carcinomas, potentially affecting eligibility for targeted therapy. Associations with histologic subtype and metastatic site support disease-specific diagnostic and therapeutic strategies.

P1/2, N=400, Recruiting, Bayer | Trial primary completion date: Nov 2026 --> Mar 2026

Functional analysis demonstrated increased sensitivity of AZACL2 cells to the BRAF inhibitor dabrafenib and MEK inhibitors including trametinib, compared with BRAF wild-type cell lines. The mutation spectrum was broadly consistent with previous reports, suggesting a conserved molecular landscape across geographic regions. Collectively, these data identify BRAF and HER2 alterations as clinically relevant candidates for molecular diagnostics and targeted therapy in canine pulmonary adenocarcinoma.

Circulating tumor DNA mutation status may serve as a prognostic biomarker in patients receiving HER2-targeted therapies. PIK3CA mutations were associated with worse outcomes, whereas ERBB2 mutations showed no significant effect. The prognostic significance of ctDNA was most pronounced in patients treated with TKIs, particularly pyrotinib, and remained evident in monotherapy and capecitabine-based regimens. These findings support the potential utility of ctDNA monitoring for risk stratification and personalized management in advanced HER2-positive breast cancer.

Rare actionable genomic alterations are recurrently identified in NGS-assessed NSCLC cohorts. These findings support the clinical value of broad genomic profiling, provide realistic expectations for diagnostic yield in routine practice, and may inform precision oncology implementation, molecular-testing pathways, and resource allocation.

P1/2, N=90, Not yet recruiting, Canwell Biotech Limited

NSCLC patients with oncogenic TKD HER2 mutations had different characteristics and genetic features than patients with non-TKD mutations. Real-world outcomes with first- and second-line standard-of-care treatment were suboptimal, highlighting the need for new treatment options for patients with advanced HER2-mutant NSCLC.

The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.

Performing molecular testing (in the absence of adequate tumor tissue with liquid biopsy) as early as possible is already an integral part of the treatment pathway planning for CCA patients. Early molecular testing may therefore lead to the possibility of administering targeted therapy in the first-line setting within this patient group, pending the outcomes of clinical trials.

Therapeutic progress in this population has accelerated over the past several years, first with trastuzumab deruxtecan and more recently with selective HER2 tyrosine kinase inhibitors (TKIs). Zongertinib demonstrates that selective HER2 inhibition can achieve durable responses in HER2 -mutant NSCLC with a favorable safety profile. However, optimal treatment sequencing, resistance mechanisms, and biomarker-guided patient selection remain to be defined.

p53 IHC, particularly using a ≥40% cut-off at 3+ intensity, is an accurate and accessible surrogate for TP53 mutation detection in LUAD patients. This method facilitates rapid molecular stratification, optimal resource utilization and informed prognostic and therapeutic decision-making in routine pathology practice.