HER-2 amplification

P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed

Together with prior preclinical and clinical evidence, these findings support a context-dependent model in which target downregulation predominates in HER2-low disease, whereas payload resistance or rare binding-site mutations may dominate resistance in HER2-addicted tumors, with important implications for antibody-drug conjugate selection and sequencing. See related article by Chen et al., p. 235.

Both HER2 IHC positive (3+) and FISH positive occur exclusively in pure USC tumors. HER2 gene amplification can be observed in any HER2 IHC levels.

P3, N=246, Active, not recruiting, R-Pharm

Despite some significantly different clinicopathological features, there is no solid evidence to support HER2-ultralow, HER2-low and HER2-null cancers as individual TNBC clinical-molecular entities. Particularly, assigning TNBC samples to the HER2-null, -ultralow and -low categories did not bring any additional prognostic value.

In addition, PD-1 blockade does not rescue the hematopoietic damage caused by TNBC, highlighting a limitation in long-term response. Furthermore, PD-1 blockade in tumor-free mice leads to an increase in hematopoietic stem/progenitor cells, suggesting that PD-1 blockade may yield better benefits post-tumor resection.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.

P1, N=280, Recruiting, SystImmune Inc. | Trial completion date: Aug 2027 --> Apr 2029 | Trial primary completion date: Dec 2025 --> Dec 2028

Furthermore, conditioned media from the treated BC cells induced the proliferation of PMA treated monocyte like THP-1 cells and provoked the secretion of IL-6, while reducing IL-10. These findings suggest that the CD151-LEL-based peptides and their engineered multiepitope construct represent a prospective vaccine candidate for in vivo experimental validation, which can be used as a therapeutic vaccine for breast cancer.

P1, N=48, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026