HER-2 positive + HER-2 overexpression

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Jun 2026 --> Jul 2027

She received first-line chemotherapy with trastuzumab, pertuzumab, and docetaxel, followed by maintenance anti-HER2 therapy and surgery for local disease control. This case may represent an exceptional response to T-DM1 and highlights the potential for durable complete remission in selected patients with HER2-positive metastatic breast cancer. Further investigation is warranted to identify predictive factors for exceptional responses and to determine optimal treatment duration.

Secondary endpoints include duration of response, progression-free survival, disease control, occurrence of treatment-emergent adverse events, and health-related quality of life. Recruitment is ongoing in 13 countries globally.Clinical trial registration http://www.clinicaltrials.gov identifier is NCT06581432.

Notably, RC48 retained strong activity in BT474-derived sublines resistant to T-DM1, lapatinib, or neratinib, inducing cell cycle arrest, apoptosis, and caspase activation in all resistant models. Together, these findings identify disitamab vedotin as a potent next-generation HER2-targeting ADC with the unique capacity to overcome acquired resistance to HER2-directed therapies. RC48 represents a promising therapeutic strategy for patients with refractory HER2-positive breast cancer and warrants further clinical investigation.

Peripheral blood ALC levels are negatively correlated with HER2 expression in breast cancer. Given its accessibility and cost-effectiveness, ALC may serve as a complementary systemic immune indicator for contextual assessment of HER2-related immune characteristics and immune heterogeneity at the population level.

P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026

HER2-low HR+ RecurIndex-DR low risk patients may not benefit from adjuvant chemotherapy. RecurIndex may help explore prognostic stratification and may guide potential chemotherapy de-escalation in HER2-low early BC, laying groundwork for future ADC use.

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2026 --> Jul 2030 | Trial primary completion date: Dec 2026 --> Jun 2026

P=N/A, N=1050, Recruiting, Institut Claudius Regaud | Not yet recruiting --> Recruiting

The patient was started on capecitabine and oxaliplatin in addition to trastuzumab with subsequent clinical and radiological improvement. Unresectable, metastatic HER2 positive conventional adenocarcinoma is being managed using platinum-fluoropyrimidine doublet therapy with anti-HER2 monoclonal antibody trastuzumab. This case report calls for aggressive IHC staining for prompt diagnosis where necessary as well as proper guidelines for management.

Unexpectedly, dual-ligand AaLS protein nanoparticles (AaLS/TRAIL/A10 and AaLS/TRAIL/2Rb17C) exhibited biphasic cytotoxicity; low doses synergistically enhanced apoptosis in HER2-positive cells, whereas higher doses reduced efficacy, likely due to the activation of survival signaling. These results highlight the importance of dose optimization for maximizing the use of TRAIL-based targeted therapies.

These findings establish avisomes as a highly promising theranostic platform for HER2-positive breast cancer. Its genetically encoded, self-assembling nature eliminates the major limitations of ADCs and synthetic nanoparticles, providing a scalable, reproducible, and cost-efficient alternative for next-generation targeted cancer therapy.