P1, N=25, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Dec 2023 --> Jan 2025

P2, N=73, Completed, SOLTI Breast Cancer Research Group | Active, not recruiting --> Completed

P1/2, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Phase classification: P1b --> P1/2 | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.

P2, N=257, Completed, Palleos Healthcare GmbH | Active, not recruiting --> Completed

P1, N=16, Completed, Shanghai Pharmaceuticals Holding Co., Ltd

P2, N=55, Recruiting, SOLTI Breast Cancer Research Group | Trial primary completion date: Dec 2023 --> Dec 2024

The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2 imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer. Keywords Breast cancer ; HER2 ;Trastuzumab ;T2 imaging properties; Near infrared fluorescence imaging; Early detection .

However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

Our strategy proved effective in reconstructing the complex signalling network driving EGFR-targeted therapy resistance, offering new insights for the development of individualized treatment strategies in TNBC.

P3, N=900, Active, not recruiting, Shanghai Henlius Biotech | Recruiting --> Active, not recruiting

After intraventricular administration in rats, we demonstrated that the brain-to-blood efflux of Fab was up to 10 times lower than for trastuzumab, associated with a two-fold higher brain penetration compared to trastuzumab. This Fab, capable of significantly reducing brain-to-blood efflux and enhancing brain penetration after intra-cerebrospinal fluid injection, could thus be a new and original effective drug in the treatment of HER2 breast cancer brain metastases, which will be demonstrated by a phase I clinical trial dedicated to women in resort situations.

In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. This study is a retrospective study, which does not require clinical registration.

P3, N=688, Recruiting, Henan Cancer Hospital | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

P=N/A, N=58, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2024 | Trial primary completion date: Nov 2024 --> Mar 2024

P1, N=537, Active, not recruiting, Genentech, Inc. | Trial completion date: Apr 2024 --> May 2025 | Trial primary completion date: Apr 2024 --> May 2025 | Recruiting --> Active, not recruiting

The combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.

P1, N=15, Not yet recruiting, Bayer

P1, N=48, Active, not recruiting, Carisma Therapeutics Inc | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2023 --> Dec 2024

P1/2, N=14, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=47 --> 14

This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

P3, N=4804, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2028 --> Nov 2024

P1, N=8, Completed, Bayer | Active, not recruiting --> Completed

P=N/A, N=194, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025

P3, N=27, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=300 --> 27 | Trial completion date: Sep 2026 --> Nov 2024 | Trial primary completion date: Jun 2026 --> Nov 2024

We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.

P1, N=48, Completed, Peking University | Active, not recruiting --> Completed

Baseline sHER2 ECD levels and its early decline may be useful biomarkers for SOX plus trastuzumab efficacy in HER2 positive gastric cancer.

In our study, a third of patients with stage II-III hormone receptor-negative and HER2-positive breast cancer had a complete pathological response after only three cycles of neoadjuvant systemic therapy. A complete response on breast MRI could help identify early complete responders in patients who had hormone receptor negative tumours. An imaging-based strategy might limit the duration of chemotherapy in these patients, reduce side-effects, and maintain quality of life if confirmed by the analysis of the 3-year event-free survival primary endpoint. Better monitoring tools are needed for patients with hormone receptor-positive and HER2-positive breast cancer.

P2; These results highlight the clinical, biological, and metabolic heterogeneity of HER2+ breast cancer, which may facilitate the selection of HER2+ EBC patients likely to benefit from [18F]FDG-PET imaging as a tool to guide therapy.

Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC.

In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs.

Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC)...The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure...In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.

Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients.

Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy.

Our results suggest that UniCAR T cells guided with soluble linkers present a viable alternative to conventional CAR T cells, especially for patients resistant to antibody therapy and those with solid tumors exhibiting high antigenic variability. Critical to their success, however, is the choice of an appropriate binding domain for the CAR and the corresponding soluble linker, ensuring both efficacy and safety in therapeutic applications.

Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.

The knockdown of PSMC1 and PSMD11 in LUAD cells increased their sensitivity to afatinib and decreased cell migration, invasion and proliferation. In addition, the cells showed significantly lower EGFR expression, indicating that PSMC1 and PSMD11 may mediate therapeutic sensitivity through EGFR expression.

177Lu-DOTAGA-Fab and trastuzumab are suitable for targeting the HER2 receptors.

P2, N=3, Completed, German Cancer Research Center | Active, not recruiting --> Completed | N=60 --> 3 | Trial completion date: Dec 2024 --> Oct 2023 | Trial primary completion date: Dec 2024 --> Oct 2023