ERBB3 positive

P1, N=42, Not yet recruiting, Actinium Pharmaceuticals Australia Pty Limited

TK-hu A3 emerged as the lead candidate, showing specific HER3 targeting, strong pathway inhibition, and antitumor efficacy in vivo. Beyond standalone use, it could support novel strategies such as T-cell engagers, ADCs, CAR-T, and bispecific antibodies. These findings highlight TK-hu A3 as a promising therapy for HER3-positive, treatment-resistant cancers, meriting further development.

HER3 expression may serve as a critical biomarker for guiding therapeutic strategies in HER2-positive breast cancer patients. The combinatorial effect of HER3 overexpression and PIK3CA mutations may exacerbate therapeutic resistance, while dual-targeted strategies against the HER3/PI3K pathway could potentially improve clinical outcomes in treatment-resistant populations.

Our findings also suggest that evaluating the response of SBAs to anti-HER3 therapies should be considered in future clinical trials. Additionally, evidence of spatial heterogeneity in biomarker expression emphasizes the importance of assessing biomarkers in metastatic tissue to identify actionable alterations that may not be present in the primary tumor.

It was found that the new affiprobe allowed the detection of HER3 expressing cells with a detection limit of 14578 cells per 200 μl assay volume and a working range of 14000 to 50000 cells. The new affiprobe can be used for detecting, studying and monitoring the HER3-expressing cells using a luminometer in fast and inexpensive assays.

Claudin 18.2, nectin-4, and HER3 are potential therapeutic targets in SBA, and nectin-4 positivity is independently associated with an unfavorable prognosis. These proteins may represent new therapeutic targets for SBA.

This multifaceted approach could ultimately lead to more personalized treatment options for patients with HER3-positive breast cancers, thereby improving overall patient management and outcomes in this challenging disease landscape. This study presents recombinant affibodies tailored to bind to HER3 for cancer cell identification, along with novel methods for producing a range of affibody molecules.

These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.

Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.

P1/2, N=184, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2023

HMBD-001 will next be evaluated in Part B in biomarker selected mCRPC with Enzalutamide. Trials of HMBD-001 in squamous NSCLC and NRG1 fusions are also planned for Q3/4 2023.

P1/2, N=184, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial completion date: Dec 2023 --> Dec 2024