HER-2 mutation

P3, N=400, Recruiting, Boehringer Ingelheim

Three such agents have gained accelerated US Food and Drug Administration (FDA) approval for use in previously treated HER2-mutant NSCLC: the antibody-drug conjugate, trastuzumab deruxtecan; the HER2-specific tyrosine kinase inhibitor (TKI), zongertinib; and the HER2/EGFR TKI, sevabertinib. Zongertinib has also been granted accelerated FDA approval in a first-line setting. The emergence of multiple treatment options highlights the importance of early HER2 mutation testing to guide treatment sequencing and maximize patient benefit.

The second case involves a patient with metastatic micropapillary urothelial carcinoma with HER2 expression, refractory to platinum chemotherapy, avelumab maintenance, and enfortumab vedotin. These two observations illustrate the capacity of T-DXd to induce deep and complete metabolic remissions in distinct HER2-altered solid tumors. They support further development of HER2-targeted ADCs beyond traditional indications and highlight the value of FDG-PET/CT for assessing the depth of response to these agents.

GGOs exhibit a distinct genomic and PD-L1 profile with significant age-related heterogeneity, providing insights for age-stratified therapeutic strategies.

This study demonstrates that SS is distinguished from PCAECTCL not by increased mutational burden but by distinct pathway-level architectures, particularly involving epigenetic regulation, immune signaling, and transcriptional control. These findings generate biologically grounded, testable hypotheses for subtype-specific therapeutic targeting and underscore the value of conversational AI as a scalable framework for accelerating discovery in translational cancer genomics.

P1, N=76, Recruiting, Daiichi Sankyo | N=25 --> 76

She enrolled in a clinical trial of the selective HER2 tyrosine kinase inhibitor zongertinib (60 mg twice daily) in February 2025 and tolerated therapy well, with mild diarrhea, lactose intolerance, brittle nails, and intermittent muscle cramps...As of January 2026, she has maintained lung-confined disease control for over 11 months without extrapulmonary progression and remains fully functional without symptoms. This case highlights the clinical benefit and tolerability of selective HER2-targeted therapy in HER2-mutant NSCLC and adds to emerging evidence supporting consideration of risk-based lung cancer screening strategies in high-risk never-smoking populations.

Our findings demonstrate that "ERBB2-altered cancer" is not a homogenous entity. Optimizing precision oncology for ERBB2 requires integrating histological context, specific alteration types, and co-mutation profiles to guide therapeutic selection and overcome resistance.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

In vivo studies demonstrated pronounced tumor growth inhibition by A9-DA1 in HER2+ xenograft and P6-DA1 in EGFR+ KRAS mutated colorectal and pancreatic xenograft models. Overall, our findings suggest that Ahx-DA1 is a highly effective auristatin-class payload for the development of DA1 based anticancer PDCs.

Specific genetic mutations are associated with survival, response rate, and time to progression after Y-90 radioembolization. This study underscores the potential use of genetic profiling to individualize treatment plans.

P4, N=535, Recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital