P2, N=300, Recruiting, SOLTI Breast Cancer Research Group

P2, N=42, Recruiting, Gruppo Oncologico del Nord-Ovest

P2, N=100, Recruiting, AstraZeneca

P3, N=710, Recruiting, Daiichi Sankyo

P1, N=165, Recruiting, Iksuda Therapeutics Ltd. | Trial completion date: Sep 2027 --> Dec 2027 | Trial primary completion date: Sep 2026 --> Dec 2026

P3, N=365, Active, not recruiting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Trial primary completion date: Nov 2025 --> Nov 2026

PHERGain-2 shows meaningful HRQoL preservation, expected HP/T-DM1 toxicity, and an outstanding pCR rate comparable with standard chemotherapy plus HP regimens in this patient population.

Mirvetuximab soravtansine (MIRV), which targets folate receptor-1 (FOLR1), is FDA-approved for platinum-resistant tubo-ovarian cancers with ≥75% moderate/strong staining, and emerging studies show meaningful responses to MIRV combination therapy even at lower FOLR1 expression. FOLR1 met current MIRV treatment criteria in one case, while ten others showed expression ranging from 5% to 70%. Although most tumors did not meet current biomarker thresholds for Trastuzumab or MIRV monotherapy, detectable expression supports exploring anti-HER2 T-Dxd and MIRV combination treatments in selected MA/MLA cases.

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.

We present a case of a 66-year-old female with de novo metastatic NSCLC harboring an EGFR mutation, RET rearrangement, and ERBB2 amplification, who experienced transformation to SCLC while on osimertinib. Subsequently, she exhibited primary refractory disease to both first-line platinum doublet with immunotherapy and second-line lurbinectedin...The patient had minimal side effects and obtained a partial response with a progression-free survival (PFS) of 13.1 months, better than historically poor prognosis seen in transformed SCLC. This case underscores the potential role of human epidermal growth factor receptor 2 (HER-2) directed therapies, such as T-DXd, in transformed SCLC.

The relatively higher frequency of respiratory events and the observed differences by monitoring adherence should be interpreted cautiously given the descriptive design. Larger multicenter studies are needed to better define safety patterns and optimal monitoring strategies.

Neoadjuvant RC48 plus camrelizumab and S-1 showed encouraging pathological responses in HER2-overexpressing gastric cancer. The regimen achieved a pCR rate of 25% and an MPR rate of 45.8%. The combination therapy demonstrated a manageable safety profile. Exploratory ctDNA methylation analysis suggested potential for dynamic response monitoring.