HER-2 exon 20 insertion

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.

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.

Following isolation by prep-HPLC, 1D and 2D NMR studies and HRMS characterization assigned the isolate as Mobocertinib-N-oxide. In addition, NMR-based reaction monitoring was conducted to trace its formation, allowing a plausible mechanism of formation to be proposed.

The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd)...Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events...The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.

P1, N=160, Active, not recruiting, ArriVent BioPharma, Inc. | Trial completion date: Dec 2025 --> Dec 2026

P1, N=200, Recruiting, Nuvalent Inc. | N=150 --> 200 | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Jan 2027

P2, N=93, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Feb 2026; <75% participation

P2, N=61, Not yet recruiting, Guangdong Association of Clinical Trials

P1, N=48, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P2, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

This case shows that perioperative treatment with T-DXd could induce tumor regression and sustain remission, while MRD monitoring enables early detection of molecular progression. These findings emphasize the potential of combining T-DXd and MRD monitoring to tailor treatment to improve outcomes in HER2-mutant NSCLC.

P1/2, N=251, Recruiting, Pierre Fabre Medicament | N=185 --> 251 | Trial completion date: Jun 2028 --> Dec 2029 | Trial primary completion date: Jun 2027 --> Dec 2029