Journal of clinical oncology : official journal of the American Society of Clinical Oncology
August 11, 2026 · via Europe PMC
Biomarker-Stratified Phase II Trial of Trastuzumab Rezetecan in Advanced Salivary Gland Carcinoma Across Cohorts With High and Low Human Epidermal Growth Factor Receptor 2 Expression.
Chen GL, Guo Y, Liu X, +17 more, Ji D.
AI summary — for doctors, generated from the abstract only
The HER2 ADC trastuzumab rezetecan achieved a 91.7% response rate in HER2-high and 45.5% in HER2-low advanced salivary gland carcinoma in a phase II trial.
What was studied
A biomarker-stratified phase II trial of SHR-A1811 (4.8 mg/kg every 3 weeks) in 46 patients with unresectable or recurrent/metastatic salivary gland carcinoma (24 HER2-high, 22 HER2-low).
Key findings
- Confirmed ORR 91.7% (including 4 CRs) in HER2-high and 45.5% in HER2-low
- Median PFS and OS not reached in HER2-high; in HER2-low, PFS 12.7 months and OS 21.3 months
- Grade 3 or higher TRAEs in 41.3%, mainly neutropenia (32.6%)
- ILD in 6.5%, all grade 1; no treatment-related deaths
Clinical relevance
This suggests HER2-directed ADCs are highly active in HER2-high salivary cancers and raises the question of benefit in HER2-low disease. The data are from a small single-arm phase II trial.
Who should care
Limitations
Small single-arm phase II with short follow-up in the HER2-low cohort; no randomized comparator.
HER2 testing in advanced salivary gland cancer may open the door to a highly active ADC option.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Purpose
Systemic treatment options for advanced salivary gland carcinoma (SGC) are limited, and prospective data for human epidermal growth factor receptor 2 (HER2)-directed therapy remain sparse, particularly in HER2-low disease. We evaluated trastuzumab rezetecan (SHR-A1811), a HER2-directed antibody-drug conjugate, in prospectively defined HER2-high and HER2-low cohorts.
Patients and methods
In this phase II trial, patients with unresectable locally advanced or recurrent/metastatic SGC were enrolled in separate HER2-high (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) and HER2-low (IHC 1+ or IHC 2+/ISH-) cohorts. Each cohort was independently evaluated using Simon's optimal two-stage design. SHR-A1811 was administered intravenously once every 3 weeks at a recommended starting dose of 4.8 mg/kg. The primary end point was confirmed objective response rate (ORR) per RECIST version 1.1.
Results
Forty-six patients were enrolled and treated, including 24 in the HER2-high cohort and 22 in the HER2-low cohort. The median follow-up was 21.9 months (95% CI, 16.9 to 26.9) and 11.3 months (95% CI, 6.9 to 15.7), respectively. The confirmed ORR was 91.7% (95% CI, 73.0 to 99.0), including four complete responses, in the HER2-high cohort and 45.5% (95% CI, 24.4 to 67.8) in the HER2-low cohort. Median progression-free survival (PFS) and overall survival (OS) were not reached in the HER2-high cohort. In the HER2-low cohort, the median PFS was 12.7 months and the median OS was 21.3 months. Grade 3 or higher treatment-related adverse events occurred in 41.3% of patients, most commonly neutrophil count decreased (32.6%). Interstitial lung disease occurred in 6.5% of patients, all grade 1. No treatment-related deaths occurred.
Conclusion
SHR-A1811 showed high antitumor activity in HER2-high SGC and promising activity in HER2-low SGC, with a manageable safety profile.
DOI
10.1200/jco-26-00671
PMID
42579830
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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