April 12 2023
Written by NRG-HN010 Principal Investigator, Alan Ho, MD
Salivary gland cancers (SGCs) are rare tumors that constitute ~5% of head and neck malignancies, representing >20 different histologic types. These orphan diseases are understudied and lack effective systemic therapy options. One of the most promising therapeutic targets for SGCs is the overexpression and/or amplification of the Her2/neu gene (“Her2+”). Over a third of salivary duct carcinomas are Her2+, as well as lesser percentages of adenocarcinomas, ex-pleomorphic carcinomas, mucoepidermoid carcinomas and other histologies. Two single-arm phase II trials which combined enrolled 100 Her2+ SGC patients in Asia (Japan and South Korea) observed that the combination of docetaxel and the Her2-directed antibody trastuzumab can produce a high rate of response (67-70%) and progression-free survival of ~8-9 months. This is now considered the most widely accepted standard therapy for this situation. Smaller prospective cohorts have also demonstrated intriguing signals of activity with other Her2-directed antibodies and Her2 antibody-drug conjugates. Among the most promising agents is ado-trastuzumab-emtansine (T-DM1), an ADC consisting of the Her2 antibody trastuzumab conjugated via a non-cleavable linker to the cytotoxic, antimitotic agent DM1. In a very small 10 patient Her2+ SGC cohort, T-DM1 produced a metabolic or structural response in 9 (90%) patients, including those previously treated with Her2-directed drugs.
In collaboration with NCI-CTEP and Genentech, NRG-HN010 has been developed to be a first-of-its kind, randomized phase II trial comparing the first-line efficacy of docetaxel plus trastuzumab and T-DM1. The outcomes of this trial will establish the new standard of care for Her2+ SGC tumors. The study will enroll patients with unresectable or recurrent/metastatic SGCs that possess Her2 overexpression/amplification determined by local or commercial assays (i.e., immunohistochemistry, fluorescent in-situ hybridization, or next-generation sequencing). 116 eligible patients will be randomized 1:1 to one of the Her2-directed regimens with the primary objective of comparing PFS between the two arms, predicting that T-DM1 will produce superior disease control over docetaxel plus trastuzumab. Cross-over to the alternate treatment arm is allowed at time of progression. Secondary objectives include evaluating overall response rate, overall survival, and patient reported toxicities. Exploratory objectives include investigating molecular biomarkers associated with treatment susceptibility and resistance, as well as evaluating the efficacy of cross-over treatment at time of progression.
Any NCTN site may participate and activate this trial via CTSU. For any questions regarding this study, please contact the principal investigator, Dr. Alan L. Ho (email@example.com).