Researchers published promising clinical data in the Journal for ImmunoTherapy of Cancer (JITC), from two phases I clinical trials using Anti-PD-1 treatment for 124 Chinese recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients. An objective response rate (ORR) of 29.8% and a durable clinical benefit (DCB) rate of 60.5% have been achieved with the median overall survival as 17.1 months. Patients without liver metastasis had a significantly longer overall survival after the treatment.
In this study, the research team from Sun Yat-sen University Cancer Center and Geneseeq Technology Inc. further performed genomic profiling of the pre-treatment tumor tissues of these patients by whole-exome sequencing (WES) aiming to identify biomarkers related to treatment outcomes. Although tumor mutation burden (TMB) is a promising biomarker for immune-oncology (IO) therapies in certain cancer types, it was not for NPC. As a result, NPC-specific molecular biomarkers that can potentially predict treatment response are urgently needed.
Furthermore, the researchers identified the granzyme pathway that has recently been proven to associate with IO therapy outcome in other cancer types, especially GZMB and GZMH. Results showed that patients, who experienced gene copy number loss of GZMB or GZMH, had a significantly lower response rate to the treatment and a lower survival rate compared to the patients without such gene loss. Moreover, the researchers also characterized other key immune-related pathways including gasdermin family and IFN, among which copy number loss in GZMB and GZMH occurred at the highest frequency.
“Knowing the copy number alterations in granzymes sheds light on the long-term survival and the disease’s biomarkers responding to anti-PD-1 treatment in NPC patients.” Says Dr. Hua Bao, author and the Director of Research & Development at Geneseeq. “Moving forward, we would like to prospectively examine such biomarkers for predicting IO therapy outcomes in NPC patients and provide more insights into granzymes’ function during immunotherapy.”