A phase I/Ib trial conducted by the National Cancer Institute’s National Clinical Trials Network group NRG Oncology, NRG-GY017, concluded that the addition of the immunotherapy atezolizumab prior to and concurrently given with chemoradiation was safe for women with node-positive, locally advanced cervical cancer. Trial data also showed that the combination of atezolizumab with chemoradiation exhibited immune-modulating activity. These findings were presented during the Plenary Session of the Society for Gynecologic Oncology’s (SGO) 2022 Annual Meeting on Women’s Cancer.
“The goal of NRG-GY017 was to investigate peripheral blood T-cell receptor (TCR) clonal expansion in response to chemoradiation and immunotherapy, and to establish the safety and efficacy of atezolizumab immunotherapy as a primer to [chemoradiation] combined with atezolizumab. This trial gives insight into the immunological basis for therapy response. These results allow future research to consider immunotherapy and treatment sequencing in larger-scale trials as a way of improving outcomes for this high-risk population of women,” stated Jyoti Mayadev, MD, of the University of California, San Diego, and the lead author of the NRG-GY017 abstract.
NRG-GY017
NRG-GY017 analyzed 36 eligible patients and randomly assigned them to either Treatment Arm A, where patients received three doses of atezolizumab (one prior to chemoradiation, and two doses during chemoradiation); or to Treatment Arm B, where patients received all three doses of atezolizumab during chemoradiation. Tumor biopsies were taken before and during treatment, peripheral blood was collected, and dose-limiting toxicities were assessed for all eligible trial participants. In addition to safety and immunogenicity, researchers were also evaluating secondary objectives including toxicity and the predictive value of T-cell repertoire parameters for clinical outcomes.
The median follow-up for 36 patients was 20 months, and 75% of patients completed all of the study treatment. On the study, 30 patients were evaluable for dose-limiting toxicities: none of the 16 patients on Treatment Arm A exhibited dose-limiting toxicities, and 3 of the 14 patients on Treatment Arm B reported experiencing a dose-limiting toxicity (8%). Overall, 3 patients on Arm Treatment A and 10 patients on Treatment Arm B experienced a grade 3 or higher treatment-related adverse event, with only one being immune-related. There was an increase in peripheral blood TCR clonal expansion and expansion of tumor-associated T-cell clones between the start of treatment and day 21 of chemoradiation in Arm A (P = .0001) and Arm B (P = .001). Patients with higher pretreatment TCR diversity had increased likelihood of complete pathologic response in on-treatment biopsy (P = .049).
Correlations between treatment schedule, T-cell repertoire parameters, and clinical outcomes will be reported at a later date as more data is collected in follow-up.
Disclosure: This project was supported by U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) grants from the National Cancer Institute, part of National Institutes of Health, as well as by Genentech.
