January 22 2020
*Currently Enrolling Patients*
Anti PD-L1 (Atezolizumab) as an Immune Primer and Concurrently with Extended Field Chemoradiotherapy for Women with Node Positive Locally Advanced Cervical Cancer
Cervical cancer accounts for approximately 266,000 deaths globally each year and patients diagnosed with locally-advanced cervical cancer have a higher risk of recurrence and worse survival than early stage patients. Additionally, patients presenting with para-aortic lymph node (PALN) metastases represent a poor prognostic group with only a 5-year survival of approximately 40% across the stages. The NRG Oncology clinical trial NRG-GY017 was designed to address the need for a therapeutic treatment option for this patient population.
Building on the proof of concept in GOG 9929 that immunotherapy can safely be integrated into primary therapy for node positive cervical cancer patients undergoing chemoradiation, NRG Oncology’s clinical trial NRG-GY017 will be observing the anti PD-L1, atezolizumab, as an immune system activation for women with node-positive, locally advanced cervical cancer. Women on this trial will receive atezolizumab either before and/or concurrent with the standard of care chemoradiotherapy. This trial is currently accruing patients with stage IB2, II, IIIB, or IVA cervical cancer that has metastasized to the lymph nodes.
Women who participate on NRG-GY017 will be randomly assigned to one of two potential treatment arms. Participants on Treatment Arm 1 will receive atezolizumab then, if there is no disease progression or unacceptable toxicity, patients will begin to receive concurrent atezolizumab, cisplatin chemotherapy, and the standard of care radiotherapy with image-guided brachytherapy.Participants on Treatment Arm 2 will receive concurrent atezolizumab, cisplatin chemotherapy, and standard of care radiotherapy.
The primary goal of NRG-GY017 is to determine whether the difference in sequencing for the addition of atezolizumab to chemoradiotherapy results in differential immune activation for trial participants. Differential immune activation will be determined by clonal expansion of T cell receptor beta repertoires in peripheral blood on day 21 of treatment.
Other objectives include: investigating the feasibility of administrating atezolizumab as an immune primer and concurrent with chemoradiotherapy, the nature and degree of toxicity from atezolziumab prior and concurrent with chemoradiotherapy, changes in the T cell receptor clonality, diversity, and frequency in peripheral blood and tissue and the correlation of these changes to clinical outcomes, and lastly the predictive value of baseline and PD-L1 expression in tissue in each treatment arms for clinical outcomes. Exploratory objectives are to explore biomarkers that could predict a response to the combination therapy and to explore the response of assessment on the exploratory and optional post-treatment PET-CT scan, and the clinical 2-year disease free survival.
“This trial is of paramount importance to understand the optimal sequencing and underlying immune mechanism when immunotherapy is added to the standard of care chemoradiation in locally advanced cervical cancer,” mentioned the trial’s Study Chairs, Jyoti Mayadev, MD, of the University of California, San Diego and Russell Schilder, MD, of Thomas Jefferson University, and Dmitiry Zamarin, MD, PhD, of Memorial Sloan Kettering Cancer Center.
More information:
ClinicalTrials.gov: NCT03738228
Protocol Documents on CTSU: NRG-GY017