Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer

<jats:sec><jats:title>Background</jats:title><jats:p>There is a lack of data exploring the use and optimal timing of immunotherapy and chemoradiation therapy (CRT) in node-positive cervical cancer. Further translational research into mechanisms of response and resistance to immunotherapy in advanced cervical cancer is warranted.</jats:p></jats:sec><jats:sec><jats:title>Primary Objective(s)</jats:title><jats:p>To determine if sequencing of atezolizumab and CRT result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peripheral blood on day 21.</jats:p></jats:sec><jats:sec><jats:title>Study Hypothesis</jats:title><jats:p>There is a difference for clonal expansion of T cell receptor beta repertoires in the peripheral blood at day 21 between the priming and concurrent atezolizumab and CRT in Arm A vs the concurrent atezolizumab and CRT in Arm B.</jats:p></jats:sec><jats:sec><jats:title>Trial Design</jats:title><jats:p>Locally advanced cervical cancer patients with lymph node-positive disease will be randomized on this open-label, randomized trial with two experimental arms. Arm A will get one dose of atezolizumab prior to cisplatin CRT, and then two subsequent doses of atezolizumab during the CRT, and Arm B will get three doses during CRT. Patients will be followed for 2 years to assess outcomes.</jats:p></jats:sec><jats:sec><jats:title>Major Inclusion/Exclusion Criteria</jats:title><jats:p>Patients must have histologically confirmed, newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): FIGO 2009 clinical stages IB2/IIA with positive para-aortic nodes, or FIGO 2009 clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes. Exclusion criteria include those who had a prior hysterectomy or lymph node dissection.</jats:p></jats:sec><jats:sec><jats:title>Primary Endpoint(s)</jats:title><jats:p>Clonal expansion of TCRB) repertoires in peripheral blood on day 21.</jats:p></jats:sec><jats:sec><jats:title>Sample Size</jats:title><jats:p>The sample size will be 40 patients.</jats:p></jats:sec><jats:sec><jats:title>Estimated Dates for Completing Accrual and Presenting Results</jats:title><jats:p>We estimate accrual to finish by the summer of 2020 with presentation of results to follow in 2021.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03738228">NCT03738228</jats:ext-link>.</jats:p></jats:sec>