Triage of advanced cervical cancer through immunotherapy induction (TRACTION).

TPS5622 Background: In advanced/recurrent cervical cancer, immune checkpoint inhibitors have emerged as an attractive alternative and have demonstrated impressive therapeutic responses. As a result, the combination of pembrolizumab with platinum/taxane chemotherapy with or without bevacizumab received FDA approval for first-line systemic therapy in persistent, recurrent, or metastatic PD-L1+ cervical cancer. However, this regimen demonstrates the greatest impact on survival when all four drugs are utilized and are not without the potential for significant toxicity. CheckMate-358 utilized two dosing regimens of ipilimumab and nivolumab in advanced/recurrent cervical cancer. In the preliminary results, the utilization of either dosing regimen resulted in remarkable, durable responses in chemo-naïve patients with the median overall survival not reached. Given the potential benefit of CTLA-4/PD-1 blockade in the upfront setting, we propose a phase II trial examining the strategy of induction immunotherapy with lorigerlimab (bispecific antibody targeting CTLA-4 and PD-1) in chemo-naïve cervical cancer patients not amenable to curative treatment. Methods: The study is a phase II, multi-site clinical trial conducted at MD Anderson Cancer Center and Lyndon B. Johnson General Hospital. In the induction phase, patients will receive intravenous (IV) lorigerlimab at the recommended phase II dose (6 mg/kg) for three 21-day cycles with a repeat CT scan performed at week 9 of treatment. Tumor response (by RECIST v1.1) to induction immunotherapy will be used to triage patients to either continuation of lorigerlimab (if at least stable disease) or standard of care treatment (if disease progression) in the triaged treatment phase. Lorigerlimab will be continued until progression or intolerable toxicity, for a maximum of 35 cycles. At any time point, all patients at first disease progression will subsequently receive physician’s choice standard of care systemic therapy with carboplatin/paclitaxel +/- pembrolizumab +/- bevacizumab and will be followed for survival. The primary objective is to estimate disease control rate. Secondary objectives are to determine objective response rate, duration of response, overall survival, progression-free survival, and safety (by CTCAE v5.0). Key eligibility criteria include 1) recurrent, metastatic, or persistent cervical cancer 2) squamous cell carcinoma, adenosquamous, or adenocarcinoma histologic subtype 3) not amenable to curative surgery or radiation. The trial is open with 14 of planned 40 patients enrolled at the time of submission. Clinical trial information: NCT05475171 .