Toripalimab with chemoradiotherapy followed by toripalimab maintenance therapy for newly diagnosed, high-risk, locally advanced cervical cancer (TorCH-CC): A single-arm phase II study.

5520 Background: Despite concurrent chemoradiation (CRT) being the standard treatment, patients with high-risk locally advanced cervical cancer (FIGO 2018 III-IVA, HR-LACC) experience suboptimal survival outcomes. This phase II clinical trial aimed to evaluate the efficacy and safety of toripalimab, an innovative and cost-effective PD-1 inhibitor, combined with CRT and followed by toripalimab maintenance, in patients with HR-LACC. Methods: Patients with untreated HR-LACC were enrolled. All patients were treated with cisplatin-based CRT combined with toripalimab, and followed by toripalimab maintenance therapy. Toripalimab is administered at a fixed dose of 240mg every 3 weeks intravenously, with the concurrent CRT and immunotherapy phase not exceeding 8 weeks. The primary endpoint was 2-year PFS rate, with secondary endpoints including overall response rate (ORR), duration of response (DoR), treatment-related adverse events (TRAEs), immune-related adverse events (iRAEs), 2-year OS, and quality of life. Results: From October 2023 to December 2024, 43 patients were enrolled, with a median age of 52 years (range: 28–72). Most patients (79%) were at stage IIIC, while others were stage IIIB (16.3%) or IVB (with inguinal or supraclavicular lymph node metastasis, 4.7%). PD-L1 expression was CPS <10 in 32.6% and CPS ≥10 in 67.4%. All received VMAT radiotherapy and image-guided high-dose-rate intracavitary/interstitial brachytherapy, with 74.4% receiving 5-6 cycles of concurrent chemotherapy and 90.7% receiving 3 cycles of concurrent toripalimab. The median CRT duration was 52.7 days (range: 43–62), and the median D90 HR-CTV was 93.9 Gy (EQD2, range: 84–114). With a median follow-up of 8 months (range: 3–15 months), the ORR was 97.1% at 3 months post-treatment, with 32 complete and 2 partial responses, and 1 stable disease. The best ORR after CRT was 100%, with 41 complete and 2 partial responses. Grade 3 or 4 hematologic TRAEs occurred in 27.9% of patients, and non-hematologic in 2.3%, with no discontinuations or deaths. Grade 3 or 4 hematologic irAEs occurred in 7% of patients. Conclusions: Toripalimab combined with cisplatin-based CRT followed by toripalimab maintenance was well-tolerable and demonstrated promising antitumor efficacy in patients with HR-LACC. Trial registration: The study was registered at ClinicalTrials.gov, NCT06416696. Clinical trial information: NCT06416696 .