Neoadjuvant chemoimmunotherapy before chemoradiation vs chemoradiation alone for stage IIB-IIIC1 carcinoma of the cervix: A phase II open-label randomized controlled trial (NeoCHIMERA).

Abstract

TPS5631 Background: Locally advanced cervical cancer (FIGO 2018 stages IIB–IIIC1) remains a major cause of cancer-related mortality in low- and middle-income countries. Concurrent chemoradiation (CCRT) with brachytherapy is the current standard of care; however, rates of persistent disease and distant failure remain substantial, particularly in patients with bulky tumors or nodal involvement. Although advances in radiotherapy have improved outcomes, survival in resource-constrained settings continues to lag behind that in high-income countries. Recent randomised trials have demonstrated improved outcomes with two distinct strategies: delivery of dose-dense induction chemotherapy followed by timely initiation of chemoradiation, and the addition of immunotherapy with pembrolizumab to concurrent chemoradiation followed by maintenance therapy for up to one year. Despite these advances, concerns about radiotherapy dose and technique in induction chemotherapy trials, and the feasibility of prolonged maintenance immunotherapy in resource-limited settings, have limited widespread adoption. The optimal dose, timing, and duration of immunotherapy in locally advanced cervical cancer remain undefined. This study was designed to evaluate whether short-course neoadjuvant chemo-immunotherapy administered prior to standard CCRT can improve early tumor response with an acceptable safety profile while preserving treatment feasibility across diverse healthcare settings. Methods: The NeoCHIMERA trial is a multicenter, open-label, randomized phase II study designed to evaluate this hypothesis. Eligible patients include those with biopsy-proven FIGO 2018 stage IIB–IIIC1 cervical carcinoma (squamous, adeno, or adenosquamous histology) who are treatment-naïve and suitable for CCRT. Participants will be randomized 1:1 to the experimental or control arm, stratified based on stage and histology. The experimental arm will receive six weeks of neoadjuvant carboplatin (AUC 2) and paclitaxel (60 mg/m²) weekly, combined with low-dose nivolumab (40 mg IV every three weeks for two cycles), followed by standard CCRT (cisplatin 40 mg/m² weekly with external beam radiation and brachytherapy). The control arm will receive CCRT alone. The primary endpoint is complete clinical response at 3 months after completion of chemoradiation. Secondary endpoints include safety, treatment completion rates, event-free survival, quality of life, and cost-effectiveness from a societal perspective. A total of 154 patients (77 per arm) will be accrued. One interim safety analysis is planned after 40 patients with predefined stopping rules for excess toxicity. Thirty-three of the planned 154 participants have been recruited. This study is registered with the Clinical Trials Registry of India (CTRI/2025/04/085540). Clinical trial information: CTRI/2025/04/085540.