Neoadjuvant chemo-immunotherapy following concurrent immuno-chemoradiotherapy and immune-maintenance therapy as primary treatment for locally advanced cervical cancer: A prospective, single-arm, phase 2 trial.

5533 Background: Immunotherapy in combination with chemoradiotherapy has shown good efficacy in locally advanced cervical cancer (LACC). We report on the efficacy of neoadjuvant camrelizumab plus chemotherapy (TP) following concurrent immuno-chemoradiotherapy and maintenance immunotherapy for LACC. Methods: Eligible participants were adults with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2018 stage IIB-IVA disease), ECOG PS score 0-2, and adequate bone marrow and organ function. All pts received 2 cycles neoadjuvant camrelizumab (200 mg d1 q3w) plus TP (albumin-bound Paclitaxel 260mg/m 2 d1 q3w; cisplatin 75 mg/m 2 d1-3 q3w) treatment, following 5-week external beam radiotherapy (EBRT) protocol (45-50 Gy/25 fractions with concurrent triweekly camrelizumab and cisplatin) to the whole pelvis plus brachytherapy every 3 weeks for 2 cycles, and then maintenance therapy of camrelizumab (200mg q3w, up to one year). The primary endpoint was progression-free survival (PFS) at 2 years. PFS was evaluated when at least 13 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.05. Results: 67 pts provided informed consent and 12 were excluded for not meeting eligibility. 55 pts received the investigational agent and were evaluable for safety and efficacy analyses. The median age was 54 years IQR 50 to 60; 51 92.7% were squamous cell carcinoma, and 4 7.3% were adenocarcinoma; 9 16.4% were stage IIB, 2 3.6% were IIIA, 5 9.1% were IIIB, 30 54.5% were IIIC1r, 6 10.9% were IIIC2r, and 3 5.5% were IVA. As of data cutoff (Jan. 15, 2024), median follow-up was 9.5 (IQR 7.1 to 10.3) months. Of the 55 pts, 1 (1.8%) pt underwent hysterectomy after EBRT because of pelvic empyema, and was excluded from response evaluation. At three months after brachytherapy, the overall remission rate was 100% (53 98.1% complete remission and 1 1.9% partial remission). We identified 3 (5.5%) pts with treatment failure (2 3.6 distant metastasis, and 1 (1.8% para-aortic lymph node relapse) during follow-up; 1-year PFS was 90.6% (85.4%-95.8%). The most common clinically significant grade 3-4 adverse events (AEs) were decreased neutrophils (18.2%), thrombocytopenia (9.1%) and anemia (27.3%). Serious AEs occurred in 7 (12.7%), most commonly due to infectious complications. There were no treatment-related deaths. Conclusions: The interim data support Camrelizumab plus TP neoadjuvant chemo-immunotherapy following immuno-chemoradiotherapy and Camrelizumab maintenance therapy as an active go-forward regimen in LACC. No new safety signals were observed, and most AEs were mild to moderate. Clinical trial information: ChiCTR2200061097.