Neoadjuvant camrelizumab with chemotherapy (NACI) in PD-L1-negative locally advanced cervical cancer: An open-label, multi-center, single-arm, phase 2 trial.

Abstract

e17510 Background: Locally advanced cervical cancer (LACC) remains associated with suboptimal outcomes with conventional therapies. We previously demonstrated substantial efficacy of neoadjuvant chemo-immunotherapy (NACI) in PD-L1–positive LACC, achieving an objective response rate (ORR) of 97.6%, a pathologic complete response (pCR) rate of 37.6%, and a 3-year event-free survival (EFS) of 95.1% (95% CI, 90.6–99.9), with overall survival (OS) of 96.8% (95% CI, 92.3–100). Emerging evidence suggests immune checkpoint inhibition may also benefit PD-L1–negative disease. This phase II trial evaluated the efficacy and safety of NACI in PD-L1–negative LACC, an underrepresented population with limited treatment options. Methods: This open-label, multicenter, single-arm phase II trial (NCT06288360) enrolled treatment-naïve patients with PD-L1–negative cervical cancer (combined positive score <1), FIGO 2018 stage IB3, IIA2, IIB, or IIIC1r, and tumor size >4 cm. Patients received one cycle of induction chemotherapy with cisplatin plus nab-paclitaxel, followed by two cycles of camrelizumab combined with cisplatin and nab-paclitaxel. Tumor response was assessed per RECIST v1.1, with ORR defined as complete or partial response. Responders underwent radical hysterectomy with pelvic lymphadenectomy, while non-responders received definitive chemoradiotherapy. The primary endpoint was pCR rate; secondary endpoints included ORR, surgical feasibility, safety, and survival. Simon’s two-stage design was applied, with a planned sample size of 40 patients; stage II required at least two responses among the first 14 evaluable patients. Results: Between September 12, 2024 and December 12, 2025, ten patients were enrolled. Nine completed NACI; all achieved an objective response (ORR 100%) and underwent radical hysterectomy, with an R0 resection rate of 100%. Three patients achieved pCR. Among six non-pCR patients, four had no Sedlis-defined intermediate-risk factors and were managed with surveillance. Parametrial invasion (n=1) and lymph node metastasis (n=1) were identified, and both patients received adjuvant chemoradiotherapy. The predefined stage I efficacy criterion was met, enabling progression to stage II. No treatment-related deaths or delays occurred. The most common grade ≥3 immune-related adverse event was lymphocytopenia. Conclusions: Preliminary interim results indicate that neoadjuvant camrelizumab plus chemotherapy shows promising antitumor activity, excellent surgical feasibility, and acceptable safety in PD-L1–negative LACC. While long-term survival and quality-of-life outcomes are pending, these findings support further investigation of chemo-immunotherapy as a neoadjuvant strategy for low-risk LACC regardless of PD-L1 expression status. Clinical trial information: NCT06288360 .