Penpulimab plus anlotinib as first-line treatment for persistent, recurrent, or metastatic cervical cancer: A multicentre, single-arm, phase II trial.

211 Background: Currently, the established first-line therapy for patients with recurrent or metastatic CC is the platinum-paclitaxel plus bevacizumab, yet chemotherapy-associated toxicity remains a concern. Although the addition of immune checkpoint inhibitors (ICIs) to chemotherapy improves survival, it adds cumulative toxicities and limited tolerability. This phase II trial evaluated the efficacy and safety of a chemotherapy-free regimen—penpulimab (anti-PD-1) plus anlotinib (multi-target TKI)—as first-line therapy in patients with persistent, recurrent, or metastatic CC. Methods: This multicenter, single-arm, phase II trial enrolled women (aged 18-75 years, ECOG PS 0-1) with histologically confirmed persistent, recurrent, or metastatic cervical cancer who had progressed after ≥1 platinum-based regimen and were ineligible for curative local therapy. Prior immunotherapy or antiangiogenic therapy was excluded. Treatment consisted of penpulimab (200 mg IV, day 1) plus anlotinib (12 mg orally, days 1-14) in 21-day cycles until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: From April 2022 to December 2023, twenty-five patients were enrolled (median age 54 years; 52% stage III at diagnosis; 72% PD-L1 CPS ≥1). With a median follow-up of 19.6 months, ORR was 56% (95% confidence interval CI, 35-76), including 5 complete and 9 partial responses; DCR was 88% (95% CI, 69-98). Median PFS was 14.8 months (95% CI, 4.8–not estimated NE); median OS was 25.4 months (20.1-NE). The 12-month OS rate was 88.0% (95% CI, 67.3–96.0). All patients (100%) experienced at least one treatment-related adverse event (TRAE) of any grade. Grade ≥3 TRAEs occurred in 14 patients (56%), with hypertension (12%) being the most common. No treatment-related deaths occurred, and quality of life remained stable throughout the treatment period. Conclusions: Penpulimab plus anlotinib, as a first-line chemotherapy-free regimen, demonstrated promising clinical activity and a manageable safety profile in patients with persistent, recurrent, or metastatic cervical cancer, supporting its further development as a novel treatment option. Clinical trial information: ChiCTR2100053109.