A phase II study of anlotinib plus penpulimab as first-line treatment for persistent, recurrent, or metastatic cervical cancer: Results from ALTER-GO-020 trial.

5527 Background: In patients with recurrent, or metastatic cervical cancer, atezolizumab combined with bevacizumab and chemotherapy has significantly enhanced progression-free survival (PFS) and overall survival (OS) regardless of PD-L1 status. ALTER-GO-020 trial was designed to evaluate the efficacy and tolerability of anlotinib (a multitarget anti-angiogenic TKI) and penpulimab (anti-PD-1 antibody) as a chemotherapy-free regimen for patients (pts) with recurrent or metastatic gynecological cancer. This report presents the latest efficacy and safety data from the completed cervical cancer cohort. Methods: ALTER-GO-020 is a single arm, open-label, multi-cohort, multi-center phase II clinical study. In cervical cancer cohort, 26 pts were planned to be enrolled. Eligible pts were histologically confirmed persistent, recurrent, or metastatic cervical cancer (including adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma), not amenable to curative treatment, and had no prior systemic treatment for metastatic, persistent, or recurrent disease. Pts were treated with anlotinib (12mg, po qd, d1-14, q3w) plus penpulimab (200mg, IV, d1, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included PFS, duration of response (DOR), disease control rate (DCR), OS and safety. Results: 26 pts were enrolled. The median age was 52 years (range, 31-70), 65% of pts were squamous-cell carcinoma, 88% received previous chemoradiotherapy with or without surgery, and 71% had previously received neoadjuvant/adjuvant platinum-containing chemotherapy. As of date cutoff (Dec, 2024), the median follow-up time was 11.7 months (range, 1.3-30.0 months). In the efficacy analysis (n=26), the preliminary ORR was 50% (95% CI: 32.1%-67.9%), DCR was 92.3% (95% CI: 75.9%-98.6%). The mPFS was 11.0 months (95% CI: 5.8m-16.2m months). The mOS was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in all 26 pts, in which 12 (46.2%) were grade ≥3. The most common grade ≥3 TRAEs were hypertension (19.2%), hand foot syndrome (11.5%), fatigue (3.8%), and diarrhea (3.8%). TRAEs led to dose reduction and interruption were 15.4%, and 38.5% of pts, respectively. No TRAEs leading to death. Conclusions: Anlotinib combined with penpulimab as a chemotherapy-free regimen showed a significant improvement in ORR, a trend towards longer PFS, and favorable safety in the treatment of pts with recurrent or metastatic cervical cancer. Clinical trial information: NCT05028504 .