289MO - Fruquintinib plus sintilimab in advanced cervical cancer (CC) patients (pts): Results from a multicenter, single-arm phase II study

Background

Fruquintinib (F, a highly selective VEGFR inhibitor) plus sintilimab (S, an anti-PD-1 monoclonal antibody) showed promising antitumor activity in both pre-clinical and clinical studies. Here, we reported the results of F plus S from CC cohort in an open-label, multicenter, single-arm phase 2 study.

Methods

Pts with pathologically confirmed advanced CC who had failed at least first-line platinum-containing treatment, or experienced intolerable toxicity during treatment, or were unable to receive standard therapy were eligible. Eligible pts received F (5 mg, 2 weeks [wk] on/1 wk off, orally, once daily) plus S (200 mg, IV, every 3 wk) in 21-day cycles, until disease progression or unacceptable toxicity. Treatment of S was allowed for up to 24 months (mo). The primary endpoint was ORR per RECIST v1.1.

Results

As of May 30, 2023, 34 pts were successfully enrolled and received F plus S, median follow-up duration was 16.4 mo. Median (range) age was 56 (26.2, 73.7) yrs. 6 pts (17.6%) were treatment naïve (naïve pts); 28 pts (82.4%) had received at least first-line treatment (treated pts), including bevacizumab (5/28), for advanced disease. 25 pts (73.5%) had received pelvic radiation therapy. There were 24 pts (70.6%) with PD-L1 status of CPS ≥1. Among tumor evaluable naïve and treated pts, confirmed ORR (cORR) were 50.0% (PR 3/6) and 29.6% (CR 1/27 and PR 7/27); median TTR were 2.7 and 3.1 mo; DCR were both 100%. In naïve (N=6) and treated (N=28) pts, mPFS were 10.3 and 8.2 mo, 15mo-OS rate were 83.3% and 70.0%. In tumor evaluable treated pts stratified by CPS ≥1 vs <1 (N= 17 vs 8), cORR was 41.2% vs 12.5%; in treated pts (N=18 vs 8), mPFS was 19.4 vs 5.2 mo; mOS was not reached vs 13.9 mo, 15mo-OS rate was 76.0% vs 50.0%. All pts experienced TEAEs, and the most common TEAEs included proteinuria (64.7%), hypothyroidism (61.8%), asthenia (44.1%), hyperthyroidism (44.1%), palmar-plantar erythrodysaesthesia syndrome (44.1%), anaemia (41.2%) and urinary tract infection (41.2%).

Conclusions

F plus S provided favorable efficacy in advanced CC pts, especially for treated PD-L1 CPS ≥1 pts. This combination treatment also showed manageable toxicity profile consistent with that seen in other cohorts.

Clinical trial identification

NCT03903705.

Editorial acknowledgement

Legal entity responsible for the study

HUTCHMED Limited.

Funding

HUTCHMED Limited.

Disclosure

All authors have declared no conflicts of interest.