1519P - Fruquintinib plus sintilimab in patients (pts) with either treatment-naïve or previously treated advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: 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 a gastric cancer (GC) cohort in an open-label, multicenter, single-arm phase II study in China.

Methods

Advanced gastric or GEJ adenocarcinoma pts with PD-L1 status of CPS ≥1, who had no prior systemic therapy or had failed at least first-line treatment were enrolled. Eligible pts received F (5 mg, 2 weeks on/1 week off, orally, once daily) plus S (200 mg, IV, every 3 weeks) 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 February 28, 2023, 27 pts were enrolled and received F plus S, including 20 treatment-naive pts (i.e.: 1^st -line pts), and 7 pts with prior treatment (i.e.: ≥ 2nd-line pts). Median (range) age was 63.71 (35.8, 74.6) years. There were 8 (29.6%), 9 (33.3%), and 8 (29.6%) pts with PD-L1 status of 1≤ CPS <5, 5≤ CPS<10, and 10≤ CPS, which was tested by the central lab, respectively. Median duration of treatment of F and S were 6.90 and 7.13 months. Among tumor evaluable pts (N=18 for 1^st -line pts, N=6 for ≥ 2nd-line pts), confirmed ORRs were 72.2% and 33.3% in 1^st -line pts and ≥ 2nd-line pts, respectively; clinical responses correlated with level of PD-L1 status. DCRs were 100% and 83.3% in 1^st -line pts and ≥ 2nd-line pts; median TTR reached 2.7 mo and 2 mo in 1^st -line pts and ≥ 2nd-line pts. 9-month PFS rates were 63.8% and 50.0% in 1^st -line pts and ≥ 2nd-line pts. Median PFS and OS were not mature. Common (≥20%) treatment-related treatment-emergent adverse events included proteinuria (48.1%), hypothyroidism (40.7%), aspartate aminotransferase increased (25.9%), alanine aminotransferase increased (22.2%), hypertension (22.2%), and weight decreased (22.2%).

Conclusions

F plus S provided favourable efficacy and manageable toxicity profile in pts with advanced gastric or GEJ adenocarcinoma, especially for pts who cannot tolerate chemotherapy.

Clinical trial identification

NCT03903705.

Editorial acknowledgement

Editorial support was provided by Haoyun Shi of HUTCHMED Limited.

Legal entity responsible for the study

HUTCHMED Limited.

Funding

HUTCHMED Limited.

Disclosure

P. Lu; H. Shi; P. Tan; S. Fan; M. Shi; W. Su: Financial Interests, Personal, full or part-time employment: HUTCHMED Limited. All other authors have declared no conflicts of interest.