The efficacy and safety of azvudine (FNC) in phase 1 investigator-initiated study in patients with advanced solid tumors.

Abstract

3018 Background: Azvudine has been approved in China for treatment of AIDS and COVID-19. Serial preclinical studies demonstrated remarkable anti-tumor activity, especially in combination with anti-PD-1 therapy. The mechanistic studies have shown that FNC could significantly reduce myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. This ongoing phase 1 investigator-initiated study aims to further confirm the nonclinical findings of FNC in cancer patients. Methods: Patients with advanced solid tumors who had progressed on standard of care (SoC) therapies were eligible in this single-arm, single-center, open-label study with the primary objective of safety and clinical efficacy. All subjects received the SoC of physician’s choice in combination with FNC which was administered orally once daily, with dose escalated across six dose levels: 3mg, 4mg, 5 mg, 6 mg, 7 mg, and 8 mg. Results: As of 31 Oct, 2025, 25 subjects were enrolled, including 22 subjects with pMMR/MSS CRC, 3 subjects with NSCLC. All CRC subjects received the triple-combination regimen of FNC, penpulimab, and fruquintinib. Among the CRC subjects, the total ORR was 18.2%, DCR was 72.7%, the mPFS was 4.3 months (95%CI: 3.32,6.31) and the mOS was 7.6 months (95% CI: 5.09,NR). Four subjects achieved the radiographic response (PR), 2 subjects from the 6 mg dose group, and one subject each from the 5 mg and 7 mg dose groups. A subgroup analysis based on liver metastasis status was performed for the 15 subjects enrolled in the 5 mg, 6 mg, and 7 mg dose groups. The ORR for the 7 subjects without liver metastases was 57.1%, the DCR was 100%, and the mean treatment duration was 33.6 weeks. In contrast, among the 8 subjects with liver metastases, the ORR was 0%, the DCR was 87.5%, and with a mean treatment duration of 16.7 weeks. No DLTs occurred in the 16 evaluable subjects during the DLT observation period. TEAEs were reported in 96.0% of patients, with a TRAE incidence of 36.0%. Most TRAEs were Grade 1/2, including hepatic dysfunction (12.0%), γ-GTP increased (8.0%), weight decreased (4.0%), diarrhoea (4.0%), insomnia (4.0%), and ALP increased (4.0%). One Grade ≥3 TRAE weight decreased occurred in the 3 mg group. SAEs were reported in 24.0% (6/25) of subjects, with only one case of weight decreased in 3 mg group considered possibly related to FNC. Two subjects (8.0%) discontinued treatment due to TEAEs, one of which was abnormal liver function, possibly related to FNC. No treatment related deaths, dose interruptions, or dose reductions were reported. Conclusions: Overall, the combination of FNC with PD-1 and VEGFR inhibitors was safe and well-tolerated, with encouraging clinical activity in advanced/metastatic pMMR/MSS CRC. Clinical trial information: chiCTR2600116125.