Namodenoson Surpasses Halfway Enrollment Benchmark in Advanced Pancreatic Cancer Trial

Over 50% of the intended population of patients with advanced pancreatic adenocarcinoma whose disease has progressed after 1 or more prior lines of therapy have been enrolled in a phase 2a trial (NCT06387342) evaluating the efficacy and safety of the A3 adenosine receptor (A3AR) agonist namodenoson.1,2

“This milestone reflects the strong interest among both investigators and patients in exploring namodenoson as a potential treatment for one of the deadliest and most aggressive cancers,” Pnina Fishman, PhD, chief scientific officer of Can-Fite BioPharma, stated in a news release.1 “We are encouraged by the pace of enrollment and remain committed to advancing namodenoson as a much-needed therapeutic option for patients with pancreatic cancer.”

Namodenoson is a small, highly selective and orally bioavailable drug that was developed to bind strongly to A3AR on the surface of liver and pancreatic cancer cells.3 The agent works by de-regulating the NF-κB and Wnt signal transduction pathways, triggering apoptosis of these malignant cells.4

With low expression of A3AR on normal cells, namodenoson also has a favorable safety profile.3 

Notably, preclinical studies have demonstrated that namodenoson exhibits significant anti-proliferative activity against BxPC-3 pancreatic cancer cells.1,5,6 In vitro exposure of these cells to namodenoson at doses ranging from 5 nM to 20 nM for 24 hours resulted in dose-dependent growth inhibition, which was reversed by the A3AR antagonist MRS1523.5 Western blot analyses revealed modulation of NF-κB, as well as modulation of proteins in the RAS and Wnt/β-catenin signaling pathways, with upregulation of the apoptotic markers Bad and Bax. Furthermore, in vivo, mice treated with namodenoson at 10 µg/kg twice daily for 35 days had significantly reduced tumor growth compared with control mice.

A separate in vitro study showed that namodenoson at doses ranging from 0.01 nM to 1 nM significantly inhibited cell proliferation in a dose-dependent manner (P < .005).6 Additionally, combining namodenoson with gemcitabine had an additive inhibitory effect (P < .001). Further analysis confirmed downregulation of key Wnt pathway proteins. These findings support the further evaluation of namodenoson as a potential therapeutic agent in pancreatic cancer.

Additionally, on October 9, 2024, the FDA granted orphan drug designation to the agent in pancreatic cancer.3

The multicenter, open-label study is enrolling approximately 20 patients 18 years of age or older with histologically or cytologically confirmed pancreatic adenocarcinoma, or disease that was clinically diagnosed based on scan results and a serum cancer antigen 19-9 value greater than 1000 U/mL on at least 1 occasion.2 The disease must be refractory to treatment or metastatic, and patients must have previously received no standard therapies that would be given with curative intent. Prior therapy must be discontinued at least 14 days prior to the baseline visit.

Notably, patients with a history of treated central nervous system (CNS) metastases can enroll if there is disease outside the CNS; there is no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study; and there is no history of intracranial hemorrhage or spinal cord hemorrhage.

Eligible patients will receive namodenoson in oral capsules at a dose of 25 mg twice daily in continuous 28-day cycles.

The primary end points are the type, incidence, severity, and seriousness of adverse effects and their relationship to namodenoson in addition to ECOG performance status changes from baseline. Secondary end points include typical efficacy parameters, such as objective response rate, progression-free survival, disease control rate, duration of response, and overall survival.

Investigators will also explore quality of life, pharmacokinetics, and changes in baseline cancer antigen 19-9 levels and carcinoembryonic antigen levels.

References

1. Pancreatic cancer phase 2a study with Can-Fite’s namodenoson achieved over 50% enrollment milestone. News release. Can-Fite. July 30, 2025. Accessed July 30, 2025. https://ir.canfite.com/news-events/press-releases/detail/1091/pancreatic-cancer-phase-2a-study-with-can-fites
2. Namodenoson treatment of advanced pancreatic cancer. ClinicalTrials.gov. Updated January 31, 2025. Accessed July 30, 2025. https://www.clinicaltrials.gov/study/NCT06387342?term=NAMODENOSON&rank=1
3. FDA grants orphan drug designation to CanFite’s namodenoson for pancreatic cancer. News release. CanFite. October 9, 2024. Accessed July 30, 2025. https://ir.canfite.com/news-events/press-releases/detail/1068/fda-grants-orphan-drug-designation-to-can-fites
4. Namodenoson (CF102). CanFite. 2021. Accessed July 30, 2025. https://www.canfite.com/category/Namodenoson
5. Itzhak I, Bareket-Samish A, Fishman P. Namodenoson inhibits the growth of pancreatic carcinoma via deregulation of the Wnt/β-catenin, NF-κB, and RAS signaling pathways. Biomolecules. 2023;13(11):1584. doi:10.3390/biom13111584
6. Fishman P, Bareket-Samish A, Itzhak I. Effects of namodenoson on pancreatic carcinoma: preclinical evidence. J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.e15134