A novel combination therapy pairing a DNA-synthesis inhibitor with a targeted radiopharmaceutical may improve outcomes for patients with advanced neuroendocrine tumours, according to new clinical trial data presented this week at the European Society for Medical Oncology (ESMO) Congress 2025.

Aman Chauhan, M.D., leader of the Neuroendocrine Tumour Programme at Sylvester Comprehensive Cancer Centre, part of the University of Miami Miller School of Medicine, and associate professor of medical oncology at the Miller School, presented findings from a National Cancer Institute (NCI)-sponsored phase 1 clinical trial.

The study results investigate the combination of a ribonucleotide reductase inhibitor (RRI) with lutetium Lu 177 dotatate, a targeted radiopharmaceutical therapy, in patients with progressive, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Neuroendocrine tumours are rare cancers and have relatively limited treatment options. Lutetium Lu 177 dotatate, a radiolabeled somatostatin analogue, has become a standard treatment for somatostatin receptor-positive GEP-NETs. However, many patients eventually experience disease progression.

According to a National Institutes of Health study, the incidence and prevalence of neuroendocrine tumours have continued to increase.

In fact, the data indicate that the number of people diagnosed with NETs has almost doubled over the last two decades.

Deaths from these tumours have also increased, though survival has improved for many patients.

Chauhan’s recent research explores whether adding an RRI to lutetium Lu 177 dotatate can improve treatment outcomes.

The RRI inhibits ribonucleotide reductase, an enzyme essential for DNA synthesis and repair.

This mechanism may sensitise tumour cells to radiation, potentially enhancing the effectiveness of lutetium Lu 177 dotatate.

“Neuroendocrine tumours are complex and often overlooked, but advances in research and treatment are giving us new ways to improve survival and quality of life for patients. Our goal is to bring greater awareness to these rare cancers and offer every patient the most precise and personalised care possible,” Chauhan said.

“This combination represents a novel strategy to overcome treatment resistance in GEP-NETs.”

The phase 1 trial, conducted under the NCI-funded Experimental Therapeutics Clinical Trials Network (ETCTN), enrolled patients with progressive, well-differentiated GEP-NETs. The primary objectives were to assess safety, tolerability and early signs of efficacy.

The results have led to a phase 2 randomised trial, which recently completed patient enrollment at 14 sites across the United States.

The phase 2 study compares the RRI plus lutetium Lu 177 dotatate to lutetium Lu 177 dotatate alone, aiming to determine whether the combination improves progression-free survival.

Chauhan’s research emphasises theranostics—integrating diagnostics and therapeutics—to personalise cancer treatment.

He has led multiple clinical trials involving radiopharmaceuticals, targeted therapies and novel drug combinations.

If successful, the RRI and lutetium Lu 177 dotatate combination could reshape the treatment landscape for GEP-NETs, Chauhan said.

It may offer a new therapeutic option for patients who have exhausted standard treatments and inspire further research into combination strategies involving radiopharmaceuticals and DNA synthesis inhibitors.

NCI 10388 and NCI 10558 are also supported by Nanopharmaceutics LLC through Cooperative Research and Development Agreements with NCI.

The presentation will be delivered during the mini oral session on neuroendocrine and endocrine tumours, Oct. 20, and is titled “Multi-centre NCI-sponsored phase 1 study of Triapine in combination with 177 Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs).”

Source: University of Miami Miller School of Medicine