L-glutamine combined with chemotherapy produced a 44% response rate in a Phase 1 trial involving patients with advanced pancreatic cancer.

Study reports responses in advanced pancreatic cancer

The GlutaPanc trial evaluated oral L-glutamine in combination with gemcitabine and nab-paclitaxel in 16 patients with advanced pancreatic ductal adenocarcinoma (PDAC), including 15 patients with metastatic disease.

The study, published in Nature Cancer, found that seven of the 16 patients achieved an objective response, giving an overall response rate of 44%. Two patients had complete responses and five had partial responses.

Tumour shrinkage was observed in 15 of the 16 patients, while median overall survival was 22 months and median progression-free survival was 8.5 months.

The researchers said the findings support further investigation of L-glutamine in pancreatic cancer, although the small, single-arm Phase 1 study was not designed to establish whether the combination is more effective than chemotherapy alone.

L-glutamine investigated alongside chemotherapy

The treatment combined L-glutamine with gemcitabine and nab-paclitaxel, a chemotherapy regimen used to treat pancreatic cancer.

L-glutamine is an amino acid involved in several metabolic processes in the body. The researchers investigated whether modifying glutamine availability could affect tumour metabolism and the response to chemotherapy.

The study also examined biological changes associated with treatment, including alterations in intermediary metabolism, the gut microbiome and inflammatory responses.

These findings may help explain how L-glutamine could influence the tumour environment and response to treatment, although the researchers said further studies are needed to establish the underlying mechanisms.

Willis Lee, chairman and CEO of Emmaus Life Sciences, said: “We are incredibly proud to explore the broader potential of our therapies.”

Further clinical development planned

Following the GlutaPanc results, Emmaus Life Sciences has entered an exclusive option agreement with Cedars-Sinai to continue investigating the clinical use of oral L-glutamine in combination with chemotherapy for PDAC.

The agreement allows further development of the approach, but L-glutamine has not been established as a treatment for pancreatic cancer.

The GlutaPanc study was a single-arm Phase 1 trial, meaning there was no control group receiving chemotherapy alone. The researchers therefore cautioned that the results cannot demonstrate that adding L-glutamine improves outcomes compared with standard chemotherapy.

The study’s survival findings were compared with historical data rather than a concurrent control group, further limiting the conclusions that can be drawn from the results.

The researchers concluded that the findings provide a rationale for testing the combination in a randomised controlled trial, which would allow its clinical benefit to be assessed more rigorously.

Emmaus already markets pharmaceutical-grade L-glutamine for sickle cell disease, but its safety and efficacy for pancreatic cancer have not been established and the company has not received regulatory approval for this use.