Pancreatic cancer - Emerging treatments

Clinical trials

Many clinical trials are ongoing for all stages of disease. National Cancer Institute: clinical trials Opens in new window Participation in clinical trials is especially encouraged.[1]

Zenocutuzumab

Zenocutuzumab is a bispecific, humanised IgG1 antibody that binds to HER2 and HER3 receptors, preventing interaction with neuregulin 1 (NRG). One phase 1 and 2 trial to assess its efficacy and safety in patients with pancreatic cancer harbouring an NRG1 fusion is in progress.[127] Zenocutuzumab has been granted accelerated approval by the US Food and Drug Administration (FDA) for the treatment of advanced unresectable or metastatic NRG1 fusion-positive pancreatic cancer. It is recommended by the National Comprehensive Cancer Network (NCCN) for the subsequent treatment of locally advanced, metastatic, or recurrent pancreatic adenocarcinoma harbouring NRG1 gene fusion in patients with good or intermediate performance scores in certain circumstances.[1]

Pelareorep

Pelareorep, a wild‐type variant of reovirus, functions by activating the immune system and triggering anti-tumour immune responses. One phase 2 trial evaluating pelareorep plus gemcitabine in patients with advanced pancreatic adenocarcinoma has reported median overall survival of 10.2 months, with 1-year survival rate of 45% and 2-year survival rate of 24%.[128] The combination of pelareorep, atezolizumab, gemcitabine, and nanoparticle albumin-bound (nab)-paclitaxel has been granted fast track designation by the FDA following 69% objective response rate and complete response in 13 patients with advanced/metastatic pancreatic ductal adenocarcinoma enrolled in the phase 1/2 GOBLET study.

Racemetirosine

Oral racemetirosine (also known as SM-88), an oral inhibitor of the enzyme tyrosine 3-mono-oxygenase, has been investigated as a treatment for progressive or recurrent pancreatic cancer.[129] In pre-clinical studies, racemetirosine appeared to increase oxidative stress in cancer cells, disrupt autophagy, and modulate the tumour microenvironment by reducing the populations of M2 macrophages and regulatory T lymphocytes.[130] A subsequent platform trial was discontinued because racemetirosine did not demonstrate sufficient efficacy compared to standard chemotherapy regimens. Racemetirosine has been granted orphan drug designation by the FDA for the treatment of pancreatic cancer.

CEND-1

CEND-1 (also known as iRGD) is a peptide that preferentially binds integrins in tumour vasculature. Bound CEND-1 is cleaved by proteases to release a fragment that stimulates a novel drug uptake pathway, enhancing drug penetration into the tumour cells. CEND-1 has been granted fast track designation by the FDA. One phase 2 trial investigating the addition of CEND-1 to gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for patients with metastatic pancreatic cancer is underway.[131]

Efineptakin alfa

Efineptakin alfa is a long-acting human interleukin-7 fusion protein which acts by promoting T-cell development. A multicentre, open-label phase 1B/2A trial evaluating safety and efficacy of efineptakin alfa plus pembrolizumab in patients with advanced solid tumours, including pancreatic cancer, is in progress.[132] Efineptakin alfa has been granted orphan drug designation by the FDA for the treatment of pancreatic cancer.

Irreversible electroporation

Irreversible electroporation is a non-thermal ablation procedure for treating locally advanced unresectable pancreatic cancer (stage 3) that can be used in the proximity of sensitive structures such as vessels, intestinal wall, and the bile duct.[133][134][135] It can induce an immune response and has been found to be efficient in eliminating cancer cells in both in vitro and in vivo studies.[135] An improvement in median overall survival up to 30 months in patients with locally advanced unresectable pancreatic cancer has been noted.[134] Few centres in the UK are currently offering irreversible electroporation to selected patients. A clinical trial evaluating combination of irreversible electroporation plus immunotherapy for synergistic benefits is ongoing.[136]

Namodenoson

Namodenoson is a small molecule agonist of the A3 adenosine receptor, a receptor found on the surface of cancer cells but not on normal cells. Upon binding to this receptor, namodenoson induces apoptosis of cancer cells. Namodenoson has been granted orphan drug designation by the FDA for the treatment of pancreatic cancer. The FDA has also approved namodenoson for compassionate use on a case-by-case basis. One phase 2 trial assessing its safety and efficacy in treatment of pancreatic cancer is ongoing.[137]