Naptumomab estafenatox (naptumomab) is a tumor targeting immunotherapy that enhances the ability of the immune system to recognize and kill the tumor. Naptumomab is developed for treatment of solid tumors by Active Biotech’s partner NeoTX.
Type of substance:
Fusion protein
Effect:
Enhances the ability of the immune system to recognize and kill tumors
On this page:
Naptumomab in Brief
Naptumomab, a Tumor Targeting Superantigen (TTS), is a fusion protein containing the Fab-fragment of an antibody that targets the tumor-associated 5T4 antigen which is expressed in a high number of solid tumors.
The antibody part of naptumomab is fused with an engineered bacterial superantigen that activates specific T cells expressing a particular set of T cell receptors. In short, naptumomab functions by activating T cells and re-direct them to 5T4-expressing tumors. This leads to a massive infiltration of effector T cells into the tumor and tumor cell killing.
Binds to a tumour antigen (5T4)
Activates T cells
Enhances the immune response
Directs T cells to the tumour cell
Cancer is a collective name for a large group of diseases characterized by the growth of abnormal cells, which can invade adjacent parts of the body or spread to other organs. Cancer is the second most common cause of death in the world.
Naptumomab Activates and Directs T cells to the Tumor
Naptumomab increases the immune system’s ability to recognize and attack the tumor and preclinical data from various experimental models show synergistic anti-tumor effects and prolonged overall survival when naptumomab is combined with checkpoint inhibitors.
Checkpoint inhibitors are a group of cancer drugs which function by unleashing the immune system to attack the tumor. Despite the successes in recent years with these immunotherapies in the treatment of solid tumors, it remains a challenge for the immune system to recognize tumor cells and there is a need to optimize the therapeutic effect of checkpoint inhibitors.
Partner: NeoTXAstraZeneca
An open-label Phase Ib/II study of naptumomab in combination with durvalumab was initiated in 2019 in collaboration with AstraZeneca. Phase Ib has been completed and the recommended Phase II dose has been established.
Data from 59 patients with advanced/metastatic disease show that the treatment is well tolerated, with limited toxicity. Durable responses, including complete responses, were observed in patients where checkpoint inhibitors alone are not expected to be effective. Pre-treatment with obinutuzumab appears to reduce the development of anti-drug antibodies.
A cohort expansion in oesophageal cancer is active but not currently recruiting (NCT03983954).
Safety and tolerability of naptumomab as monotherapy and in combination with standard treatment have been established in clinical studies that include more than 300 patients.
Clinical development of naptumomab includes phase I studies in patients suffering from advanced non-small cell lung cancer, renal cell cancer and pancreatic cancer and a phase II/III study in combination with interferon alpha in patients with renal cell cancer.
Combining checkpoint inhibitors with the unique mode of action of naptumomab could be a useful strategy to treat multiple types of cancers, not responding to checkpoint inhibitors alone.
Ongoing
Phase I/II
An open-label, multicenter, dose-finding clinical phase Ib/II study is ongoing with naptumomab in combination with the checkpoint inhibitor durvalumab is ongoing.
Completed
Phase II
An open-label Phase IIa study in the US evaluated naptumomab in combination with docetaxel following obinutuzumab in patients with previously treated advanced/metastatic NSCLC. Results were presented at ASCO 2024.
A collection of Publications
Journal of Translational Medicine 2023 21:222
J Clin Oncol. 2009 Sep 1; 27 (25): 4116-23
NeoTXTherapeuticsLTD, Rehovot, Israel
Poster presentation at AACR Annual Meeting 2018