Naptumomab Estafenatox, “naptumomab” is a tumor targeting immunotherapy that enhances the ability of the immune system to recognize and kill the tumor. Since October 2016, Active Biotech has a licensing agreement with NeoTX Therapeutics Ltd. for the worldwide development and commercialization of naptumomab for cancer therapy.
An open-label, multicenter, dose-finding clinical phase Ib/II study with naptumomab in combination with durvalumab, a checkpoint inhibitor, is ongoing. The clinical trial enrolls patients with previously treated advanced or metastatic, 5T4-positive solid tumors and aims to establish the maximum tolerated dose in the phase Ib study before advancing to phase II cohort expansion studies. In addition, a phase II study in combination with docetaxel in patients with non-small cell lung cancer (NSCLC) is expected to start in H2-2021 in the US.
Mode of Action and Therapy Concept
Naptumomab, a Tumor Targeting Superantigen (TTS), is a fusion protein containing the Fab-fragment of an antibody that targets the tumor-associated 5T4 antigen. 5T4 is expressed in a high number of solid tumors. The antibody part is fused with an engineered bacterial superantigen that activates T cells expressing a particular set of T cell receptors.
Naptumomab activates T lymphocytes and targets them to the 5T4-expressing tumors, resulting in massive effector lymphocyte infiltration into the tumor and tumor cell killing.
Naptumomab increases tumor recognition and redirect specific T cells to trigger tumor killing
So-called “programmed death 1/ligand 1” (PD-1/L1) antibodies are a new group of cancer drugs, checkpoint inhibitors, which function by unleashing the immune system to attack the tumor. Despite the successes of recent years with these immunotherapies, 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. Naptumomab increases the immune system’s ability to recognize and attack the tumor and preclinical data from several different experimental models show synergistic anti-tumor effects and prolonged overall survival when naptumomab is combined with checkpoint inhibitors.
The safety and tolerability of naptumomab as monotherapy and in combination with standard cancer therapy, has been established in clinical trials encompassing more than 300 patients. The previous clinical development of naptumomab includes phase I studies in patients with advanced non-small cell lung cancer, renal cell carcinoma and pancreatic cancer and a phase II/III trial in combination with interferon alpha in patients with renal cell carcinoma.