Naptumomab Estafenatox

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.

Mode of Action for NAPTUMOMAB

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.

Clinical Trials

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.

Naptumomab enhances tumor recognition

Phase Ib/II in advanced solid tumors


An open-label, multicenter, dose-finding clinical phase 1b/2 study with naptumomab in combination with durvalumab, a PD-1/L1 checkpoint inhibitor, is ongoing. The clinical trial will enroll patients with previously treated advanced or metastatic, 5T4-positive solid tumors and aims to establish the maximum tolerated dose in the phase IIb study before advancing to a phase II cohort expansion study. The trial was initiated in the second half of 2019 and is performed under an agreement with AstraZeneca. More information about the study is available at (NCT03983954) and

Phase I in solid tumors


In the clinical phase I trials, naptumomab was studied both as a single agent and in combination with an established tumor therapy – docetaxel (Taxotere®) – in patients with advanced lung cancer, renal cell cancer or pancreatic cancer (Borghaei et al, 2009; ClinicalTrials: NCT00056537 and NCT00132379). The results showed that naptumomab was well tolerated both as monotherapy and in combination with docetaxel. The phase I results also showed proof-of-concept in terms of increased immunologic activity, including systemic increase of inflammatory cytokines, expansion of naptumomab reactive T cells and induction of infiltrating T cells.

Phase II/III in renal cell cancer


Results from the naptumomab phase II/III clinical study in patients with advanced renal cell cancer were announced in January 2013 (Hawkins et al, 2016; Elkord et al, 2015). The study encompassed 513 patients and was designed to evaluate the effect of naptumomab in combination with interferon-alpha, compared with interferon-alpha alone. The phase II/III study did not achieve its primary endpoint showing a prolonged overall survival in the patient population. The safety profile was good and in line with previous observations.


Selective T cell Redirection Proteins (STR) Enhance the Anti-Tumor Activity of Checkpoint Inhibitors (CPIs) and can Lead to Long-Lasting Immunity Againstthe Tumor. Meir Azulay, Sveta Lifshits, EitanShany, Adam Friedmann, Gunnar Hedlund and Michal Shahar. NeoTXTherapeuticsLTD, Rehovot, Israel. View the complete poster here.

Naptumomab Estafenatox induces T cell recognition, turning anti-PD-1 unresponsive “cold” tumors into “hot” responsive tumors. Azulay M, Lifshits S, Fridman A, Hedlund G, Törngren M, Shahar M. Poster presentation at AACR Annual Meeting 2018. View the complete poster here.

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Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α. Elkord E, Burt DJ, Sundstedt A, Nordle Ö, Hedlund G, Hawkins R. Oncotarget. 2015; 6(6): 4428-39

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Naptumomab estafenatox, an engineered antibody-superantigen fusion protein with low toxicity and reduced antigenicity. Forsberg G, Skartved N-J, Wallén-Öhman M, Carlsson-Nyhlen H, Behm K, Hedlund G, Nederman T. J Immunother. 2010; 33: 492-9

Phase I dose escalation, pharmakokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non small-cell lung cancer. Borghaei H, Alpaugh K, Hedlund G, Forsberg G, Langer C, Rogatko A, Hawkins R, Dueland S, Lassen U, Cohen RB. J Clin Oncol. 2009; 27: 4116-23