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.

This is naptumomab

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.

Mode of Action for NAPTUMOMAB

Solid tumors

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. Lung, prostate, rectal, stomach and liver cancer are the most common types of cancer among men, while breast, rectal, lung, cervical and thyroid cancer are the most common types among women (

The market

Immunotherapy is one of the major breakthroughs of recent years in cancer therapy, which is reflected in the checkpoint inhibitors Keytruda, Opdivo, Imfinzi and Tecentriq achieving combined global sales of USD 22 billion in 2019 (Global Newswire February 2020). The strong sales development for checkpoint inhibitors is expected to continue and sales are forecast at USD 40 billion in 2025 (Global Newswire February 2020).

Current treatments

Treatment of solid tumors generally combines several types of therapy, which traditionally may include surgery, chemotherapy, and radiation therapy. Immunotherapy has been of decisive importance for cancer care in recent years and the immuno-oncology market has demonstrated strong growth. Therapies aimed at targeting immune suppression are dominated by biological drugs classified as checkpoint inhibitors. Several new checkpoint inhibitors have been approved for various types of solid tumors.

Naptumomab in solid tumors

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 over 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.

Ongoing clinical development

Two studies are currently in progress:

  • a phase Ib / II study with naptumomab in combination with durvalumab, a PD-L1 checkpoint inhibitor and
  • a Phase II study in combination with docetaxel in patients with non-small cell lung cancer.

More information about the ongoing studies can be found in the boxes below.

Previous clinical experience with naptumomab

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.

Naptumomab enhances tumor recognition

Phase Ib/II in advanced solid tumors


An open-label, multicenter, dose-finding clinical phase Ib/II study is ongoing with naptumomab in combination with the checkpoint inhibitor durvalumab. 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 Ib study before advancing to a phase II cohort expansion study. The trial was initiated in H2 2019 and is performed under an agreement with AstraZeneca. More information about the study is available at (NCT03983954) and at

Phase IIa study in combination with docetaxel in patients with non-small cell lung cancer


An open label clinical phase IIa study in US will assess naptumomab in combination with docetaxel in patients who had been previously treated with checkpoint inhibitors and have advanced or metastatic non-small cell lung cancer (NSCLC). On October 20, 2021, it was announced that the first patient was enrolled. The primary endpoint is objective response rate. In both ongoing studies patients are pre-treated with obinutuzumab to lower the levels of anti-drug antibodies (ADA) to naptumomab. For more information about the trial, visit (NCT04880863) and at


Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer. Hossein Borghaei, Katherine Alpaugh, Gunnar Hedlund, Göran Forsberg, Corey Langer, Andre Rogatko, Robert Hawkins, Svein Dueland, Ulrik Lassen, Roger B Cohen. J Clin Oncol. 2009 Sep 1; 27 (25): 4116-23.

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.

A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis. Hawkins R, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle Ö, Eisen T. Clin Cancer Res. 2016; 22(13): 3172-81

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

Naptumomab Estafenatox: targeted Immunotherapy with a Novel Immunotoxin. Eisen T, Hedlund G, Forsberg G, Hawkins R. Curr Oncol Rep. 2014; 16: 370

The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity. Hedlund G, Eriksson H, Sundstedt A, Forsberg G, Jakobsen BK, Pumphrey N, Rödström K, Lindkvist-Petersson K, Björk P. PLoS One. 2013; 8(10): e79082

Monotherapeutically Nonactive CTLA-4 Blockade Results in Greatly Enhanced Antitumor Effects When Combined With Tumor-targeted Superantigens in a B16 Melanoma Model. Sundstedt A, Celander M, Eriksson H, Törngren M, Hedlund G. J Immunother. 2012; 35(4): 344–53

Tumor-Targeted Superantigens, in Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges. Hedlund G, Forsberg G, Nederman T, Sundstedt A, Dahlberg L, Tiensuu M, Nilsson, M. (ed S. R. Schmidt) 2013; p365-381, John Wiley & Sons, Inc., Hoboken, NJ, USA

Naptumomab estafenatox: a new immunoconjugate. Robinson MK, Alpaugh KR, Borghaei H. Expert Opin Biol Ther. 2010; 10: 273-79

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