Cantargia has enrolled the first patient in a Phase Ib/IIa clinical trial evaluating nadunolimab for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), marking the antibody's first application in hematological malignancies.
The investigator-initiated trial, funded by the US Department of Defense, will explore the safety and early efficacy of nadunolimab when combined with standard-of-care chemotherapies, specifically venetoclax and azacitidine. The study plans to enroll a total of 40 patients, evenly split between AML and MDS diagnoses, with complete recruitment anticipated by 2027.
Dr. Gautam Borthakur, professor of Leukemia at The University of Texas MD Anderson Cancer Center, serves as the principal investigator for this trial.
Scientific Rationale and Mechanism of Action
The trial builds upon a significant discovery by Professor Thoas Fioretos and Dr. Järås at Lund University, who identified that leukemia stem cells express interleukin-1 receptor accessory protein (IL1RAP) on their surface—a protein not expressed on normal hematopoietic stem cells.
Nadunolimab, an antibody that binds to IL1RAP, works through a dual mechanism: it blocks IL-1 mediated leukemia-promoting signals while also inducing antibody-dependent cellular cytotoxicity (ADCC), resulting in direct killing of tumor cells. This mechanism suggests therapeutic potential across multiple leukemia subtypes.
"I am thrilled to see the collaboration with the team at MD Anderson result in a study treating patients diagnosed with MDS and AML, since IL1RAP was initially discovered as a therapeutic target in patients diagnosed with these disorders," said Dr. Thoas Fioretos, professor at Lund University and a co-founder of Cantargia AB.
Study Design and Objectives
The primary objective of the trial is to evaluate safety and determine the recommended dosage of nadunolimab when used in combination with standard chemotherapies for leukemia. Secondary objectives include assessment of anti-tumor efficacy through overall response rates and duration of response in both AML and MDS patients.
The study will also conduct comprehensive translational research, investigating biomarkers, alterations in hematopoietic subpopulations, and effects on leukemic cells in blood and bone marrow. Single cell multimodal analysis will be performed at Lund University in Sweden.
Expanding Nadunolimab's Therapeutic Potential
"The potential for nadunolimab as anti-cancer therapy is expanded by this important investigator-led initiative treating patients with leukemias," said Dominique Tersago, Chief Medical Officer of Cantargia. "This is the first study of nadunolimab in hematological malignancies, and complements the promising results achieved with nadunolimab plus chemotherapy in solid tumor indications."
Nadunolimab has already demonstrated encouraging results in solid tumors. In the CANFOUR trial, the combination of nadunolimab with standard chemotherapy showed durable responses in pancreatic ductal adenocarcinoma (PDAC) patients, resulting in a median overall survival of 13.2 months. Even higher median overall survival of 14.2 months was observed in a subgroup of patients with high tumor levels of IL1RAP.
Similarly, in non-small cell lung cancer (NSCLC) patients, the combination therapy achieved a median progression-free survival of 7.2 months and a response rate of 55%, with even higher responses observed in non-squamous NSCLC patients.
Early efficacy data from the TRIFOUR trial also indicates promising results in triple-negative breast cancer, with a 60% response rate for nadunolimab combined with carboplatin/gemcitabine.
Addressing Unmet Needs in AML and MDS
AML and MDS represent significant unmet medical needs in hematological oncology. AML is an aggressive blood cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with normal blood cell production. MDS comprises a group of disorders where the bone marrow does not produce enough healthy blood cells, with a risk of progression to AML.
Current standard treatments for these conditions often have limited efficacy and substantial toxicity, particularly in older patients who represent the majority of cases. The exploration of nadunolimab in these indications could potentially offer new therapeutic options for patients with limited alternatives.
The trial is registered on clinicaltrials.gov under the identifier NCT06548230, where additional details can be found.
