Nadunolimab Combo Hits 100% Complete Remission Rate in High-Risk MDS

Nadunolimab combined with azacitidine produced complete remissions (CRs) in all 5 evaluable patients with high-risk myelodysplastic syndrome (MDS) enrolled in the dose-escalation phase of an ongoing investigator-initiated phase 1b/2a trial (NCT06548230), according to Cantargia, the company developing the anti-IL1RAP antibody.¹

The trial is evaluating nadunolimab in combination with azacitidine in patients with high-risk MDS, or in combination with azacitidine and venetoclax (Venclexta) in patients with relapsed/refractory acute myelogenous leukemia (AML). Phase 1b dose escalation has been completed, with 6 patients enrolled in the MDS cohort and 6 in the AML cohort, and the study is now moving into the phase 2a portion.

"We are encouraged by the early clinical responses observed in high-risk MDS patients, particularly given the high unmet medical need in this population," Gautam Borthakur, MD, PhD, professor of Leukemia at MD Anderson Cancer Center, and principal investigator of the trial stated in a news release.¹ "Although the patient number remains small, the consistency of the responses and the manageable safety profile warrant further study as we continue trial enrollment."

MDS Cohort

Among the 6 patients dosed in the high-risk MDS cohort during phase 1b dose escalation, 5 were evaluable for efficacy at the time of the announcement, and all 5 achieved CRs. The sixth patient was pending evaluation. While the numbers are small and the data are preliminary, a 100% CR rate in a heavily pretreated population with high-risk MDS is a notable early signal, particularly given the limited treatment options available to patients who are ineligible for or have exhausted standard therapy. Further efficacy updates are anticipated as the phase 2a expansion progresses.

Safety of Nadunolimab

The safety profile of nadunolimab in combination with azacitidine or azacitidine and venetoclax was described as generally well tolerated across both patient groups, with an acceptable profile. No detailed adverse event data have been publicly disclosed from this cohort. The phase 1b dose-escalation design using standard 3+3 methodology was completed without requiring dose-limiting toxicities that would halt escalation, enabling advancement to phase 2a. Specific hematologic toxicities, including cytopenias, infection rates, and tolerability of the combination with azacitidine and venetoclax in the AML arm, remain unreported pending formal data disclosure.

Trial Design and Eligibility

The phase 1b/2a trial (NCT06548230) is an open-label, investigator-initiated study designed to evaluate the safety, recommended phase 2 dose (RP2D), and early efficacy of nadunolimab in 2 distinct arms. Arm 1 enrolls adults with intermediate-, high-, or very-high-risk MDS by revised International Prognostic Scoring System (IPSS-R) who are untreated or have received up to 2 prior lines of therapy, and these patients receive nadunolimab in combination with azacitidine. Arm 2 enrolls adults with relapsed/refractory AML receiving first or second salvage therapy, as well as patients with MDS or chronic myelomonocytic leukemia treated with hypomethylating agents who have progressed to AML without better available options; these patients receive nadunolimab in combination with azacitidine and venetoclax.²

Key inclusion criteria are age 18 years or older and ECOG performance status of 0 to 2. Patients with rapidly progressive disease requiring emergency cytoreduction as well as those with inadequate organ function are excluded. In the absence of rapidly progressing disease, a washout period of at least 2 weeks or 5 half-lives from prior therapy is required before initiating protocol therapy.

The primary objective is to determine the safety and RP2D of nadunolimab in each combination; secondary objectives include early efficacy, pharmacokinetics, immunogenicity, and exploratory biomarker analyses. The study is designed to enroll approximately 40 patients in total across both arms and is currently actively recruiting at MD Anderson.

"These data add to the growing body of clinical evidence supporting nadunolimab across our oncology programs," Hilde Steineger, chief executive officer of Cantargia, stated in the news release.¹ "Although based on a limited number of patients, the CR rate observed to date is encouraging and consistent with our understanding of IL1RAP targeting in combination with standard therapies."

REFERENCES

1. Cantargia AB. Cantargia announces early results from trial of nadunolimab in MDS and AML. News release. Cantargia AB; April 27, 2026. Accessed May 20, 2026. https://finance.yahoo.com/sectors/healthcare/articles/cantargia-announces-early-results-trial-052000007.html

2. Borthakur G. A phase 1b/2a trial of nadunolimab in combination with azacitidine (with/without venetoclax) in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). ClinicalTrials.gov identifier: NCT06548230. Updated September 2025. Accessed May 20, 2026. https://clinicaltrials.gov/study/NCT06548230