First Patient Receives IL-2 Superkine MDNA11 in Neoadjuvant Melanoma Trial

The first patient has been dosed in NEO-CYT (EUCT2024-519010-31-00), a phase 1b trial evaluating MDNA11 in combination with checkpoint inhibitors in patients with high-risk, surgically resectable stage III cutaneous melanoma, according to a news release from Medicenna Therapeutics.¹ The multicenter randomized, investigator-initiated trial sponsored by the nonprofit Fondazione Melanoma Onlus is enrolling at up to 12 sites in Italy and is led by Paolo A. Ascierto, MD, of the Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale” in Naples.

“Neoadjuvant therapy has demonstrated that the timing of immunotherapy can be critical,” Ascierto stated in the news release. “Treating patients while the tumor is still present may generate deeper and more durable immune responses.”

NEO-CYT represents the first evaluation of MDNA11, a long-acting, beta-enhanced IL-2 Superkine, in earlier-stage disease with curative intent, extending its clinical footprint beyond the heavily pretreated metastatic setting of the ongoing phase 1/2 ABILITY-1 study (NCT05086692).

Trial Design and End Points

NEO-CYT will evaluate MDNA11 in combination with nivolumab (Opdivo) with or without ipilimumab (Yervoy) administered prior to curative-intent surgery. The primary end point is major pathologic response (MPR), a surrogate end point considered predictive of long-term survival outcomes in the neoadjuvant setting. Nageatte Ibrahim, MD, chief medical officer at Medicenna, stated in the news release that in this patient population, “pathologic response can provide an early and rigorous sign of clinical activity.”

MDNA11: Mechanism and Prior Clinical Data

Designed to overcoming the limitations of aldesleukin (Proleukin), MDNA11 is engineered to preferentially activate CD8+ T cells and natural killer cells through selective binding to the IL-2 receptor beta subunit (CD122), while minimizing stimulation of immunosuppressive regulatory T cells by avoiding CD25 (IL-2 receptor alpha) binding. Seven targeted mutations and genetic fusion to a recombinant human albumin scaffold provide an extended pharmacokinetic profile and preferential accumulation in highly vascularized tissues, including tumors and tumor draining lymph nodes.

As of January 2026, over 110 patients have been enrolled in the multicenter, open-label dose-escalation phase 1/2 ABILITY-1 trial of MDNA11 for 29 different cancer types including cutaneous melanoma as a single agent or in combination with pembrolizumab (Keytruda).² The biologically effective dose range was established to be 60 to 120 g/kg. In the dose expansion cohorts from this trial, single-agent MDNA11 achieved a 37.5% overall response rate (ORR) among 8 evaluable patients with cutaneous melanoma with resistance to prior immunotherapy. In patients with any malignancy treated in the second or third line in the dose expansion cohorts, ORR was 50% across all monotherapy cohorts, and 42% as next-line treatment after failure of immune checkpoint inhibitor.

There were no dose-limiting toxicities in patients receiving up to 120 g/kg who had received up to 15 prior lines of therapy. The majority of treatment-related adverse events were grade 1 or 2 and resolved within 72 hours.³

Rationale Within the Current Standard of Care

The neoadjuvant setting has emerged as a critical treatment window for high-risk stage III melanoma. Results from the phase 3 NADINA trial (NCT04949113) demonstrated that neoadjuvant nivolumab plus ipilimumab, followed by therapeutic lymph node dissection and response-adapted adjuvant therapy, reduced the risk of progression, recurrence, or death by 68% compared with upfront surgery and adjuvant nivolumab alone, establishing combination checkpoint blockade as a new standard of care in this setting.⁴

NEO-CYT is designed to build on this backbone by investigating whether MDNA11 can further potentiate immune effector activity in patients whose immune systems remain relatively intact prior to systemic disease progression.¹

Next Steps

An initial poster presentation of the NEO-CYT study is planned for the 2026 American Society of Clinical Oncology Annual Meeting in Chicago on May 31^st.⁵ Results from NEO-CYT are anticipated to inform clinical development strategy and potential regulatory positioning of MDNA11 in the neoadjuvant melanoma setting.

“Dosing the first patient in the NEO-CYT study represents an important milestone in the continued clinical development of MDNA11 and expands our evaluation of this next-generation IL-2 Superkine into the neoadjuvant setting,” Ibrahim stated in the news release.¹

REFERENCES

1. Medicenna and Fondazione Melanoma Onlus Announce First Patient Dosed in the NEO-CYT Study of MDNA11 in Neoadjuvant Melanoma. News release. Medicenna Therapeutics. May 12, 2026. Accessed May 12, 2026. https://tinyurl.com/bdcbdtmy

2. Medicenna Therapeutics Announces Key Program Updates and 2026 Outlook. News release. Medicenna Therapeutics. January 15, 2026. Accessed May 12, 2026.https://tinyurl.com/4jtfmnzp

3. Atkinson VG, Brenner W, Brown JT, et al. Interim results from the phase 1/2 ABILITY-1 study of a long-acting ‘beta-enhanced not-alpha’ IL-2 superkine in patients with advanced solid tumors. Cancer Res. 2025;85(8_suppl_2):CT047. doi:10.1158/1538-7445.AM2025-CT047

4. Blank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Engl J Med. 2024. Doi: DOI: 10.1056/NEJMoa2402604

5. Medicenna and Fondazione Melanoma Onlus Announce Presentation on NEOCYT Trial at ASCO 2026. News release. Medicenna Therapeutics. April 30, 2026. Accessed May 12, 2026. https://tinyurl.com/mv83auv2