Medicenna Partners with Italian Foundation to Launch NEO-CYT Trial Testing MDNA11 in High-Risk Melanoma
Key Insights
Medicenna Therapeutics (search) has partnered with Fondazione Melanoma Onlus (search) to launch NEO-CYT, a randomized neoadjuvant trial testing MDNA11 in combination with checkpoint inhibitors for high-risk Stage III melanoma (search) patients.
The trial will evaluate MDNA11's ability to enhance pathologic responses when combined with nivolumab alone or with ipilimumab, using Major Pathologic Response as the primary endpoint.
MDNA11 has demonstrated deep and durable responses in the ongoing ABILITY-1 study in heavily pretreated patients with advanced metastatic cancers.
Medicenna Therapeutics (search) Corp. has announced a collaboration with Italy's Fondazione Melanoma Onlus (search) to launch NEO-CYT, a randomized neoadjuvant trial evaluating MDNA11, the company's next-generation IL-2 Superkine, in combination with checkpoint inhibitors for patients with high-risk, surgically resectable Stage III cutaneous melanoma (search). The study represents a strategic move into earlier-stage disease where immune systems remain more responsive to treatment.
Trial Design and Objectives
NEO-CYT is a randomized, multi-center trial sponsored by Fondazione Melanoma Onlus (search) and led by Professor Paolo A. Ascierto of the Istituto Nazionale Tumori Fondazione "G. Pascale," a leading European cancer center. The study will evaluate MDNA11 in combination with nivolumab (anti-PD1) alone or with ipilimumab (anti-CTLA4), with Major Pathologic Response (MPR) serving as the primary endpoint.
"Neoadjuvant therapy has taught us that timing of immunotherapy matters," said Professor Ascierto. "Treating patients undergoing curative surgery while the tumor is still present can generate deeper and more durable immune responses. Advancing into the neoadjuvant setting represents a logical next-step in clinical development of any promising immunotherapy by treating earlier-stage, high-risk patients."
The trial design leverages pathologic response endpoints, which both predict long-term survival outcomes and may provide an efficient regulatory signal for immunotherapies. By evaluating pathologic response rates at the time of surgery in a randomized setting, NEO-CYT aims to provide an early, rigorous signal of activity.
MDNA11's Mechanism and Previous Results
MDNA11 is a long-acting, "beta-enhanced not-alpha" IL-2 Superkine engineered to overcome the shortcomings of aldesleukin and other next-generation IL-2 variants. The drug preferentially activates immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These features have been achieved by incorporating seven specific mutations and genetically fusing the molecule to a recombinant human albumin scaffold.
The albumin fusion improves the pharmacokinetic profile and pharmacological activity of MDNA11 due to albumin's natural propensity to accumulate in highly vascularized sites, particularly tumors and tumor-draining lymph nodes.
To date, MDNA11 has been studied in ABILITY-1 (NCT05086692), an ongoing Phase 1/2 study in advanced, treatment-refractory solid tumors as monotherapy and in combination with pembrolizumab. Early readouts have shown robust anti-tumor activity of MDNA11 both as single-agent and in combination with pembrolizumab in heavily pre-treated patients, including those who progressed on immune checkpoint inhibition, alongside expansion of effector lymphocytes and a manageable safety profile.
Strategic Implications
Fahar Merchant, Chief Executive Officer of Medicenna Therapeutics (search), emphasized the strategic importance of the collaboration: "We've already seen deep durable responses with MDNA11 in heavily pretreated patients with advanced metastatic cancers and profoundly compromised immune systems in the on-going ABILITY-1 trial. NEO-CYT is our next chapter — testing MDNA11 where the immune system is whole, the tumor can educate cancer fighting immune cells, and pathologic response gives a fast, rigorous signal of activity within weeks."
The neoadjuvant approach represents a significant expansion of MDNA11's potential market, moving from late-stage disease to the earliest line of systemic therapy for solid tumors. This positioning could potentially treat a large patient population with high-risk melanoma (search) and accelerate the clinical development strategy for MDNA11.
Collaboration Terms and Timeline
Under the clinical trial collaboration agreement, Fondazione Melanoma Onlus (search) serves as the sponsor while Medicenna will supply the study medications. The company expects to share updated clinical data from the ongoing ABILITY study at the upcoming ESMO-IO congress and results from the NEO-CYT study throughout 2026.
Medicenna's financial runway remains unchanged, with cash and equivalents expected to last into at least the middle of calendar 2026, providing sufficient resources to support the collaboration and ongoing development programs.