Medicenna Updates MDNA11 Clinical Trial Results at the ESMO-IO Congress 2025, Further Bolstering its Anti-Tumor Activity in Advanced Solid Tumors

Executive Summary

• Medicenna Therapeutics presented updated clinical data from the ongoing Phase 1/2 ABILITY-1 study at the ESMO Immuno-Oncology Congress 2025, demonstrating durable anti-tumor activity for MDNA11 in patients with advanced solid tumors, particularly those resistant to immune checkpoint inhibitors (ICI).
• MDNA11 monotherapy showed an Objective Response Rate (ORR) of 42% and Disease Control Rate (DCR) of 83% in Phase-2 eligible patients treated as the next line following ICI progression, with specific high response rates in melanoma (38% ORR) and MSI-H tumors (22% ORR).
• The combination of MDNA11 with KEYTRUDA (pembrolizumab) demonstrated significant activity in microsatellite stable (MSS) endometrial cancer (50% ORR) and TMB-H tumors (25% ORR), with disease control significantly associated with prolonged median overall survival in both monotherapy and combination cohorts.

Key Details

• Study Overview: Data presented from the global, multi-center, open-label Phase 1/2 ABILITY-1 study (NCT05086692) evaluating MDNA11 as a monotherapy or in combination with KEYTRUDA (pembrolizumab) for advanced solid tumors. Data cut-off was December 1, 2025.
• Safety Profile: MDNA11 demonstrated a manageable safety profile. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient. No dose-limiting toxicities (DLTs) were observed at doses up to 120 µg/kg in monotherapy or combination.
• Biological Effective Dose Range (BEDR): The preliminary recommended dose for expansion was established at 90 µg/kg Q2W, with a BEDR of 60 to 120 µg/kg (Q2W and Q3W).
• Monotherapy Results (ICI Resistant Patients):
  • Among Phase-2 eligible patients treated at the BEDR (N=22), the ORR was 42% (5 of 12) and DCR was 83% (1 CR, 4 PR, 5 SD) for patients treated as the next line following ICI progression.
  • Melanoma: ORR of 38% (3 of 8) with a DCR of 75% (1 CR, 2 PR, 3 SD) in 2° checkpoint-resistant cutaneous melanoma.
  • MSI-H Tumors: ORR of 22% (2 of 9) with a DCR of 78% (2 PR, 5 SD).
  • Long-term Remissions: Two patients achieved long-term remission, including a pancreatic MSI-H patient (>21 months off-treatment) and a melanoma patient (>7 months off-treatment).
• Combination Results (MDNA11 + KEYTRUDA):
  • Evaluated in patients who progressed on checkpoint therapy or were ineligible for ICI therapy (N=30).
  • MSS Endometrial Cancer: ORR of 50% (2 of 4) with a DCR of 75% (2 PR, 1 SD).
  • TMB-H Tumors: ORR of 25% (2 of 8) with a DCR of 88% (2 PR, 5 SD); tumor regression observed in 6 of 8 patients (75%).
  • Melanoma Case: A patient with cutaneous melanoma and primary resistance to standard of care (nivolumab + ipilimumab) achieved a Partial Response (PR) at the first on-study scan.
• Overall Survival (OS) Correlation:
  • Monotherapy: Patients with disease control (N=24) had a median OS of 120.2 weeks compared to 28.6 weeks in those without disease control (N=24) (p=0.002; HR 0.29 [95% CI: 0.13-0.66]).
  • Combination: Patients with disease control (N=27) had a median OS not yet reached compared to 26 weeks in those without disease control (N=18) (p=0.014, HR 0.28 [95% CI: 0.02-0.85]).
• Future Pipeline: The CEO highlighted the NEO-CYT trial sponsored by Fondazione Melanoma for pre-surgery high-risk melanoma and mentioned MDNA113 (a targeted anti-PD1-IL-2 BiSKIT) is anticipated to enter its first-in-human study later next year.

Notable Quotes

• Fahar Merchant, Ph.D., President and CEO: “The most important message from today’s data is that they absolutely add to the differentiation of MDNA11’s mechanism relative to other next-generation IL-2s and reinforce the consistency of its anti-tumor activity in late stage cancers refractory to checkpoint inhibitors... it is difficult for us not to conclude that MDNA11 demonstrates meaningful efficacy.”
• Dr. André Mansinho, Principal Investigator and Presenting Author: “I am encouraged by the durability of responses and the immune activation profile we observed with MDNA11, both as a single agent and combined with pembrolizumab. The clinical activity in checkpoint-resistant cohorts, together with prolonged remissions suggest a meaningful therapeutic signal that merits further evaluation in broader and earlier patient populations.”