Medicenna's MDNA11 Shows Promising Anti-Tumor Activity in Advanced Solid Tumors at ESMO-IO Congress 2025
核心洞察
Medicenna's MDNA11 demonstrated durable anti-tumor activity in phase-2 eligible expansion cohorts, achieving a 42% objective response rate in patients treated following immune checkpoint inhibitor progression.
The IL-2 super-agonist showed strong efficacy across multiple tumor types, with objective response rates of 38% in melanoma (搜索) and 22% in MSI-H cancers as monotherapy.
MDNA11 combined with pembrolizumab achieved 50% objective response rate in MSS endometrial cancer (搜索), demonstrating potential for combination therapy approaches.
Medicenna Therapeutics (搜索) presented compelling updated clinical data from its Phase 1/2 ABILITY-1 study at the European Society of Medical Oncology (ESMO) Immuno-Oncology Congress 2025, demonstrating that MDNA11, a long-acting IL-2 super-agonist, shows meaningful anti-tumor activity across multiple advanced solid tumor types.
Strong Efficacy in Checkpoint Inhibitor-Resistant Cancers
The most striking finding from the updated data was MDNA11's performance in patients who had progressed on immune checkpoint inhibitors (ICI). In monotherapy expansion cohorts, irrespective of tumor type, patients treated with MDNA11 as the next treatment following ICI progression achieved an objective response rate (ORR) of 42% and a disease control rate (DCR) of 83%.
"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," said Fahar Merchant, Ph.D., President and CEO of Medicenna.
Tumor-Specific Response Rates
The monotherapy expansion cohorts demonstrated notable efficacy across specific cancer types. In melanoma (搜索) patients, MDNA11 achieved an ORR of 38% with a DCR of 75%. For patients with MSI-H (microsatellite instability-high) cancers, the treatment showed an ORR of 22% and DCR of 78%.
Combination Therapy Results
When combined with Merck (搜索)'s KEYTRUDA (pembrolizumab), MDNA11 showed enhanced activity in certain tumor types. The combination achieved an ORR of 50% and DCR of 75% in MSS (microsatellite stable) endometrial cancer (搜索) patients. In MSS TMB-H (tumor mutational burden-high) tumors, the combination demonstrated an ORR of 25% and DCR of 88%.
Broad Anti-Tumor Activity
The study revealed that both monotherapy and combination treatments achieved durable responses across multiple advanced metastatic tumor types, including pancreatic, breast, colorectal, endometrial, bladder, anal cancer, and melanoma (搜索). Importantly, tumor control, defined as responders and those with stable disease, was associated with significantly prolonged median overall survival in both monotherapy and combination cohorts.
Mechanism and Future Development
MDNA11 is designed as a 'beta-enhanced not-alpha' interleukin-2 super-agonist with superior affinity toward CD122 (搜索) (IL-2 receptor beta) and no CD25 (搜索) (IL-2 receptor alpha) binding. This selective binding profile allows it to preferentially stimulate cancer-killing effector T cells and NK cells.
Merchant noted the recent announcement of the NEO-CYT trial sponsored by Fondazione Melanoma (搜索) in pre-surgery patients with high-risk melanoma as external validation of their approach. "This adds to our conviction that MDNA11 is potentially a de-risked drug candidate for earlier stage cancer patients harbouring healthier immune systems," he said.
The company plans to share additional mature data from the ABILITY-1 study in the coming months, along with new data from the NEO-CYT study and non-human primate data with MDNA113, their targeted anti-PD1-IL-2 BiSKIT anticipated to enter first-in-human studies next year.