Medicenna announces single-agent activity of MDNA11 from dose expansion cohort

Medicenna Therapeutics (MDNA) presented updated clinical results from the ongoing monotherapy dose expansion and combination dose escalation portions of the Phase 1/2 ABILITY-1 study evaluating MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 super-agonist, as monotherapy or in combination with Merck’s (MRK) anti-PD-1 therapy, KEYTRUDA, in patients with advanced solid tumors, at the 39th Annual Meeting of the Society for Immunotherapy of Cancer, held in Houston, Texas, on November 9th, 2024. Key findings from the on-going monotherapy and combination dose escalation portions of the ABILITY-1 study at the time of data cut-off include: Monotherapy Tumor Response in Checkpoint Resistant Patients: MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumor activity among patients who progressed on prior ICI therapy: An objective response rate of 30% in the monotherapy dose expansion arm with 3 PRs among 10 patients who had all previously failed ICI therapy and had advanced and/or metastatic melanoma, non-melanoma skin cancer or MSI-H/dMMR tumors irrespective of tumor origin. The ORR is 25% from a total of 20 patients when including 10 phase 2 eligible patients from the MDNA11 monotherapy dose escalation arm who received at least 60 microgram/kg. Objective responses included: 2 PRs among 3 MSI-H patients with both responders having pancreatic ductal adenocarcinoma. One patient with MSI-H PDAC was initially misclassified as MSI-H small bowel cancer with metastases in the pancreas. 1 CR and 2 PRs among 11 patients with cutaneous melanoma. SD in 6 patients including 3 with duration greater than 24 weeks, yielding a clinical benefit rate of 40%. Monotherapy Safety Profile: Key findings from the monotherapy dose escalation and ongoing monotherapy expansion arms of the ABILITY-1 study demonstrate MDNA11’s favorable safety profile: As previously reported, DLT or vascular leak syndrome were not observed during monotherapy dose escalation with a majority of treatment-related adverse events being either grade 1 or 2 and resolving within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; one isolated grade 4 TRAE was observed with asymptomatic transient LFT elevation in the monotherapy dose expansion arm which resolved within 72 hours without intervention. Repeat administration of MDNA11 at the target doses continues to improve tolerability. Monotherapy Pharmacodynamics: Pharmacodynamic analyses showed potent and durable systemic immune responses following MDNA11 administration with clear evidence of immune activation in the tumor microenvironment: MDNA11 showed significant increases in markers of stemness, central and effector memory and enhanced effector function in circulating CD8+ T and NK cells. Analysis of paired biopsies showed increased tumor infiltration of CD25+ activated CD8+ T cells and NK cells post-MDNA11 treatment. Combination Dose Escalation Safety Profile: No DLTs, grade 4 or 5 TRAEs were observed in combination dose escalation cohorts 1 or 2 during the DLT observation period. The Safety Review Committee approved enrollment of the next higher-dose cohorts as follows: Cohort 3: 120 microgram/kg Q2W MDNA11 and 400 mg Q6W KEYTRUDA; Cohort 4: 120 microgram/kg Q3W MDNA11 and 400 mg Q6W KEYTRUDA. Combination Dose Escalation Pharmacodynamics: Early pharmacodynamic analyses demonstrated robust lymphocyte expansion which was sustained with repeat dosing at both 60 microgram/kg and 90 microgram/kg Q2W MDNA11 in combination with 400 mg Q6W KEYTRUDA. Combination Dose Escalation Tumor Response: Encouraging preliminary signs of anti-tumor activity were observed with MDNA11 in combination with KEYTRUDA in dose escalation cohorts 1 and 2. Among 5 heavily pre-treated efficacy-evaluable patients, tumor control was observed in 4 patients including a PR in a microsatellite-stable colon cancer patient.