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The FDA has greenlit an investigation new drug application to expand the ongoing phase 1/2 ABILITY trial, which is evaluating the beta-only IL-2 superagonist MDNA11 in patients with solid tumors, to clinical trial sites in the United States.
The FDA has greenlit an investigation new drug (IND) application to expand the ongoing phase 1/2 ABILITY trial (NCT05086692), which is evaluating the beta-only IL-2 superagonist MDNA11 in patients with solid tumors, to clinical trial sites in the United States.1
The trial is currently enrolling patients at sites throughout Australia, and regulatory submissions are seeking to further expand the trial to sites in Canada and the United Kingdom. These submissions are anticipated to be completed by the end of 2021.
“Clearance of this IND application is an important accomplishment that adds to the positive momentum behind our MDNA11 program,” Fahar Merchant, PhD, president and chief executive officer of Medicenna, stated in a press release. “We anticipate that the expansion of the ABILITY Study to the United States will expedite enrollment in the trial and advance the study toward key updates at the end of 2021 and mid-2022.”
The long-acting IL-2 superkine is fused with human recombinant albumin, which serves to increase its half-life and minimize dosing requirements without the cost of efficacy or toxicity.2 MDNA11 was developed to preferentially bind the IL-2 beta receptor on immune cells and to serve as a switch to activate and proliferate the immune cells required to eliminate cancer.
By binding to IL-2Rβ, the agent can preferentially stimulate both natural killer (NK) cells by 80-fold and naïve CD8 cells by 200-fold rather than immunosuppressive regulatory T cells vs native IL-2. This ultimately serves to overcome immune-suppressing cancer effects and activates cancer-killing immune cells that include cytotoxic T cells, naïve T cells, and NK cells.
Findings from preclinical research efforts have indicated that the investigative agent has demonstrated synergy when paired with checkpoint inhibitors, underscoring its potential for utilization in novel combination regimens.
The multicenter, open-label, dose-escalation and -expansion phase 1/2 ABILITY trial is enrolling patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors that are unresectable.3 Patients need to be at least 18 years of age, have an ECOG performance status of 0 or 1, have acceptable organ function, measurable disease per RECIST v1.1 criteria, and a life expectancy of at least 12 weeks.
If patients received an anticancer therapy within 28 days before the first study dose, had carcinomatous meningitis or leptomeningeal disease, an active malignancy within the 3 years prior to the study, or clinically significant, active, known, or suspected autoimmune disease, they were excluded. Other exclusion criteria comprised severe pulmonary, cardiac, or other systemic disease; active infection requiring systemic treatment; and previous interleukin therapy.
The study includes a monotherapy dose-escalation phase, which will be followed by an expansion phase, where MDNA11 will be evaluated in 2 arms: as a single agent at the recommended phase 2 dose (RP2D) and as part of combination with a checkpoint inhibitor. The investigative agent will be administered intravenously once every 2 weeks. Provisional dose cohorts for monotherapy dose escalations will range from 0.003 mg/kg to 0.6 mg/kg until the RP2D is determined.
The primary outcome measures for the trial include determining the RP2D for MDNA11, the incidence of treatment-related adverse effects (AEs), and the incidence of treatment-emergent AEs. Secondary outcome measures include examining the pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of MDNA11. Investigators will also conduct an analysis of immune characteristics of the tumor microenvironment.
The trial is anticipated to enroll approximately 80 patients, After the RP2D is established, Medicenna, the drug developer, plans to launch the dose-expansion phase of the trial, which will enroll patients with renal cell carcinoma, melanoma, and other solid tumors, who will receive either MDNA11 monotherapy or as part of a combination regimen.
We believe MDNA’s differentiated ‘beta-only’ approach to targeting the IL-2 receptor gives it the potential to overcome the shortcomings of other ‘not-alpha’ IL-2 agents and look forward to reporting the potential benefits of our approach as the study advances toward dose expansion and combination phases of the trial,” Merchant added in the press release.
A preliminary update on the safety, PK, PD, and biomarker findings from early cohorts enrolled in the dose-escalation portion of the research are anticipated by the end of 2021, and initial efficacy data are expected to be available in mid-2022.