MDNA11 Generates Activity, Safety in Advanced Solid Tumors

Treatment with the long-acting interleukin (IL)-2 superkine led to durable tumor control and no dose-limiting toxicities in patients with advanced solid tumors, according to data from the dose-escalation portion of the phase 1/2 ABILITY-1 trial (NCT05086692).¹

Findings showed that single-agent MDNA11 elicited tumor control in 37% of evaluable patients (n = 7/19). Additionally, 1 patient with metastatic pancreatic ductal adenocarcinoma (PDAC) experienced a confirmed partial response with an 80% decrease in total tumor size and complete regression in 2 of 3 lesions. This patient is continuing treatment in cohort 4 at a dose of 60 µg/kg after not responding to multiple prior systemic therapies.

Furthermore, 1 patient with metastatic melanoma whose disease progressed on prior immune checkpoint inhibition experienced stable disease for 84 weeks. This patient was in cohort 2, and after starting at a dose of 10 µg/kg, the dose was increased to 30, 60, and 90 µg/kg.

The dose-expansion portion of the study has commenced, with 90 µg/kg of MDNA11 given once every 2 weeks established as the recommended monotherapy dose for expansion. Dose expansion will include patients with melanoma, non-melanoma skin cancers, and microsatellite instability–high/mismatch repair–deficient tumors.

“We are pleased to see that MDNA11 continues to demonstrate durable single-agent activity in patients with advanced, treatment-refractory cancer, together with a manageable safety profile, and preserving its differentiated pharmacodynamic [PD] qualities, even though the phase 1 ABILITY study was not specifically designed to demonstrate efficacy,” Fahar Merchant, PhD, president and chief executive officer of Medicenna Therapeutics, stated in a news release.

“The promising therapeutic activity observed in patients who have progressed on multiple prior anti-cancer therapies, including a patient with a particularly aggressive form of cancer—PDAC—fuels our enthusiasm for initiating the dose expansion phase of the study,” Merchant continued. “The PD data supports [the] 90 [µg]/kg dose as the recommended dose for expansion, which will be evaluated in selected cancers that are most likely to benefit from MDNA11 monotherapy. We look forward to the upcoming readouts from the monotherapy dose expansion phase later this year and commencing the combination portion of the trial, where MDNA11 will be evaluated with [pembrolizumab (Keytruda)] as part of our clinical collaboration with Merck.”

MDNA11 is designed to preferentially bind to the beta receptor of IL-2 on immune cells to activate these cells to fight cancer.²

ABILITY is an open-label study enrolling patients at least 18 years of age with histologically or cytologically confirmed locally advanced or metastatic solid tumors. Patients are required to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 12 weeks.³

Key exclusion criteria include systemic anti-cancer therapy, including investigational agents, given within 4 weeks of enrollment, radiotherapy administered within 2 weeks of enrollment, radiotherapy of more than 30 Gy to the lung given within 6 months of study treatment, known central nervous system metastases and/or carcinomatous meningitis, or clinically active, known, or suspected autoimmune disease.

ABILITY plans to enroll approximately 104 patients, and MDNA11 is being administered once every 2 weeks in the monotherapy cohorts.1 The combination arm will examine MDNA11 plus pembrolizumab.

The primary end points of the study are to establish the recommended dose for expansion and evaluate the incidence of treatment-emergent and -related adverse effects. Secondary end points include PD and pharmacokinetics and antitumor activity.³

Among evaluable patients (n = 20) treated across 6 dose-escalation cohorts that evaluated MDNA11 monotherapy at doses ranging from 3 µg/kg to 120 µg/kg, 75% had received at least 1 prior line of immunotherapy.¹

PD data showed that MDNA11 led to robust expansion of activated CD8-positive T cells and increased natural killer cells with limited expansion of regulatory T cells that could suppress antitumor immunity.

Initial results from the dose-expansion portion of the study are expected in the fourth quarter of 2023.

References

1. Medicenna completes MDNA11 dose escalation and commences monotherapy dose expansion in the phase 1/2 ABILITY study. News release. Medicenna Therapeutics. August 9, 2023. Accessed August 9, 2023. https://ir.medicenna.com/news-releases/news-release-details/medicenna-completes-mdna11-dose-escalation-and-commences
2. Pipeline. MDNA11–an immune activation switch. Medicenna Therapeutics. Accessed August 9, 2023. https://www.medicenna.com/pipeline/mdna11/
3. A Beta-only IL-2 ImmunoTherapY Study (ABILITY-1). ClinicalTrials.gov. Updated June 29, 2023. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05086692