MDNA55 has been granted Orphan Drug status by USFDA and EMA (European Medicines Agency) for the treatment of gliomas and Fast Track designation for the treatment of GBM and anaplastic astrocytoma (AA) by the USFDA. MDNA55 is currently in late stage development for the treatment of recurrent GBM, a uniformly fatal form of brain cancer.
In previously completed clinical studies 72 patients with recurrent or progressive malignant gliomas (GBM and AA) were treated with MDNA55. More than 40% of the recurrent GBM (rGBM) subjects had multiple relapses or large tumors (>4cm in diameter) and 25% had a poor performance status (Karnofsky Performance Score; KPS of <70) prior to treatment with MDNA55. In two sponsor-initiated Phase 1/2a trials, all patients received a single infusion of MDNA55 using convection enhanced delivery (CED). In the first study, tumors were not resected, whereas in the second study, the tumors were resected 3 weeks post-treatment. Tumor response analysis was only performed in the first study.
There were no detectable levels of MDNA55 in the blood stream, nor any evidence of significant systemic toxicity following treatment. There were no deaths attributed to MDNA55. Adverse events (AEs) were primarily neurological which were generally transient and an aggravation of pre-existing neurological deficits anticipated in this patient population.
In the non-resected study, single treatment with MDNA55 was associated with a tumor response rate of 56% with a complete response (CR) rate of 20%. Further, the disease control rate (including stable disease) was 68%. Responses and tumor stabilization were durable, with a median duration of disease stabilization and response being 16 weeks. These findings are compelling when compared with response rates of less than 10% for historical controls and the 28% response rate that led to accelerated approval of Avastin. Further, among 25 unresected rGBM patients treated with MDNA55, an unprecedented CR rate of 20% was achieved when compared to 1.2% for Avastin.
Medicenna is currently enrolling patients in a Phase 2 clinical trial with MDNA55 for the treatment of rGBM at nine clinical sites in the United States.
The Phase 2 clinical trial, using enhanced Convection Enhanced Delivery (“CED”) is a multi-center, open-label, single-arm study in approximately 52 subjects with first or second recurrence or progression of GBM after surgery or radiotherapy ± adjuvant therapy or other experimental therapies.
The primary endpoint in the study is to determine the objective response rate (“ORR”) as per modified Response Assessment in Neuro-Oncology (“mRANO”) criteria following a single intra-and peri-tumoral infusion of MDNA55 in adult subjects with rGBM. The ORR will be assessed by gadolinium-enhanced MRI and determined by an independent blinded central imaging lab. The primary efficacy analysis will be assessed according to a single-stage binomial design with primary hypothesis test comparing a null ORR of 6% with an alternative (“pursue”) ORR of 18%, at 1-sided alpha – 0.20. The study will have 80% power with 23 evaluable subjects at the optimized dose.