LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.
MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.
In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.
The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.
Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.
The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).
Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).
At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.
In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.
In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.
In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.
Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.
Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.
“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”
Twelve patients were still receiving MRG-106 at last follow-up.
Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.
One patient was still in response at roughly 470 days of follow-up.
Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.
Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.
Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.
Dosing and administration
“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.
She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.
With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma Cmax.
She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.
AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).
Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).
There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.
The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.
The 300 mg IV infusion is the anticipated phase 2 dose.