SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides (SOLAR)

SOLAR: A Phase 2, Randomized, Open-label, Parallel-group, Active Comparator, Multi-center Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype

The main objective of this clinical trial is to study the efficacy and safety of cobomarsen (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) subtype. Cobomarsen is designed to inhibit the activity of a molecule called miR-155 that may be important to the growth and survival of MF cancer cells. The study will compare the effects of cobomarsen to vorinostat, a drug that has been approved for the treatment of CTCL in the United States and several other countries.

Participants in the clinical trial will be randomly assigned to receive either weekly doses of cobomarsen by injection into a vein or daily oral doses of vorinostat. Participants will continue on their assigned treatment as long as there is no evidence of progression of their cancer. The effects of treatment will be measured based on changes in skin lesion severity, as well as the length of time that the subject's disease remains stable or improved, without evidence of disease progression. The safety and tolerability of cobomarsen will be assessed based on the frequency and severity of observed side effects.

Participants assigned to receive vorinostat who experience progression of their disease during their participation in this study may have the option to be treated with cobomarsen in an open-label, crossover arm of the same study if they meet the entry criteria for that part of the study.

Study Overview

• Status: Terminated
• Conditions: Cutaneous T-Cell Lymphoma/Mycosis Fungoides
• Intervention / Treatment: Drug: Cobomarsen; Drug: Vorinostat

Detailed Description

Study Design:

Subjects will be randomly assigned in a 1:1 ratio to receive either cobomarsen or vorinostat. Approximately 126 subjects (63 per arm) are expected to be enrolled. Cobomarsen will be administered in the clinic by 2-hr intravenous infusion on Days 1, 3, 5 and 8, and weekly thereafter. Vorinostat will be dispensed to study subjects and taken as a daily oral dose according to the manufacturer's labeled dosing instructions. Treatment will continue until the subject becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated. An interim analysis will be conducted after approximately 40 subjects have been followed for a minimum of approximately 6 months. Enrollment will be suspended until the completion of the interim analysis.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Linear Clinical Research
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Westmead, New South Wales, Australia, NSW 2145
      • Westmead Hospital
• Belgium
  • Leuven, Belgium, B3000
    • University Clinic UZ Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• France
  • Bordeaux, France, 33000
    • Hôpital Saint André, CHU de Bordeaux
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Pierre-Bénite, France, 69310
    • Centre hospitalier Lyon-Sud
  • Reims, France, 51100
    • Hôpital Robert Dubré, CHU de Reims
  • Rouen, France, 76031
    • Centre Hospitalier Universitaire de Rouen
• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Torino, Italy, 10126
    • AOU Citta dell Salute e della Scienza di Torino
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario Valencia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West Of Scotland Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guy's and St. Thomas' NHS Foundation Trust, Cancer Center
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90404
      • UCLA
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California, Irvine
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale-New Haven
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Fairport, New York, United States, 14450
      • Rochester Skin Lymphoma Medical Group
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Biopsy-proven CTCL, MF subtype
• Clinical stage IB, II, or III, with staging based on screening assessments
• Minimum mSWAT score of 10 at screening
• Receipt of at least one prior therapy for CTCL

Key Exclusion Criteria:

• Previous enrollment in a cobomarsen study
• Prior therapy with vorinostat or other HDAC inhibitors, or contraindication to an HDAC inhibitor
• Sézary syndrome or mycosis fungoides with B2 involvement, defined as documented history of B2 and/or B2 staging at screening
• Evidence of large cell transformation
• Lymph node involvement at screening, unless radiologically or histologically confirmed to be nonmalignant
• Visceral involvement related to MF at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cobomarsen; Cobomarsen will be administered by intravenous 2-hour infusion at a dose of 282 mg on Days 1, 3, 5, 8, and weekly thereafter	Drug: Cobomarsen; At least weekly doses of cobomarsen (282 mg) throughout study treatment period; Other Names: MRG-106
Active Comparator: Vorinostat; Vorinostat will be administered orally at a dose of 400 mg (four 100-mg capsules) once daily with food, at approximately the same time each day.	Drug: Vorinostat; Daily doses of vorinostat throughout study treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)	ORR4 is the percentage of subjects with a complete response (CR) or partial response (PR) in the skin for 4 consecutive months confirmed by repeat assessments no less than 28 days (± 3 days) later. The modified Severity Weighted Assessment Tool (mSWAT) is used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores are calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores. Lower scores indicate a lower degree of skin disease severity. CR corresponds to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponds to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.	Date of first dose through the earlier of last study visit or interim analysis data cut-off date of 12-Oct-2020, up to 16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Time from date of randomization until the date of earliest documented progression or death from any cause. The duration of PFS was censored at the date of the last mSWAT assessment if the subject was alive and had no documented progression. Disease progression in the skin is defined as ≥ 25% increase in mSWAT score from baseline or, in participants with complete or partial response, increase in mSWAT score of greater than the sum of the nadir plus 50% baseline score.	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Complete Response Rate	Percentage of subjects with a complete response in the skin based on mSWAT	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Time to Progression	Time from date of randomization until the earliest date of confirmed progression	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Time to Maximal Effect in mSWAT	Time to greatest improvement in mSWAT score	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Objective Response Rate in the Skin of at Least 28-days Duration (ORR1)	Percentage of participants achieving ≥ 50% improvement in mSWAT of at least 28-days duration	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days	Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 28 days after first dose	28 days after first dose
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months	Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 4 months after first dose	4 months after first dose
Time to ≥ 50% Improvement in mSWAT	Time from date of randomization until ≥ 50% improvement in mSWAT score	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Duration of Response in Skin	Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT)	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Pruritus Medication Utilization	Change from baseline in number of pruritus medications taken per subject	Date of first dose through end of treatment or interim analysis data cut-off date of 12-Oct-2020, up to 16 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose	Peak plasma concentration (Cmax) of cobomarsen after first dose	1, 1.92, 6, 24 and 48 hours post-dose after the first dose
Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5	Peak plasma concentration (Cmax) of cobomarsen after fourth dose (Week 5)	1, 1.92 and 6 hours post-dose after the Week 5 dose
Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5	Area under the curve (AUClast) for cobomarsen plasma concentration versus time curve after the fourth (Week 5) dose	1, 1.92 and 6 hours post-dose after the Week 5 dose
Number of Participants With Anti-drug Antibody Generation	Number of participants who develop antibodies to cobomarsen during treatment	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

Collaborators and Investigators

• Sponsor: miRagen Therapeutics, Inc.

Publications and helpful links

General Publications

• Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.
• Ganguly K, Kishore U, Madan T. Interplay between C-type lectin receptors and microRNAs in cellular homeostasis and immune response. FEBS J. 2021 Jul;288(14):4210-4229. doi: 10.1111/febs.15603. Epub 2020 Nov 7. Review.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2019
• Primary Completion (Actual): October 12, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Immune System Diseases; Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Vorinostat; CTCL; Mycosis Fungoides; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphatic Diseases; Cutaneous T-cell Lymphoma; MicroRNAs; SOLAR; Lymphoma, T-cell; Lymphoma, T-cell, cutaneous; Histone Deacetylase Inhibitors
• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: MRG106-11-201; 2018-000727-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No