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

NCT03713320 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MRG106-11-2012018-000727-13
• Study Type: interventional
• Target: 37
• Locations: 8 countries
• Sites: 43

Brief Summary

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.

Conditions

Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Keywords

SOLAR; Cutaneous T-cell Lymphoma; CTCL; Mycosis Fungoides; Lymphoma; Lymphoma, T-cell; Lymphoma, T-cell, cutaneous; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms; MicroRNAs; Vorinostat; Histone Deacetylase Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Progression-free Survival (PFS)

  Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

• Complete Response Rate

  Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

• Time to 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

  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)

  Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

Other Outcomes (4)

• Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose

  1, 1.92, 6, 24 and 48 hours post-dose after the first dose

• Peak Plasma Concentration (Cmax) of Cobomarsen - 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

  1, 1.92 and 6 hours post-dose after the Week 5 dose

Study Arms (2)

Cobomarsen

EXPERIMENTAL

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

Vorinostat

ACTIVE COMPARATOR

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

Interventions

Cobomarsen DRUG

At least weekly doses of cobomarsen (282 mg) throughout study treatment period

Also known as: MRG-106

Cobomarsen

Vorinostat DRUG

Daily doses of vorinostat throughout study treatment period

Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• miRagen Therapeutics, Inc.: lead

Study Sites (43)

The University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UCLA

Los Angeles, California, 90404, United States

Location

Chao Family Comprehensive Cancer Center at University of California, Irvine

Orange, California, 92868, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63108, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Rochester Skin Lymphoma Medical Group

Fairport, New York, 14450, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Westmead Hospital

Westmead, New South Wales, NSW 2145, Australia

Location

Linear Clinical Research

Nedlands, 6009, Australia

Location

University Clinic UZ Leuven

Leuven, B3000, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hôpital Saint André, CHU de Bordeaux

Bordeaux, 33000, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69310, France

Location

Hôpital Robert Dubré, CHU de Reims

Reims, 51100, France

Location

Centre Hospitalier Universitaire de Rouen

Rouen, 76031, France

Location

Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

AOU Citta dell Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Fundación Jiménez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Consorcio Hospital General Universitario Valencia

Valencia, 46014, Spain

Location

University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust, Cancer Center

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33085815 DERIVED

• 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.

  PMID: 32632956 DERIVED

MeSH Terms

Conditions

Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Lymphoma; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms

Interventions

cobomarsen; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

The study was terminated early for business reasons, and not due to concerns regarding safety or lack of efficacy. Because the study was terminated early, enrollment was ended at 37 participants instead of the initially planned 126 participants, and a planned interim analysis based on these 37 participants was the only analysis performed for the study. The study duration was also shortened from an estimated 36 months to 20 months overall.

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Viridian Therapeutics (formerly miRagen Therapeutics)

clinicaltrials@viridiantherapeutics.com

720-722-5917

Study Officials

• Diana M. Escolar, MD, FAAN

  miRagen Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2018
• First Posted: October 19, 2018
• Study Start: April 2, 2019
• Primary Completion: October 12, 2020
• Study Completion: December 1, 2020
• Last Updated: April 8, 2022
• Results First Posted: April 8, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); IT (3); US (20); ES (5); BE (1); GB (4); AU (3); CA (2)