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

Study Overview
=================
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Intervention / Treatment
-----------------
* Drug: Cobomarsen
* Drug: Vorinostat


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cobomarsen<br>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<br>* At least weekly doses of cobomarsen (282 mg) throughout study treatment period<br>* Other names: MRG-106;|
| Active Comparator: Vorinostat<br>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<br>* Daily doses of vorinostat throughout study treatment period<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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