PRISM: Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Mycosis Fungoides Who Have Completed the SOLAR Study

Study Overview
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Brief Summary
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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 in subjects who have confirmed disease progression following treatment with vorinostat in the SOLAR clinical study (MRG106-11-201). 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 effects of treatment will be measured based on changes in skin lesion severity, disease-associated symptoms, and quality of life, 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.

Detailed Description
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Study Design: Up to 60 subjects are expected to be enrolled after discontinuation from the SOLAR clinical study (MRG106-11-201). Cobomarsen will be administered in the clinic by 2-hr intravenous infusion on Days 1, 3, 5 and 8, and weekly thereafter. Treatment will continue until the subject becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated.

Official Title
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PRISM: An Open-label, Multi-Center Extension Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) Following Systemic Treatment in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype, Who Have Completed the SOLAR Study

Conditions
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Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Intervention / Treatment
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* Drug: Cobomarsen


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have participated in the comparator arm of the SOLAR clinical trial and completed the study (confirmed disease progression). Key Exclusion Criteria: 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. Visceral involvement related to MF at screening. Unresolved toxicities from prior vorinostat treatment, defined as having not resolved to CTCAE v5.0 grade 0 or 1. Any CTCL systemic therapy after completion of the SOLAR study and prior to Day 1 for PRISM.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cobomarsen<br> | Drug: Cobomarsen<br>* At least weekly intravenous infusions of cobomarsen (282 mg) throughout study treatment period<br>* Other names: MRG-106;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving an objective response of at least 4 months duration (ORR4) | Based on composite global response criteria including radiological imaging, flow cytometry, and the modified Severity Weighted Assessment Tool (mSWAT). | Up to approximately 36 months (estimated study duration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time from date of first dose of cobomarsen until the date of earliest documented progression or death from any cause. | Up to approximately 36 months (estimated study duration) | 
| Pruritis Numerical Rating Scale | Measures the patient's degree of itch related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no itch and 10 being worst imaginable itch. | Daily for up to 6 months, then weekly up to approximately 36 months (estimated study duration) | 
| Skindex-29 Dermatological Survey | Measures the effects of skin disease on quality of life based on a 30-item questionnaire. The patient's responses are transformed to a linear scale from 0 to 100 and averaged to determine a subscore in three domains (Symptoms, Emotions and Functioning), as well as a total score. Lower scores indicate a lesser degree of skin disease interference with quality of life. | Monthly, up to approximately 36 months (estimated study duration) | 
| Pain Numerical Rating Scale | Measures the patient's intensity of pain related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no pain and 10 being worst imaginable pain. | Daily, for up to 6 months, then weekly up to approximately 36 months (estimated study duration) | 
| Difference in drug tolerability by Patient Impression of Treatment Side Effects |  | Weekly, up to approximately 36 months (estimated study duration) | 
| Duration of composite global response for responding subjects |  | Up to approximately 36 months (estimated study duration) | 
| Complete response rate | Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT. | Up to approximately 36 months (estimated study duration) | 
| Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT) | Measures skin disease severity based on the percentage of skin within each body region with patches, plaques, or tumors. Total scores are calculated by adding the total percent for each category of lesion (patch, plaque, or tumor) and multiplying by a weighting factor. Weighted subtotals are added together to obtain the total score. Lower scores indicate a lower degree of skin disease severity. | Monthly, up to approximately 36 months (estimated study duration) | 
| Time to progression | Time from date of first dose of cobomarsen until the earliest date of confirmed progression. | Up to approximately 36 months (estimated study duration) | 
| Overall survival | Time from date of first dose of cobomarsen until the date of death from any cause. | Up to approximately 36 months (estimated study duration) | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |  | Up to approximately 36 months (estimated study duration) | 
| Plasma concentration of cobomarsen | Sparse pharmacokinetic samples will be collected to monitor for accumulation of cobomarsen. | Day 1, Day 29 and monthly or every other month thereafter until End of Treatment visit, up to approximately 36 months (estimated study duration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PRISM, 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