Phase 1/2, Open-label, Dose-escalation Study of IONIS-STAT3Rx, Administered to Patients With Advanced Cancers

Study Overview
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Brief Summary
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This is a Phase 1/2, open-label, dose-escalation, dose-expansion study for the treatment of patients with advanced cancers. Eligible patients with DLBCL or other advanced lymphomas will be enrolled into the dose-expansion cohort.

Official Title
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A Phase 1/2 Study of ISIS 481464, an Antisense Oligonucleotide Inhibitor of STAT3, Administered to Patients With Advanced Cancers

Conditions
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Advanced Cancers, DLBCL, Lymphoma

Intervention / Treatment
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* Drug: IONIS-STAT3Rx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older Tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists Expansion cohort only: Advanced lymphoma confirmed by histopathology Measurable or evaluable disease according to RECIST for solid tumors or according to IWRC for NHL tumors ECOG Performance Status less than or equal to 2 Life expectancy greater than 12 weeks in the opinion of the Investigator Exclusion Criteria: Any active or uncontrolled infection NYHA Grade II or greater congestive heart failure History of myocardial infarction within 6 months prior to screening Prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy within 4 weeks prior to screening or 5 half-lives of the therapy, whichever is shorter

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: Group 1<br>IONIS-STAT3Rx | Drug: IONIS-STAT3Rx<br>* Three-hour IV infusions on Cycle 0 Days 1, 3, 5, and weekly three-hour IV infusions in Cycles 1 and beyond, on Days 1, 8, and 15 of each cycle.<br>* Other names: ISIS 481464;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of IONIS-STAT3Rx in patients with Advanced Cancers |  | Approximately 28 days after last dose of IONIS -STAT3Rx | 
| Maximum-tolerated dose (MTD) of IONIS-STAT3Rx in patients with Advanced Cancers. | Highest dose level at which no more than 1 out of 6 patients develops a DLT | Approximately 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical activity of IONIS-STAT3Rx | Measured by RECIST in the study population who have measurable disease or relevant disease specific response criteria | Approximately 28 Days after last dose of IONIS-STAT3Rx | 
| Pharmacokinetics-Cmax | Maximum observed drug concentration (Cmax) | Approximately 28 days after last dose of IONIS-STAT3Rx | 
| STAT3 and other biomarkers | The effect of treatment with IONIS-STAT3Rx on phospho-STAT3 and other biomarkers | Approximately 28 days after last dose of IONIS-STAT3Rx | 
| Pharmacokinetics - Tmax | Time taken to reach Cmax | Approximately 28 days after last dose of IONIS-STAT3Rx | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancers, DLBCL, Advanced Lymphoma