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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; DLBCL; Advanced Cancers
• Intervention / Treatment: Drug: IONIS-STAT3Rx

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • La Jolla, California, United States, 92093
      • Moores UC San Diego Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Blood and Marrow Transplant Group of Georgia at Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Texas
    • Dallas, Texas, United States, 75201
      • Mary Crowley Cancer Research Centers
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; IONIS-STAT3Rx	Drug: IONIS-STAT3Rx; 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.; Other Names: ISIS 481464

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.
• Collaborators: AstraZeneca
• Investigators: Study Director: Steve Hughes, MD, Ionis Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Reilley MJ, McCoon P, Cook C, Lyne P, Kurzrock R, Kim Y, Woessner R, Younes A, Nemunaitis J, Fowler N, Curran M, Liu Q, Zhou T, Schmidt J, Jo M, Lee SJ, Yamashita M, Hughes SG, Fayad L, Piha-Paul S, Nadella MVP, Xiao X, Hsu J, Revenko A, Monia BP, MacLeod AR, Hong DS. STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial. J Immunother Cancer. 2018 Nov 16;6(1):119. doi: 10.1186/s40425-018-0436-5.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2012
• Primary Completion (Actual): March 23, 2016
• Study Completion (Actual): March 23, 2016

Study Registration Dates

• First Submitted: February 13, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 26, 2012

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: DLBCL; Advanced Cancers; Advanced Lymphoma
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ISIS 481464-CS1