Clinical Trials /

A Study of ION537 in Patients With Molecularly Selected Advanced Solid Tumors

NCT04659096

Description:

The purpose of this study is to evaluate the safety and establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION537 when administered by intravenous infusion in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ION537 in Patients With Molecularly Selected Advanced Solid Tumors
  • Official Title: Phase 1 Trial of ION537 in Patients With Molecularly Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ION537-CS1
  • NCT ID: NCT04659096

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ION537ION537

Purpose

The purpose of this study is to evaluate the safety and establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION537 when administered by intravenous infusion in patients with advanced solid tumors.

Detailed Description

      This is a single center, open label, non-randomized, Phase 1, two-part study of ION537 in up
      to 102 participants. Part 1 of the study consists of sequential cohort, dose escalation in
      patients with advanced solid tumors. Part 2 is dose expansion in patients with molecularly
      selected advanced solid tumors. In total, the study includes up to 102 participants. The
      study will consist of a 30-day screening period, a treatment period consisting of sequential
      consecutive treatment cycles (each cycle will be of 28 days) and a post-treatment follow-up
      period of at least 28 days following the last dose of study drug.
    

Trial Arms

NameTypeDescriptionInterventions
ION537ExperimentalMultiple ascending doses of ION537 will be administered by intravenous (IV) injection on Days 1, 4, 8, 11, 15, and 22 in Cycle 1 and weekly dosing in each subsequent cycle until disease progression.
  • ION537

Eligibility Criteria

        Inclusion Criteria:

          1. Males and females ≥ 18 years old

          2. Participants must have histological diagnosis of local advanced (primary or recurrent)
             or metastatic solid tumors that are not amenable for treatment with curative intent

          3. Participants must be in need of systemic treatment for their cancer and either are
             refractory to or have failed treatment with, are intolerant to or have refused, or are
             not otherwise a candidate, in the opinion of the Investigator, for any of the
             currently available established therapies

          4. Participants must have available a fresh or recent tumor tissue sample from a
             diagnostic biopsy/surgery or a metastatic tumor biopsy;

          5. Participants must have measurable disease by response evaluation criteria in solid
             tumors (RECIST) v1.1; or participants may have bone metastatic disease evaluable by
             Prostate Cancer Working Group 2 (PCWG2) for participants with metastatic
             castration-resistant prostate cancer (mCRPC), or according to the tumor evaluation
             criteria best suited and accepted for the tumor type being evaluated

          6. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status
             (PS) 0 or 1

          7. Participants must be willing and able to comply with the scheduled visits, treatment
             plan, laboratory tests and other specified study procedures

        Exclusion Criteria:

          1. Known history or positive test for human immunodeficiency virus (HIV), hepatitis C
             virus (HCV) or chronic hepatitis B virus (HBV) infection.

          2. Active infection requiring intravenous (IV) antibiotics

          3. History of cerebrovascular accident (CVA), myocardial infarction or unstable angina
             within the previous 6 months before starting therapy.

          4. Participants with uncontrolled Type I or II diabetes mellitus (DM); uncontrolled DM

          5. Participants with prior anti-cancer therapy within 2 weeks prior to study enrollment
             or prior radiation therapy within 2 weeks prior to study enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Treatment-emergent Serious Adverse Event (TESAE), Graded by Severity
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With CR
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Percentage of Participants With PR
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Percentage of Participants With SD
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Duration of Response (DoR)
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Progression-free Survival (PFS)
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve from Hour Zero to Hour 24 AUC[0-24] for ION537
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Maximum Observed Plasma Concentration (Cmax) for ION537
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Time to Reach the Maximum Plasma Concentration (Tmax) for ION537
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:
Measure:Elimination Half-Life (t1/2) of ION537
Time Frame:Up to disease progression, death, start of new anticancer treatment, withdrawal of consent to study participation or end of the study, whichever occurs first (up to approximately 24 weeks for analysis)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ionis Pharmaceuticals, Inc.

Trial Keywords

  • Solid tumors
  • Advanced solid tumors

Last Updated

December 10, 2020