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

December 19, 2022 updated by: Ionis Pharmaceuticals, Inc.

Phase 1 Trial of ION537 in Patients With Molecularly Selected Advanced Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ION537
Multiple 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.
Drug: ION537
ION537 will be administered by IV injection.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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)
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)
Number of Participants With Dose-limiting Toxicities (DLTs)
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)
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)
Percentage of Participants With Complete Response (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)
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)
Percentage of Participants With Partial Response (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)
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)
Percentage of Participants With Stable Disease (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)
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)
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)
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)
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)
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)
Inhibition of Yes-associated Protein (YAP1) Expression
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)
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)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 5, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 19, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 19, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ION537-CS1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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