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

NCT04659096 | Completed Phase 1 FDA Drug

• 1 other identifier: ION537-CS1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

Solid tumors; Advanced solid tumors

Outcome Measures

Primary Outcomes (8)

• Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Treatment-emergent Serious Adverse Event (TESAE), Graded by Severity

  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)

  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)

  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)

  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)

  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

  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

  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

  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 Outcomes (12)

• Percentage of Participants With CR

  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

  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

  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)

  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)

  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)

Study Arms (1)

ION537

EXPERIMENTAL

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

Interventions

ION537 DRUG

ION537 will be administered by IV injection.

ION537

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years old
• Participants must have histological diagnosis of local advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent
• 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
• Participants must have available a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy;
• 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
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Participants must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures

You may not qualify if:

• Known history or positive test for human immunodeficiency virus (HIV), hepatitis C virus (HCV) or chronic hepatitis B virus (HBV) infection.
• Active infection requiring intravenous (IV) antibiotics
• History of cerebrovascular accident (CVA), myocardial infarction or unstable angina within the previous 6 months before starting therapy.
• Participants with uncontrolled Type I or II diabetes mellitus (DM); uncontrolled DM
• Participants with prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 9, 2020
• Study Start: January 5, 2021
• Primary Completion: October 19, 2022
• Study Completion: October 19, 2022
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)