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

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: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ION537

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: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas 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:

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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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	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 Outcome Measures

Outcome Measure	Time Frame
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)
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)
Duration of Response (DoR)	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)	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)	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	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	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

• Sponsor: Ionis Pharmaceuticals, Inc.
• Collaborators: M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Solid tumors; Advanced solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID 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