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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04659096
• Other study ID #: ION537-CS1
• Status: Completed
• Phase: Phase 1
• Start date: January 5, 2021
• Est. completion date: October 19, 2022

Study information

• Verified date: December 2022
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 19, 2022
• Est. primary completion date: October 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• ION537
ION537 will be administered by IV injection.

Locations

Country	Name	City	State
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.	M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)