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A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors

Primary Purpose

Gastrointestinal Stromal Tumor (GIST), Digestive System Disease, Gastrointestinal Diseases

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

IDRX-42

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor (GIST) focused on measuring GIST, IDRX, IDRX-42

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Phase 1

Male or female participants ≥18 years of age
Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST
Documented progression on imatinib (Phase 1)
Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing
At least one measurable lesion by mRECIST v1.1 for participants with GIST
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Resolution of any toxicities from prior treatment(s) to ≤ Grade 1 by NCI CTCAE v5.0 criteria, or have resolved to baseline, at the time of first dose of study drug.
Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.

Additional for Phase 1b Exploratory Cohorts

For Cohort 1, progressed on imatinib only (second line therapy)
For Cohort 2, progressed on both imatinib and sunitinib (third line therapy) or progressed on imatinib, sunitinib, and an additional agent (i.e., regorafenib or ripretinib) (fourth line therapy)
For Cohort 3, progressed on at all U.S. -approved TKI therapies for KIT-mutant GIST [imatinib, sunitinib, regorafenib, and ripretinib] (fifth line or greater therapy)

Exclusion Criteria:

Any prior exposure to the following investigational agents NB003 or THE-630 or bezuclastinib plus sunitinib combination.
GIST with no documented mutation in both KIT and PDGFRA genes.
Any prior primary CNS malignancy or known untreated or active central nervous system metastases.
Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.
Has significant, uncontrolled, or active cardiovascular disease.

Sites / Locations

University of MiamiRecruiting
Dana-Farber Cancer InstituteRecruiting
Oregon Health & Science University (OHSU)Recruiting
Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main CampusRecruiting
The University of Texas - MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Dose Escalation (Phase I)

(Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy

(Phase 1b): Cohort 2 - Participants with GIST progression after 2nd OR 3rd line TKI therapy

(Phase 1b): Cohort 3 - Participants with GIST progression after 4th or greater lines of TKI therapy

Arm Description

Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST.

Participants with advanced GIST who have had GIST progression only after first-line imatinib only (second line therapy setting).

Participants with metastatic and/or surgically unresectable GIST following progression EITHER after sequential imatinib then sunitinib (third-line therapy setting) OR after imatinib, sunitinib, and then an additional TKI agent (i.e., regorafenib or ripretinib) (fourth-line therapy setting).

Participants with advanced GIST who have had GIST progression after 4th line or greater lines of TKI therapy (failure due to progression of all available agents (imatinib, sunitinib, regorafenib, ripretinib, and possibly others (> 5th line therapy setting)

Outcomes

Primary Outcome Measures

Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)

Phase 1 (Dose Escalation) - Determination of the MTD and/or RP2DS of orally administered IDRX-42

Phase 1b-Number of participants with TEAEs and with laboratory test results

Phase 1b - Objective Response Rate (ORR) mRESIST v1.1

Secondary Outcome Measures

Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results

Phase 1 (Dose Escalation) - ORR per mRECIST v1.1

Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42

Phase 1 (Dose Escalation) - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42

Phase 1 (Dose Escalation) - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42

Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1

Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1

Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1

Phase 1b- Duration of response (DOR) per mRECIST v1.1

Phase 1b - PFS per mRECIST v1.1

Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1

Phase 1b - TTR per mRECIST v1.1

Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42

Phase 1b - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42

Phase 1b - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42

Phase 1b - Overall survival

Full Information

NCT ID

NCT05489237

First Posted

July 28, 2022

Last Updated

October 23, 2023

Sponsor

IDRx, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05489237

Brief Title

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors

Official Title

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 1, 2022 (Actual)

Primary Completion Date

April 24, 2026 (Anticipated)

Study Completion Date

September 13, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

IDRx, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is the first clinical trial of IDRX-42. The study is designed to evaluate the safety, tolerability, PK, and preliminary antitumor activity of IDRX-42 in adult participants with advanced (metastatic and/or surgically unresectable) GIST.

Detailed Description

This is a Phase 1/1b open-label, first-in-human FIH study of IDRX-42, an orally administered small molecule tyrosine kinase inhibitor. Eligible participants will have metastatic and/or surgically unresectable GIST, after failure of at least imatinib due to progression of GIST. The study consists of 2 parts. Phase 1 comprises dose escalation to assess clinical and pharmacologic profile, safety/tolerability, and support choice of the recommended phase 2 dose and schedule (RP2DS). Phase 1b expansion will enroll separate cohorts of participants defined by numbers of lines of prior GIST therapy at the selected RP2DS to assess the preliminary antitumor effect of IDRX-42 and further characterize the safety profile of IDRX-42 at the RP2DS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Stromal Tumor (GIST), Digestive System Disease, Gastrointestinal Diseases, Metastatic Cancer

Keywords

GIST, IDRX, IDRX-42

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

143 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose Escalation (Phase I)

Arm Type

Experimental

Arm Description

Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST.

Arm Title

(Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy

Arm Type

Experimental

Arm Description

Participants with advanced GIST who have had GIST progression only after first-line imatinib only (second line therapy setting).

Arm Title

(Phase 1b): Cohort 2 - Participants with GIST progression after 2nd OR 3rd line TKI therapy

Arm Type

Experimental

Arm Description

Arm Title

(Phase 1b): Cohort 3 - Participants with GIST progression after 4th or greater lines of TKI therapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

IDRX-42

Intervention Description

IDRX-42 will be administered at assigned doses and schedules once daily in continuous cycles of 28 days each.

Intervention Type

Drug

Intervention Name(s)

IDRX-42

Intervention Description

IDRX-42 will be administered at RP2DS once daily in continuous cycles of 28 days each.

Primary Outcome Measure Information:

Title

Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)

Time Frame

When participant completes 1 cycle (28days) treatment with safety and tolerability assessment by investigators

Title

Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)

Time Frame

Approximately18 months from first participant enrolled

Title

Phase 1 (Dose Escalation) - Determination of the MTD and/or RP2DS of orally administered IDRX-42

Time Frame

Approximately18 months from first participant enrolled

Title

Phase 1b-Number of participants with TEAEs and with laboratory test results

Time Frame

Approximately18 months

Title

Phase 1b - Objective Response Rate (ORR) mRESIST v1.1

Time Frame

Approximately 18 months

Secondary Outcome Measure Information:

Title

Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results

Time Frame

6 months

Title

Phase 1 (Dose Escalation) - ORR per mRECIST v1.1

Time Frame

6 months

Title

Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1 (Dose Escalation) - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1 (Dose Escalation) - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1

Time Frame

6 months

Title

Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1

Time Frame

6 months

Title

Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1

Time Frame

6 months

Title

Phase 1b- Duration of response (DOR) per mRECIST v1.1

Time Frame

18 months

Title

Phase 1b - PFS per mRECIST v1.1

Time Frame

18 months

Title

Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1

Time Frame

18 months

Title

Phase 1b - TTR per mRECIST v1.1

Time Frame

18 months

Title

Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1b - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1b - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42

Time Frame

At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)

Title

Phase 1b - Overall survival

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Phase 1 Male or female participants ≥18 years of age Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST Documented progression on imatinib (Phase 1) Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing At least one measurable lesion by mRECIST v1.1 for participants with GIST Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Resolution of any toxicities from prior treatment(s) to ≤ Grade 1 by NCI CTCAE v5.0 criteria, or have resolved to baseline, at the time of first dose of study drug. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions. Additional for Phase 1b Exploratory Cohorts For Cohort 1, progressed on imatinib only (second line therapy) For Cohort 2, progressed on both imatinib and sunitinib (third line therapy) or progressed on imatinib, sunitinib, and an additional agent (i.e., regorafenib or ripretinib) (fourth line therapy) For Cohort 3, progressed on at all U.S. -approved TKI therapies for KIT-mutant GIST [imatinib, sunitinib, regorafenib, and ripretinib] (fifth line or greater therapy) Exclusion Criteria: Any prior exposure to the following investigational agents NB003 or THE-630 or bezuclastinib plus sunitinib combination. GIST with no documented mutation in both KIT and PDGFRA genes. Any prior primary CNS malignancy or known untreated or active central nervous system metastases. Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics. Has significant, uncontrolled, or active cardiovascular disease.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

IDRX Clinical Operations

Phone

339-234-7028

clinicaltrials@idrx.com

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jonathan Trent, Dr.

Phone

305-243-8175

nxr518@med.miami.edu

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Suzanne George, MD

Phone

617-632-5204

Facility Name

Oregon Health & Science University (OHSU)

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Heinrich, MD

Phone

503-494-1080

trials@ohsu.edu

Facility Name

Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main Campus

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111-2497

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Margaret Von Mehren

Phone

215-728-2814

margaret.vonmehren@fccc.edu

Facility Name

The University of Texas - MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4000

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Neeta Somaiah

Phone

713-796-3626

NSomaiah@mdanderson.org

12. IPD Sharing Statement

Learn more about this trial

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors

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