A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1]

Metastatic Cancer Clinical Trial

Official title:

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1]

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05489237
• Other study ID #: IDRX-42-001
• Secondary ID: StrateGIST 1
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2022
• Est. completion date: September 13, 2026

Study information

• Verified date: April 2024
• Source: IDRx, Inc.
• Contact: IDRX Clinical Operations
• Phone: 339-234-7028
• Email: clinicaltrials[@]idrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. The study consists of 2 parts. Phase 1 comprises dose escalation to assess clinical and pharmacologic profile and safety/tolerability after failure of at least prior imatinib and support choice of the recommended phase 1b dose(s) and schedule(s) (RP1bDs)). Phase 1b expansion will enroll separate cohorts of participants defined by numbers of lines of prior GIST therapy at the selected RP1bD(s) to assess the preliminary antitumor effect of IDRX-42 and further characterize the safety profile of IDRX-42 at the RP1bD(s).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: September 13, 2026
• Est. primary completion date: April 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Phase 1

1. Male or female participants =18 years of age

2. Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST

3. Documented progression on imatinib (Phase 1)

4. Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing

5. At least one measurable lesion by mRECIST v1.1 for participants with GIST

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. 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.

8. 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

1. For Cohort 1, progressed on imatinib only (second line therapy) and refused or are ineligible for other standard of care (SOC) therapies.

2. 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) or progressed on imatinib, sunitinib, regorafenib, and ripretininb (fifth line or greater therapy)

3. For Cohort 3, treatment naïve (first line therapy) and refused or are ineligible for other standard of care (SOC) therapies.

4. For Cohort 4, met the same criteria as Cohort 2 (third line or greater) and have also had prior treatment with investigational agents NB003 or THE-630 or a line of therapy of bezuclastinib plus sunitinib combination.

Exclusion Criteria:

1. Any prior exposure to the following investigational agents NB003 or THE-630 or bezuclastinib plus sunitinib combination (except for participants treated in Cohort 4 of Phase 1b).

2. GIST with no documented mutation in both KIT and PDGFRA genes.

3. Any prior primary CNS malignancy or known untreated or active central nervous system metastases.

4. Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.

5. Has significant, uncontrolled, or active cardiovascular disease.

Related Conditions & MeSH terms

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

Intervention

Drug:
• IDRX-42
IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.
• IDRX-42
IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg - Leuvens Kankerinstituut (Leuven Cancer Institute) (LKI)	Leuven
Germany	HELIOS Kliniken GmbH - HELIOS Klinikum Berlin-Buch	Berlin
Germany	University Hospital Essen-West German Cancer Center	Essen
Spain	Vall d' Hebron Institute of Oncology (VHIO)	Barcelona
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida
United States	Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main Campus	Philadelphia	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
IDRx, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)		When participant completes 1 cycle (28 days) treatment with safety and tolerability assessment by investigators
Primary	Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)		Approximately 18 months from first participant enrolled
Primary	Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42		Approximately 18 months from first participant enrolled
Primary	Phase 1b-Number of participants with TEAEs and with laboratory test results		Approximately 18 months
Primary	Phase 1b - Objective Response Rate (ORR) mRESIST v1.1		Approximately 18 months
Secondary	Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results		6 months
Secondary	Phase 1 (Dose Escalation) - ORR per mRECIST v1.1		6 months
Secondary	Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1 (Dose Escalation) - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1 (Dose Escalation) - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1		6 months
Secondary	Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1		6 months
Secondary	Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1		6 months
Secondary	Phase 1b- Duration of response (DOR) per mRECIST v1.1		18 months
Secondary	Phase 1b - PFS per mRECIST v1.1		18 months
Secondary	Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1		18 months
Secondary	Phase 1b - TTR per mRECIST v1.1		18 months
Secondary	Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1b - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1b - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42		At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Phase 1b - Overall survival		18 months