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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Diseases; Metastatic Cancer; Digestive System Disease; Gastrointestinal Stromal Tumor (GIST)
• Intervention / Treatment: Drug: IDRX-42; Drug: IDRX-42

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. 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).

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: IDRX Clinical Operations; Phone Number: 339-234-7028; Email: clinicaltrials@idrx.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg - Leuvens Kankerinstituut (Leuven Cancer Institute) (LKI)
    • Contact: Patrick Schöffski; Phone Number: +32 16 34 69 00; Email: trialunit@uzleuven.be
• Germany
  • Berlin, Germany, 13125
    • Recruiting
    • HELIOS Kliniken GmbH - HELIOS Klinikum Berlin-Buch
    • Contact: Annette Reichardt; Phone Number: +49 30 9401-14852; Email: annette.reichardt@helios-gesundheit.de
  • Essen, Germany, D - 45147
    • Recruiting
    • University Hospital Essen-West German Cancer Center
    • Contact: Sebastian Bauer; Phone Number: +49 (0) 201 / 723 2112; Email: sebastian.bauer@uk-essen.de
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d' Hebron Institute of Oncology (VHIO)
    • Contact: Silvia Espino; Phone Number: 4920 (+34) 93 274 60 00; Email: silviahurtado@vhio.net
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Jonathan Trent, MD; Phone Number: 305-243-8175; Email: nxr518@med.miami.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Suzanne George, MD; Phone Number: 617-632-5204
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University (OHSU)
      • Contact: Michael Heinrich, MD; Phone Number: 503-494-1080; Email: trials@ohsu.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Recruiting
      • Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main Campus
      • Contact: Margaret Von Mehren; Phone Number: 215-728-2814; Email: margaret.vonmehren@fccc.edu
  • Texas
    • Houston, Texas, United States, 77030-4000
      • Recruiting
      • The University of Texas - MD Anderson Cancer Center
      • Contact: Neeta Somaiah; Phone Number: 713-796-3626; Email: NSomaiah@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Phase I); Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST.	Drug: IDRX-42; IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.; Drug: IDRX-42; IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.
Experimental: (Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy; Participants with advanced GIST who have had GIST progression after first-line imatinib only (second line therapy setting) and refused or are ineligible for other standard of care (SOC) therapies.	Drug: IDRX-42; IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.; Drug: IDRX-42; IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.
Experimental: (Phase 1b): Cohort 2 - Participants with GIST progression after 2 or more lines of TKI therapy; 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) OR after imatinib, sunitinib, regorafenib, and ripretinib (5th line or greater therapy).	Drug: IDRX-42; IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.; Drug: IDRX-42; IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.
Experimental: (Phase 1b): Cohort 3 - Participants with GIST who are treatment naïve; Participants with metastatic and/or surgically unresectable GIST who are treatment naïve (first line therapy) and refused or are ineligible for other standard of care (SOC) therapies.	Drug: IDRX-42; IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.; Drug: IDRX-42; IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.
Experimental: (Phase 1b): Cohort 4; Participants with GIST progression who meet the same criteria as Cohort 2 (third line or greater TKI therapy) and have had prior treatment with investigational agents NB003 or THE-630 or a line of therapy of bezuclastinib plus sunitinib combination.	Drug: IDRX-42; IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.; Drug: IDRX-42; IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1b - Objective Response Rate (ORR) mRESIST v1.1	Approximately 18 months
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
Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)	Approximately 18 months from first participant enrolled
Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42	Approximately 18 months from first participant enrolled
Phase 1b-Number of participants with TEAEs and with laboratory test results	Approximately 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results	6 months
Phase 1 (Dose Escalation) - ORR per mRECIST v1.1	6 months
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)
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)
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)
Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1	6 months
Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1	6 months
Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1	6 months
Phase 1b- Duration of response (DOR) per mRECIST v1.1	18 months
Phase 1b - PFS per mRECIST v1.1	18 months
Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1	18 months
Phase 1b - TTR per mRECIST v1.1	18 months
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)
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)
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)
Phase 1b - Overall survival	18 months

Collaborators and Investigators

• Sponsor: IDRx, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): April 24, 2026
• Study Completion (Estimated): September 13, 2026

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: August 3, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: GIST; IDRX; IDRX-42; Strate; StrateGIST; StrateGIST 1
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms, Connective Tissue; Gastrointestinal Diseases; Digestive System Diseases; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: IDRX-42-001; StrateGIST 1 (Other Identifier: IDRX, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No