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

• ClinicalTrials.gov Identifier: NCT05489237
• Recruitment Status: Recruiting
• First Posted: August 5, 2022
• Last Update Posted: April 9, 2024
• Sponsor: IDRx, Inc.
• Information provided by (Responsible Party): IDRx, Inc.

Tracking Information

• First Submitted Date: July 28, 2022
• First Posted Date: August 5, 2022
• Last Update Posted Date: April 9, 2024
• Actual Study Start Date: August 1, 2022
• Estimated Primary Completion Date: April 24, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2024)

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

Original Primary Outcome Measures (submitted: August 3, 2022)

• 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 ]
• Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs) [ Time Frame: Approximately18 months from first participant enrolled ]
• Phase 1 (Dose Escalation) - Determination of the MTD and/or RP2DS of orally administered IDRX-42 [ Time Frame: Approximately18 months from first participant enrolled ]
• Phase 1b-Number of participants with TEAEs and with laboratory test results [ Time Frame: Approximately18 months ]
• Phase 1b - Objective Response Rate (ORR) mRESIST v1.1 [ Time Frame: Approximately 18 months ]

Current Secondary Outcome Measures (submitted: August 3, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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]
• 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]
• 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. 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
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastrointestinal Stromal Tumor (GIST)
• Digestive System Disease
• Gastrointestinal Diseases
• 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.
• Drug: IDRX-42
  IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.

Study Arms

• 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.
  Intervention: Drug: IDRX-42
• 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.
  Intervention: Drug: IDRX-42
• 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).
  Intervention: Drug: IDRX-42
• 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.
  Intervention: Drug: IDRX-42
• 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.
  Intervention: Drug: IDRX-42

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 5, 2024): 240
• Original Estimated Enrollment (submitted: August 3, 2022): 143
• Estimated Study Completion Date: September 13, 2026
• Estimated Primary Completion Date: April 24, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: IDRX Clinical Operations; 339-234-7028; clinicaltrials@idrx.com

• Listed Location Countries: Belgium, Germany, Spain, United States

Administrative Information

• NCT Number: NCT05489237
• Other Study ID Numbers: IDRX-42-001; StrateGIST 1 ( Other Identifier: IDRX, Inc. )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: IDRx, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: IDRx, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: IDRx, Inc.
• Verification Date: April 2024