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

NCT05489237
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Phase
Phase 1
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Recruitment status
Active, not recruiting
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Participants
276
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Lead sponsor
IDRX, Inc., a wholly owned subsidiary of GSK, LLC
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Start date
2022-08-03
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Number of sites
31
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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.
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Short title
First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors
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Official title
A FIRST-IN-HUMAN (FIH) STUDY OF IDRX-42 IN PARTICIPANTS WITH METASTATIC AND/OR UNRESECTABLE GASTROINTESTINAL STROMAL TUMORS (GIST)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-03-26
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First posted
2022-08-05
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Registry last updated
2026-07-02
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Primary completion date
2027-03-10
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Start date
2022-08-03
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Actual participants
276
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Participants
276
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
31
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
IDRX, Inc., a wholly owned subsidiary of GSK, LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05489237
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ClinicalTrials.gov ID
NCT05489237
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)

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

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

    Timeframe: Approximately 18 months from first participant enrolled

  3. Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42

    Timeframe: Approximately 18 months from first participant enrolled

  4. Phase 1 (Dose Escalation) - C-QTc sub-study: QTcF - concentration response analysis

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

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

    Timeframe: Approximately 18 months

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

    Timeframe: Approximately 18 months

  7. Phase 1b - C-QTcF sub-study: QTcF - concentration response analysis

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

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

    Timeframe: 6 months

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

    Timeframe: 6 months

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

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

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

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

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

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

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

    Timeframe: 6 months

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

    Timeframe: 6 months

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

    Timeframe: 6 months

  9. Phase 1 (Dose Escalation) - C-QTcF sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.

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

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

    Timeframe: 18 months

  11. Phase 1b - PFS per mRECIST v1.1

    Timeframe: 18 months

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

    Timeframe: 18 months

  13. Phase 1b - TTR per mRECIST v1.1

    Timeframe: 18 months

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

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

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

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

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

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

  17. Phase 1b - Overall survival

    Timeframe: 18 months

  18. Phase 1b C-QTc sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.

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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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 [US, UK, China, and Japan only], 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.

  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. Primary brain 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.
Sources for eligibility
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  • GSK Investigational SiteMiami, United States
  • GSK Investigational SiteChicago, United States
  • GSK Investigational SiteBoston, United States
  • GSK Investigational SiteSt Louis, United States
  • GSK Investigational SiteNew York, United States
  • GSK Investigational SitePortland, United States
  • GSK Investigational SitePhiladelphia, United States
  • GSK Investigational SiteHouston, United States
  • GSK Investigational SiteLeuven, Belgium
  • GSK Investigational SiteBeijing, China
  • GSK Investigational SiteGuangzhou, China
  • GSK Investigational SiteWuhan, China
  • GSK Investigational SiteBordeaux, France
  • GSK Investigational SiteLyon, France
  • GSK Investigational SiteMarseille, France
  • GSK Investigational SiteVillejuif, France
  • GSK Investigational SiteBerlin, Germany
  • GSK Investigational SiteEssen, Germany
  • GSK Investigational SiteMilan, Italy
  • GSK Investigational SiteChiba, Japan
  • GSK Investigational SiteKanagawa, Japan
  • GSK Investigational SiteTokyo, Japan
  • GSK Investigational SiteAmsterdam, Netherlands
  • GSK Investigational SiteRotterdam, Netherlands
  • GSK Investigational SiteSeongnam-si Gyeonggi-do, South Korea

And 6 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2024-514930-19-00
  • IDRX-42-001
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (3)