Gastrointestinal NeoplasmsPhase 1NCT05489237
First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors
A Phase 1 study testing IDRX-42 in people with Gastrointestinal Neoplasms and Gastrointestinal Stromal Tumor (GIST), run by IDRX, Inc., a wholly owned subsidiary of GSK, LLC at 31 sites in 11 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumor (GIST), Digestive System Disease
- What is being tested?
- IDRX-42
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- 31 sitesin 11 countries
- Study dates
- 3 Aug 2022to 26 Mar 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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) and refused or are ineligible for other standard of care (SOC) therapies.
- 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)
- 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.
- 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.
Who cannot join
- 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).
- GIST with no documented mutation in both KIT and PDGFRA genes.
- Primary brain 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.
Trial locations and contacts
31 sites in 11 countries.
31 sites in 11 countries
United States8 sites
GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
Chicago, Illinois, 60611
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
New York, New York, 10065-6007
GSK Investigational Site
Philadelphia, Pennsylvania, 19111-2434
GSK Investigational Site
Portland, Oregon, 97239
GSK Investigational Site
St Louis, Missouri, 63129
France4 sites
GSK Investigational Site
Bordeaux, 33076
GSK Investigational Site
Lyon
GSK Investigational Site
Marseille, 13005
GSK Investigational Site
Villejuif, 94805
South Korea4 sites
GSK Investigational Site
Seongnam-si Gyeonggi-do, 463-707
GSK Investigational Site
Seoul, 120-752
GSK Investigational Site
Seoul, 5505
GSK Investigational Site
Seoul, 6351
China3 sites
GSK Investigational Site
Beijing, 100142
GSK Investigational Site
Guangzhou
GSK Investigational Site
Wuhan, 430022
Japan3 sites
GSK Investigational Site
Chiba, 277-8577
GSK Investigational Site
Kanagawa, 247-8533
GSK Investigational Site
Tokyo, 104-0045
Germany2 sites
GSK Investigational Site
Berlin, 13125
GSK Investigational Site
Essen, North Rhine-Westphalia, 45122
Netherlands2 sites
GSK Investigational Site
Amsterdam, 1066 CX
GSK Investigational Site
Rotterdam, South Holland, 3075 EA
United Kingdom2 sites
GSK Investigational Site
Leeds, West Yorkshire, LS9 7TF
GSK Investigational Site
London, SW3 6JJ
About this study
Official title: A FIRST-IN-HUMAN (FIH) STUDY OF IDRX-42 IN PARTICIPANTS WITH METASTATIC AND/OR UNRESECTABLE GASTROINTESTINAL STROMAL TUMORS (GIST)
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.
Read the 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). In addition, a Concentration-QTc (C-QTc) substudy will be conducted in a subset of participants enrolled at selected sites in the study to characterize the effects of IDRX-42 on QTc and other ECG parameters in GIST patients.
- Conditions
- Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumor (GIST), Digestive System Disease, Gastrointestinal Diseases, Metastatic Cancer
- Being tested
- IDRX-42
- Keywords
- GIST, IDRX, IDRX-42, Strate, StrateGIST, StrateGIST 1, GSK6042981
- Medical subject headings
- Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors, Digestive System Diseases, Gastrointestinal Diseases, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IDRX-42Drug
Administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Phase I) | Experimental | Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST. Receives: Drug: IDRX-42 |
| (Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy | Experimental | 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. Receives: Drug: IDRX-42 |
| (Phase 1b): Cohort 2 - Participants with GIST progression after 2 or more lines of TKI therapy | Experimental | 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). Receives: Drug: IDRX-42 |
| (Phase 1b): Cohort 3 - Participants with GIST who are treatment naïve | Experimental | 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. Receives: Drug: IDRX-42 |
| (Phase 1b): Cohort 4 | Experimental | 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. Receives: Drug: IDRX-42 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)
Measured: 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)
Measured: Approximately 18 months from first participant enrolled
Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42
Measured: Approximately 18 months from first participant enrolled
Phase 1 (Dose Escalation) - C-QTc sub-study: QTcF - concentration response analysis
Measured: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Phase 1b-Number of participants with TEAEs and with laboratory test results
Measured: Approximately 18 months
Phase 1b - Objective Response Rate (ORR) mRESIST v1.1
Measured: Approximately 18 months
Phase 1b - C-QTcF sub-study: QTcF - concentration response analysis
Measured: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary outcomes (18)
Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results
Measured: 6 months
Phase 1 (Dose Escalation) - ORR per mRECIST v1.1
Measured: 6 months
Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42
Measured: 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
Measured: 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
Measured: 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
Measured: 6 months
Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1
Measured: 6 months
Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1
Measured: 6 months
Phase 1 (Dose Escalation) - C-QTcF sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.
Measured: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Phase 1b- Duration of response (DOR) per mRECIST v1.1
Measured: 18 months
Phase 1b - PFS per mRECIST v1.1
Measured: 18 months
Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1
Measured: 18 months
Phase 1b - TTR per mRECIST v1.1
Measured: 18 months
Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42
Measured: 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
Measured: 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
Measured: 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
Measured: 18 months
Phase 1b C-QTc sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.
Measured: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start3 Aug 2022
- Primary completion10 Mar 2027 (estimated)
- Study completion26 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 276 participants (actual)
Sponsor and investigators
- Lead sponsor
- IDRX, Inc., a wholly owned subsidiary of GSK, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05489237
- Sponsor's protocol ID
- 300382
- Other IDs
- IDRX-42-001, 2024-514930-19-00
- Status last verified
- Sep 2026
- First submitted
- 28 Jul 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available