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

NCT05489237 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 300382IDRX-42-0012024-514930-19-00
• Study Type: interventional
• Target: 278
• Locations: 11 countries
• Sites: 31

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.

Conditions

Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumor (GIST); Digestive System Disease; Gastrointestinal Diseases; Metastatic Cancer

Keywords

GIST; IDRX; IDRX-42; Strate; StrateGIST; StrateGIST 1; GSK6042981

Outcome Measures

Primary Outcomes (7)

• 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 1 (Dose Escalation) - C-QTc sub-study: QTcF - concentration response analysis

  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

  Approximately 18 months

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

  Approximately 18 months

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

  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

  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)

Study Arms (5)

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.

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.

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).

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.

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.

Drug: IDRX-42

Interventions

IDRX-42 DRUG

Administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.

(Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy; (Phase 1b): Cohort 2 - Participants with GIST progression after 2 or more lines of TKI therapy; (Phase 1b): Cohort 3 - Participants with GIST who are treatment naïve; (Phase 1b): Cohort 4; Dose Escalation (Phase I)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IDRX, Inc., a wholly owned subsidiary of GSK, LLC: lead

Study Sites (31)

GSK Investigational Site

Miami, Florida, 33136, United States

RECRUITING

GSK Investigational Site

Chicago, Illinois, 60611, United States

RECRUITING

GSK Investigational Site

Boston, Massachusetts, 02215, United States

RECRUITING

GSK Investigational Site

St Louis, Missouri, 63129, United States

RECRUITING

GSK Investigational Site

New York, New York, 10065, United States

RECRUITING

GSK Investigational Site

Portland, Oregon, 97239, United States

RECRUITING

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

GSK Investigational Site

Houston, Texas, 77030, United States

RECRUITING

GSK Investigational Site

Leuven, 3000, Belgium

RECRUITING

GSK Investigational Site

Beijing, 100142, China

RECRUITING

GSK Investigational Site

Guangzhou, China

RECRUITING

GSK Investigational Site

Wuhan, 430022, China

RECRUITING

GSK Investigational Site

Bordeaux, 33076, France

RECRUITING

GSK Investigational Site

Lyon, France

RECRUITING

GSK Investigational Site

Marseille, 13005, France

RECRUITING

GSK Investigational Site

Villejuif, 94805, France

RECRUITING

GSK Investigational Site

Berlin, Germany

RECRUITING

GSK Investigational Site

Essen, 45122, Germany

RECRUITING

GSK Investigational Site

Milan, 20133, Italy

RECRUITING

GSK Investigational Site

Chiba, 277-8577, Japan

RECRUITING

GSK Investigational Site

Tokyo, 104-0045, Japan

RECRUITING

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

RECRUITING

GSK Investigational Site

Rotterdam, 3075 EA, Netherlands

RECRUITING

GSK Investigational Site

Seongnam-si Gyeonggi-do, 463-707, South Korea

RECRUITING

GSK Investigational Site

Seoul, 120-752, South Korea

RECRUITING

GSK Investigational Site

Seoul, 3080, South Korea

RECRUITING

GSK Investigational Site

Seoul, 5505, South Korea

RECRUITING

GSK Investigational Site

Seoul, 6351, South Korea

RECRUITING

GSK Investigational Site

Barcelona, Spain

RECRUITING

GSK Investigational Site

Leeds, LS9 7TF, United Kingdom

RECRUITING

GSK Investigational Site

London, SW3 6JJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Digestive System Diseases; Gastrointestinal Diseases; Neoplasm Metastasis

Interventions

IDRX-42

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 5, 2022
• Study Start: August 3, 2022
• Primary Completion (Estimated): March 10, 2027
• Study Completion (Estimated): June 28, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

FR (4); ES (1); DE (2); CN (3); GB (2); US (8); IT (1); BE (1); NL (2); KR (5); JP (2)