[4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL] (6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A] PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE for Gastrointestinal stromal tumour

Inclusion criteria

• {"criterion_text":"- 1. ≥18 years of age, unless country specific standards require a different age for minors (e.g. ≥ 19 years of age in Korea)."}
• {"criterion_text":"- 2. Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST."}
• {"criterion_text":"- 3. Documented progression on imatinib (Phase 1)."}
• {"criterion_text":"- 4. Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing."}
• {"criterion_text":"- 5. At least 1 measurable lesion by mRECIST v1.1 for participants with GIST (Demetri 2013)."}
• {"criterion_text":"- 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1."}
• {"criterion_text":"- 7. Resolution of any toxicities from prior treatment(s) to Grade ≤ 1 by NCI CTCAE v5.0, or have resolved to baseline, at the time of first dose of study drug. Note: unresolved prior treatment-related Grade 2 alopecia, Grade ≥2 peripheral neuropathy, and Grade ≥2 hypothyroidism on a stable dose of thyroid hormone replacement therapy are allowed if deemed irreversible."}
• {"criterion_text":"- 8. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions."}
• {"criterion_text":"- 9. Additional Inclusion Criteria for Phase 1b Exploratory Cohorts: (1)For Cohort 1, progressed on imatinib only (second line therapy) and refused or are ineligible for other 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 ripretinib (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. Note: If a participant received imatinib in the adjuvant or neoadjuvant setting only, they would be considered eligible for Cohort 3 provided recurrence/progression with metastatic and/or unresectable disease occurred more than 6 months after the last dose of (neo)adjuvant imatinib. (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. Please refer to the study protocol for a complete list of inclusion criteria."}

Exclusion criteria

• {"criterion_text":"- 1. Any prior treatment with investigational agents NB003 or THE-630 or a line of therapy of bezuclastinib plus sunitinib combination (except for participants treated in Cohort 4 of Phase 1b)."}
• {"criterion_text":"- 2. GIST that is both KIT and PDGFRA wild-type."}
• {"criterion_text":"- 3. Primary brain malignancy or known untreated or active central nervous system metastases."}
• {"criterion_text":"- 4. Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics."}
• {"criterion_text":"- 5. Has significant, uncontrolled, or active cardiovascular disease. Please refer to the study protocol for a complete list of exclusion criteria."}

Primary endpoints

• {"endpoint_text":"- Phase 1: Nature, incidence, and severity of treatment-emergent adverse events (TEAEs) and DLTs.","definition_or_measurement_approach":"Assessment of TEAEs and DLTs, severity/incidence recorded; toxicities referenced to NCI CTCAE v5.0."}
• {"endpoint_text":"- Phase 1b: (1) Safety: Nature, incidence, and severity of TEAEs and change from baseline in laboratory results (2) Efficacy: ORR per Response Evaluation Criteria in Solid Tumors version 1.1 modified for participants with GIST (mRECIST v1.1, (Demetri 2013), Appendix C) per Independent Review (IR)Investigator assessment","definition_or_measurement_approach":"Safety: TEAEs and laboratory changes from baseline. Efficacy: Objective response rate (ORR) assessed per mRECIST v1.1 (Demetri 2013) by Independent Review and Investigator assessment."}
• {"endpoint_text":"- C-QTc Sub-Study: QTcF – concentration response analysis","definition_or_measurement_approach":"Concentration–response analysis of QT interval corrected by Fridericia’s formula (QTcF) at defined post-dose time points."}

Secondary endpoints

• {"endpoint_text":"- Phase1: (1) Nature, incidence, and severity of TEAEs and change from baseline in laboratory results.","definition_or_measurement_approach":"Assessment of TEAEs and laboratory value changes from baseline (safety monitoring)."}
• {"endpoint_text":"- Phase 1: (2) PK parameters of IDRX-42","definition_or_measurement_approach":"Pharmacokinetic parameter measurement for IDRX-42 (standard PK sampling and analysis)."}
• {"endpoint_text":"- Phase 1: (3) Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 modified for participants with GIST (mRECIST v1.1, (Demetri 2013), Appendix C) per Investigator assessment","definition_or_measurement_approach":"ORR assessed by mRECIST v1.1 (Demetri 2013) by Investigator."}
• {"endpoint_text":"- Phase 1: (4) Duration of response (DOR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"DOR measured per mRECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 1: (5) Progression-free survival (PFS), per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"PFS determined per mRECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 1: (6) Time to response (TTR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"TTR assessed per mRECIST v1.1 by Investigator."}
• {"endpoint_text":"- Phase 1b: (7) DOR per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"DOR per mRECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 1b: (8) PFS per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"PFS per mRECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 1b: (9) Clinical benefit rate (CBR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"CBR assessed per mRECIST v1.1 by Investigator."}
• {"endpoint_text":"- Phase 1b: (10) TTR per mRECIST v1.1 (Demetri 2013) per Investigator assessment","definition_or_measurement_approach":"TTR per mRECIST v1.1 by Investigator assessment."}
• {"endpoint_text":"- Phase 1b: (11) PK parameters of IDRX-42","definition_or_measurement_approach":"Pharmacokinetic parameter measurement for IDRX-42 in Phase 1b cohorts."}
• {"endpoint_text":"- Phase 1b: (12) Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from date of first dose to death from any cause."}
• {"endpoint_text":"- C-QTc Sub-Study: (1)QTcF (QT interval corrected by Fridericia's formula) at each post-dose time point and baseline (2)Change from baseline in the QTcF at each post-dose time point (3)Heart rate (HR), PR and QRS (QRS complex) interval at each post-dose time point and baseline (4)Change from baseline in HR, QRS, and PR-interval at each post-dose time point","definition_or_measurement_approach":"Electrocardiogram measurements at scheduled time points: QTcF, HR, PR, QRS and change from baseline; concentration–response analysis."}

Methods

• Investigator/HCP referral letters (documents: Investigator referral letter / HCP referral letter) — targeted to healthcare professionals/investigators (present in country-specific recruitment materials).
• Patient flyer (K2_Recruitment material Patient Flyer) — print/digital flyers targeted to potential participants (present in country-specific recruitment materials).
• Patient website and Patient Website Awareness Card (K2_Recruitment material Patient Website / Patient Website Awareness Card) — web/online awareness materials targeted to patients (present in country-specific recruitment materials).
• Thank you card (K2_Recruitment material Thank You Card) — patient-facing follow-up material (present in country-specific recruitment materials).
• Patient Concierge service (third party: Scout Clinical) — participant support service as listed in third-party duties.

Netherlands

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

505

Number Of Sites

2

Number Of Participants

14

Italy

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

17-12-2025

Processing Time Days

506

Number Of Sites

1

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

17-12-2025

Processing Time Days

506

Number Of Sites

1

Number Of Participants

24

Germany

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

653

Number Of Sites

2

Number Of Participants

28

Belgium

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

653

Number Of Sites

1

Number Of Participants

28

France

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

653

Number Of Sites

4

Number Of Participants

30

Primary sponsor

Full Name

Idrx Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Clinipace Inc.

Name

Biotel Research LLC

Responsibilities

Imaging and ECG collection (Imaging Central Lab)

Name

Medidata Solutions Inc.

Responsibilities

Trial Supply management

Name

Scout Clinical

Responsibilities

Patient Concierge service

Third parties

• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"cfDNA and archival tissue samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"Imaging and ECG collection (Imaging Central Lab)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Concierge service","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"PK and cfDNA samples storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinipace Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Trial Supply management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Eurofins Adme Bioanalyses","duties_or_roles":"","organisation_type":"Pharmaceutical company"}