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

Inclusion Criteria:

Phase 1

1. Male or female participants ≥18 years of age

2. Histologically or cytologically confirmed metastatic and/or surgically unresectableGIST

3. Documented progression on imatinib (Phase 1)

4. Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18mutations, 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 v5.0criteria, 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 areineligible for other standard of care (SOC) therapies.

2. For Cohort 2, progressed on both imatinib and sunitinib (third line therapy) orprogressed on imatinib, sunitinib, and an additional agent (i.e., regorafenib orripretinib) (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 havealso had prior treatment with investigational agents NB003 or THE-630 or a line oftherapy of bezuclastinib plus sunitinib combination.

Exclusion Criteria:

1. Any prior exposure to the following investigational agents NB003 or THE-630 orbezuclastinib 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 systemmetastases.

4. Has an active uncontrolled infection, including, but not limited to, the requirementfor intravenous antibiotics.

5. Has significant, uncontrolled, or active cardiovascular disease.