A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST1]

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST1]

Gastrointestinal Stromal Tumor

Recruiting

1

Start Date 08/01/2022

Age of Trial (yrs) 2

Gleevec-resistant

KIT/PDGFRA inhibitor

Block KIT/PDGFRA

Specifically GIST and only GIST

IDRX-42-001 StrateGIST 1

IDRx, Inc.

IDRX Clinical Operations 339-234-7028 clinicaltrials@idrx.com

Oral

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).

Inclusion Criteria:

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, 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.

Exclusion Criteria:

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.
Any prior primary CNS 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.