A first-in-human (FIH) study of IDRX-42 in participants with metastatic and/or unresectable gastrointestinal stromal tumors (GIST)

JRCT ID: jRCT2051240255

Registered date:31/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Metastatic and/or surgically unresectable gastrointestinal stromal tumors (GIST)
• Date of first enrollment: 28/02/2025
• Target sample size: 12
• Countries of recruitment: United States,,Japan,Belgium,Japan,Germany,Japan,Spain,Japan,France,Japan,South Korea,Japan,China,Japan,Netherlands,Japan,United Kingdom,Japan
• Study type: Interventional
• Intervention(s): IDRX-42 (tablet) 300 mg is administered orally once daily in 28-day cycle. May receive study drug until disease progression, unacceptable toxicity, death, withdrawal by participant, Investigator's decision to discontinue treatment, or Sponsor's decision to terminate the study.

Outcome(s)

Primary Outcome

Safety:
- Nature, incidence, and severity of TEAEs and change from baseline in laboratory results
Efficacy:
- Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 modified for participants with GIST (mRECIST v1.1, (Demetri 2013)) per Investigator assessment

Secondary Outcome

- Duration of response (DOR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
- progression-free survival (PFS) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
- Clinical benefit rate (CBR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
- Time to response (TTR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
- PK parameters of IDRX-42
- Overall survival (OS)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Phase 1
1.Male or female participants >- 18 years of age
2.Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST.
3.Documented progression on imatinib (Phase 1)
4.Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations determined through local testing.
5.At least 1 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 v5.0, or have resolved to baseline, at the time of first dose of study drug.
8.Able and willing to commit to study assessments and visit schedule.

Additional for Phase 1b Exploratory Cohorts
1.Cohort 1: progressed on imatinib only (second line therapy) and refused or are ineligible for other SOC therapies
2.Cohort 2: progressed on both imatinib and sunitinib (third-line therapy), or progressed on imatinib, sunitinib, and regorafenib (fourth-line therapy) or progressed on imatinib, sunitinib, regorafenib, and pimitespib (fifth-line or greater therapy)
3.Cohort 3: treatment naive (first line therapy) and refused or are ineligible for other SOC therapies
4.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

Exclude criteria

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).
1.GIST that is both KIT and PDGFRA wild-type.
2.Primary brain malignancy or known untreated or active central nervous system metastases.
3.Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.
4.Has significant, uncontrolled, or active cardiovascular disease.

Related Information

• Primary Sponsor: David Kerstein
• Secondary ID(s): NCT05489237