A First-In-Human (Fih) Study of IDRX-42 in Participants with Metastatic And/Or Unresectable Gastrointestinal Stromal Tumors (Gist)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Idrx Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Oct 2022 → ongoing

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

IDRX, Inc, a wholly owned subsidiary of GSK LLC

External identifiers

EU CT number

2024-514930-19-00

EudraCT number

2022-001192-14

ClinicalTrials.gov

NCT05489237

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Pharmacodynamic, Pharmacokinetic, Efficacy

Phase 1: Determine the maximum tolerated dose (MTD) and/or recommended Phase 1b dose(s) and schedule(s) RP1bD(s) of IDRX-42 in participants with metastatic and/or surgically unresectable GIST
Phase 1b:
-Safety: Further characterize the safety and tolerability of IDRX-42 in participants with metastatic and/or surgically unresectable GIST
- Efficacy: Evaluate the antitumor activity of IDRX-42 in participants with metastatic and/or surgically unresectable GIST
Phase 1 and 1b: C-QTc Sub-Study: (at select sites in the US, UK, Belgium, Spain, and Germany) Evaluate the relationship between IDRX-42 plasma exposure and QT interval corrected by Fridericia’s formula (QTcF)

Secondary objectives 3

1. Phase 1: (1) Assess the safety and tolerability of IDRX-42 in participants with metastatic and/or surgically unresectable GIST (2) Characterize the PK profile of IDRX-42 in participants with metastatic and/or surgically unresectable GIST (3) Evaluate preliminary antitumor activity of IDRX-42 in participants with metastatic and/or surgically unresectable GIST.
2. Phase 1b: (1) Further evaluate preliminary antitumor activity of IDRX-42 in participants with metastatic and/or surgically unresectable GIST (2) Characterize the PK profile of IDRX-42 in participants with metastatic and/or surgically unresectable GIST.
3. Phase 1 and 1b: C-QTc Sub-Study: Assess electrocardiogram (ECG) measurements by time point

Conditions and MedDRA coding

metastatic and/or unresectable gastrointestinal stromal tumors (GIST)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. ≥18 years of age, unless country specific standards require a different age for minors (e.g. ≥ 19 years of age in Korea).
2. 2. Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST.
3. 3. Documented progression on imatinib (Phase 1).
4. 4. Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing.
5. 5. At least 1 measurable lesion by mRECIST v1.1 for participants with GIST (Demetri 2013).
6. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. 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.
8. 8. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
9. 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 5

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 1: Nature, incidence, and severity of treatment-emergent adverse events (TEAEs) and DLTs.
2. 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
3. C-QTc Sub-Study: QTcF – concentration response analysis

Secondary endpoints 13

1. Phase1: (1) Nature, incidence, and severity of TEAEs and change from baseline in laboratory results.
2. Phase 1: (2) PK parameters of IDRX-42
3. 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
4. Phase 1: (4) Duration of response (DOR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
5. Phase 1: (5) Progression-free survival (PFS), per mRECIST v1.1 (Demetri 2013) per Investigator assessment
6. Phase 1: (6) Time to response (TTR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
7. Phase 1b: (7) DOR per mRECIST v1.1 (Demetri 2013) per Investigator assessment
8. Phase 1b: (8) PFS per mRECIST v1.1 (Demetri 2013) per Investigator assessment
9. Phase 1b: (9) Clinical benefit rate (CBR) per mRECIST v1.1 (Demetri 2013) per Investigator assessment
10. Phase 1b: (10) TTR per mRECIST v1.1 (Demetri 2013) per Investigator assessment
11. Phase 1b: (11) PK parameters of IDRX-42
12. Phase 1b: (12) Overall survival (OS)
13. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Idrx Inc.

Sponsor organisation

Idrx Inc.

Address

1250 South Road

City

Collegeville

Postcode

19426-2990

Country

United States

Scientific contact point

Organisation

Idrx Inc.

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Idrx Inc.

Contact name

EU GSK Clinical Trials Call Center

Third parties 8

Locations

6 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 131 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications