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JOURNAL ONKOLOGIE – STUDIE

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1]

Rekrutierend

NCT-Nummer:
NCT05489237

Studienbeginn:
August 2022

Letztes Update:
09.04.2024

Wirkstoff:
IDRX-42

Indikation (Clinical Trials):
Gastrointestinal Stromal Tumors, Gastrointestinal Diseases, Digestive System Diseases

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
IDRx, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 9)

HELIOS Kliniken GmbH - HELIOS Klinikum Berlin-Buch
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Annette Reichardt
Phone: +49 30 9401-14852
E-Mail: annette.reichardt@helios-gesundheit.de» Ansprechpartner anzeigen
University Hospital Essen-West German Cancer Center
D - 45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Sebastian Bauer
Phone: +49 (0) 201 / 723 2112
E-Mail: sebastian.bauer@uk-essen.de» Ansprechpartner anzeigen
Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main Campus
19111-2497 Philadelphia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Margaret Von Mehren
Phone: 215-728-2814
E-Mail: margaret.vonmehren@fccc.edu» Ansprechpartner anzeigen
The University of Texas - MD Anderson Cancer Center
77030-4000 Houston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Neeta Somaiah
Phone: 713-796-3626
E-Mail: NSomaiah@mdanderson.org» Ansprechpartner anzeigen
Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg - Leuvens Kankerinstituut (Leuven Cancer Institute) (LKI)
3000 Leuven
BelgiumRekrutierend» Google-Maps
Ansprechpartner:
Patrick Schöffski
Phone: +32 16 34 69 00
E-Mail: trialunit@uzleuven.be» Ansprechpartner anzeigen
Vall d' Hebron Institute of Oncology (VHIO)
08035 Barcelona
SpainRekrutierend» Google-Maps
Ansprechpartner:
Silvia Espino
Phone: (+34) 93 274 60 00
Phone (ext.): 4920
E-Mail: silviahurtado@vhio.net» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

Inclusion 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 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 v5.0

criteria, 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 are

ineligible for other standard of care (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 ripretininb (fifth line or greater therapy)

3. For Cohort 3, 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 have also

had prior treatment with investigational agents NB003 or THE-630 or a line of therapy

of bezuclastinib plus sunitinib combination.

Exclusion Criteria:

1. 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).

2. GIST with no documented mutation in both KIT and PDGFRA genes.

3. Any prior primary CNS malignancy or known untreated or active central nervous system

metastases.

4. Has an active uncontrolled infection, including, but not limited to, the requirement

for intravenous antibiotics.

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

Studien-Rationale

Primary outcome:

1. Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs) (Time Frame - When participant completes 1 cycle (28 days) treatment with safety and tolerability assessment by investigators)

2. Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs) (Time Frame - Approximately 18 months from first participant enrolled)

3. Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42 (Time Frame - Approximately 18 months from first participant enrolled)

4. Phase 1b-Number of participants with TEAEs and with laboratory test results (Time Frame - Approximately 18 months)

5. Phase 1b - Objective Response Rate (ORR) mRESIST v1.1 (Time Frame - Approximately 18 months)

Secondary outcome:

1. Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results (Time Frame - 6 months)

2. Phase 1 (Dose Escalation) - ORR per mRECIST v1.1 (Time Frame - 6 months)

3. Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

4. Phase 1 (Dose Escalation) - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

5. Phase 1 (Dose Escalation) - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

6. Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1 (Time Frame - 6 months)

7. Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1 (Time Frame - 6 months)

8. Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1 (Time Frame - 6 months)

9. Phase 1b- Duration of response (DOR) per mRECIST v1.1 (Time Frame - 18 months)

10. Phase 1b - PFS per mRECIST v1.1 (Time Frame - 18 months)

11. Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1 (Time Frame - 18 months)

12. Phase 1b - TTR per mRECIST v1.1 (Time Frame - 18 months)

13. Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

14. Phase 1b - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

15. Phase 1b - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42 (Time Frame - At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days))

16. Phase 1b - Overall survival (Time Frame - 18 months)

Studien-Arme

  • Experimental: Dose Escalation (Phase I)
    Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST.
  • Experimental: (Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy
    Participants with advanced GIST who have had GIST progression after first-line imatinib only (second line therapy setting) and refused or are ineligible for other standard of care (SOC) therapies.
  • Experimental: (Phase 1b): Cohort 2 - Participants with GIST progression after 2 or more lines of TKI therapy
    Participants with metastatic and/or surgically unresectable GIST following progression EITHER after sequential imatinib then sunitinib (third-line therapy setting) OR after imatinib, sunitinib, and then an additional TKI agent (i.e., regorafenib or ripretinib) (fourth-line therapy setting) OR after imatinib, sunitinib, regorafenib, and ripretinib (5th line or greater therapy).
  • Experimental: (Phase 1b): Cohort 3 - Participants with GIST who are treatment naïve
    Participants with metastatic and/or surgically unresectable GIST who are treatment naïve (first line therapy) and refused or are ineligible for other standard of care (SOC) therapies.
  • Experimental: (Phase 1b): Cohort 4
    Participants with GIST progression who meet the same criteria as Cohort 2 (third line or greater TKI therapy) and have had prior treatment with investigational agents NB003 or THE-630 or a line of therapy of bezuclastinib plus sunitinib combination.

Geprüfte Regime

  • IDRX-42:
    IDRX-42 will be administered at assigned doses and schedules once or twice daily in continuous cycles of 28 days each.
  • IDRX-42:
    IDRX-42 will be administered at RP1bD(s) once or twice daily in continuous cycles of 28 days each.

Quelle: ClinicalTrials.gov


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