Clinical trial NCT05489237: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors
Official title: A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1]
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastrointestinal Stromal Tumor (GIST)
Digestive System Disease
Gastrointestinal Diseases
Metastatic Cancer
Keywords: GIST
IDRX
IDRX-42
Strate
StrateGIST
StrateGIST 1
Lead sponsor: IDRx, Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-05
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is the first clinical trial of IDRX-42. The study is designed to evaluate the safety, tolerability, PK, and preliminary antitumor activity of IDRX-42 in adult participants with advanced (metastatic and/or surgically unresectable) GIST.

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). In addition, a Concentration-QTc (C-QTc) substudy will be conducted in a subset of participants enrolled at selected sites in the study to characterize the effects of IDRX-42 on QTc and other ECG parameters in GIST patients.

Eligibility criteria: 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. Primary brain 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.

Primary outcomes:
measure: Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)
timeFrame: When participant completes 1 cycle (28 days) treatment with safety and tolerability assessment by investigators
measure: Phase 1 (Dose Escalation) - Safety and Tolerability (Nature, incidence, and severity of any DLTs)
timeFrame: Approximately 18 months from first participant enrolled
measure: Phase 1 (Dose Escalation) - Determination of the MTD and/or RP1bD(s) of orally administered IDRX-42
timeFrame: Approximately 18 months from first participant enrolled
measure: Phase 1 (Dose Escalation) - C-QTc sub-study: QTcF - concentration response analysis
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1b-Number of participants with TEAEs and with laboratory test results
timeFrame: Approximately 18 months
measure: Phase 1b - Objective Response Rate (ORR) mRESIST v1.1
timeFrame: Approximately 18 months
measure: Phase 1b - C-QTcF sub-study: QTcF - concentration response analysis
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Secondary outcomes:
measure: Phase 1 (Dose Escalation)- Number of participants with non-DLT TEAEs and with laboratory test results
timeFrame: 6 months
measure: Phase 1 (Dose Escalation) - ORR per mRECIST v1.1
timeFrame: 6 months
measure: Phase 1 (Dose Escalation) - Cmax; Maximum Observed Concentration of IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1 (Dose Escalation) - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1 (Dose Escalation) - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1 (Dose Escalation) - Duration of response (DOR) per mRECIST v1.1
timeFrame: 6 months
measure: Phase 1 (Dose Escalation) - Time to response (TTR) per mRECIST v1.1
timeFrame: 6 months
measure: Phase 1 (Dose Escalation) - Progression-free survival (PFS), per mRECIST v1.1
timeFrame: 6 months
measure: Phase 1 (Dose Escalation) - C-QTcF sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1b- Duration of response (DOR) per mRECIST v1.1
timeFrame: 18 months
measure: Phase 1b - PFS per mRECIST v1.1
timeFrame: 18 months
measure: Phase 1b - Clinical benefit rate (CBR) per mRECIST v1.1
timeFrame: 18 months
measure: Phase 1b - TTR per mRECIST v1.1
timeFrame: 18 months
measure: Phase 1b - Cmax; Maximum Observed Concentration of IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1b - Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1b - AUC 0-24; Area Under the Concentration-time Curve from Time Zero to 24 hours for IDRX-42
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
measure: Phase 1b - Overall survival
timeFrame: 18 months
measure: Phase 1b C-QTc sub-study: QTcF, heart rate, PR, QRS interval at baseline, post baseline and change from baseline.
timeFrame: At the end of Cycle 1 Day 1 and at the end of Cycle 2 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: Temple University Health System (Temple Health) - Fox Chase Cancer Center (FCCC) - Main Campus
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen (UZ) Leuven - Campus Gasthuisberg - Leuvens Kankerinstituut (Leuven Cancer Institute) (LKI)
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing Sheng
city: Guangzhou
country: China
facility: Sun-Yat-sen University - The Sixth Affliliated Hospital
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei Sheng
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai Sheng
city: Bordeaux
country: France
facility: Bergonie unicancer- Nouvelle Aquitaine - L'Institut Bergonie
state: Gironde
city: Lyon
country: France
facility: Centre de Lutte Contre le Cancer (CLLC) - Universite de Lyon -Centre Leon-Berard
state: Rhone
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille - Hopital de La Timone
city: Villejuif
country: France
facility: Centre de Lutte Centre le Cancer (CLCC) - Gustave Roussy
city: Berlin
country: Germany
facility: HELIOS Kliniken GmbH - HELIOS Klinikum Berlin-Buch
city: Essen
country: Germany
facility: University Hospital Essen-West German Cancer Center
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-Do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (SNUH)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital (Yonsei University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
state: North Holland
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center -Kanker Instituut
state: South Holland
city: Barcelona
country: Spain
facility: Vall d' Hebron Institute of Oncology (VHIO)
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
References: