Gastrointestinal Stromal Tumors (GIST)Phase 1/2NCT05160168
A Study of THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
A Phase 1/2 study testing THE-630 in people with Gastrointestinal Stromal Tumors (GIST) and Neoplasms, Connective Tissue, run by Theseus Pharmaceuticals at 7 sites in United States.
Trial summary
This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors (GIST), Neoplasms, Connective Tissue, Neoplasms, Connective and Soft Tissue
- What is being tested?
- THE-630
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 7 sitesUnited States
- Study dates
- 3 Jan 2022to 2 Feb 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patient ≥18 years of age.
- For Dose Escalation Phase Cohorts (Phase 1):
- Have histologically- or cytologically-confirmed unresectable or metastatic GIST.
- Have progressed on or are intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib.
- For Expansion Phase Cohorts (Phase 2):
- Cohort 1:
Show all 26Show fewer
- Have histologically- or cytologically confirmed unresectable or metastatic GIST.
- Have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib.
- Cohort 2:
- Have histologically- or cytologically confirmed unresectable or metastatic GIST.
- Have progressed on or are intolerant to imatinib and sunitinib. Patients in this cohort are allowed to have received up to 1 additional line of therapy in the advanced/metastatic setting.
- Cohort 3:
- Have histologically- or cytologically confirmed unresectable or metastatic GIST.
- Have progressed on or are intolerant to imatinib (including in the adjuvant setting).
- Have not received additional systemic therapy for advanced GIST.
- Have at least 1 measurable lesion as defined by modified RECIST 1.1.
- Have archival or new tumor biopsy tissue available to submit for mutational testing. Patients without appropriate archival tissue available may be discussed with the study Medical Monitor and approved for enrollment on a case-by-case basis.
- Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
- Adequate renal and hepatic function as defined by the protocol.
- Adequate bone marrow function as defined by the protocol.
- For female patients of childbearing potential, have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to the first dose of study drug.
- o Note: female patients of nonchildbearing potential (postmenopausal; hysterectomy; bilateral salpingectomy; or bilateral oophorectomy) do not require a pregnancy test.
- Female patients of childbearing potential must agree to abstain from heterosexual intercourse or use a highly effective form of contraception with their sexual partners as defined in the study protocol. Male patients with partners of childbearing potential must agree that they will abstain from heterosexual intercourse or use condoms and their partners will use highly effective contraceptive methods as defined in the study protocol.
- All toxicities from prior therapy have resolved to Grade ≤1 according to NCI CTCAE v5.0, or have resolved to baseline, at the time of first dose of study drug. Note: treatment-related Grade >1 alopecia, treatment related Grade 2 peripheral neuropathy, and treatment-related Grade 2 hypothyroidism on a stable dose of thyroid hormone replacement therapy are allowed if deemed irreversible.
- Patient or legal guardian, if permitted by local regulatory authorities, signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study.
- Willingness and ability to comply with scheduled visits and study procedures.
Who cannot join
- Received systemic anticancer therapy (including cytotoxic chemotherapy, investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) less than 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study drug.
- Patients known to be both KIT and PDGFRA wild-type.
- Received radiotherapy within 14 days prior to the first dose of study drug.
- Major surgical procedure within 28 days of the first dose of study drug. Minor surgical procedures such as central venous catheter placement or minimally invasive biopsy are allowed.
- Have known untreated or active central nervous system metastases.
- 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula (QTcF) >470 msec at screening, or history of long QTc syndrome.
Show all 23Show fewer
- Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to:
- Myocardial infarction (MI) within 6 months prior to the first dose of study drug
- Unstable angina within 6 months prior to first dose of study drug
- Symptomatic congestive heart failure (New York Heart Association classes II-IV) within 6 months prior to first dose of study drug
- Clinically significant, uncontrolled atrial arrhythmia (as determined by the Investigator)
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
- Uncontrolled hypertension at study entry. Patients with hypertension should be under treatment on study entry to control blood pressure.
- Have an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.
- Patients with a known allergy or hypersensitivity to any component of the study drug. Patients with a history of Stevens-Johnson syndrome on a prior tyrosine kinase inhibitor (TKI) are excluded.
- Any active bleeding excluding hemorrhoidal or gum bleeding.
- For patients with a known human immunodeficiency virus (HIV) infection, have CD4+ T-cell counts <350 cells/uL or history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months. Patients with HIV infection should be on established antiretroviral therapy (ART) for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
- Has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as evidenced by detectable viral load (HBV-DNA or HCV-RNA, respectively). Risk of HBV reactivation should be considered in all patients and the need for anti-HBV prophylaxis should be carefully assessed. Patients with chronic HBV infection with history of active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy to be eligible for enrollment. Patients who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible. Patients on concurrent HCV treatment at the time of enrollment are allowed if HCV RNA negative.
- Pregnant or breastfeeding.
- Malabsorption syndrome or other illness that could affect oral absorption.
- Patients with prior or concurrent malignancies other than GIST are allowed, except in the case where, in the opinion of the Investigator, the natural history or treatment of the other malignancy has the potential to interfere with the safety or efficacy assessment of the study drug.
- Have any condition or illness that, in the opinion of the Investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Oregon Health & Science University
Portland, Oregon, 97239
HonorHealth Research Institute
Scottsdale, Arizona, 85258
About this study
Official title: A Phase 1/2 Study of the Safety, Pharmacokinetics and Anti-Tumor Activity of the Oral KIT Inhibitor THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST).
Read the detailed description
The drug being tested in this study is called THE-630, an orally administered KIT tyrosine kinase inhibitor. The study will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The patient population of the initial dose escalation phase (Phase 1) of the trial will include patients with unresectable or metastatic GIST. Patients must have disease progression on or be intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib. The primary objective of the dose escalation phase is to determine the safety profile of oral THE-630, including the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).
Once a recommended dose has been determined in the escalation phase, the expansion phase (Phase 2) will enroll 3 cohorts of patients with unresectable or metastatic GIST defined by prior therapy:
- Cohort 1: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib (≥5th Line).
- Cohort 2: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting (3rd-4th Line).
- Cohort 3: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST (2nd Line).
The safety and tolerability of orally administered THE-630 will continue to be assessed in the expansion cohorts. However, the primary objective of the expansion component of the trial is to evaluate the anti-tumor activity of THE-630 in these GIST patient populations.
- Conditions
- Gastrointestinal Stromal Tumors (GIST), Neoplasms, Connective Tissue, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms, Gastrointestinal Neoplasms
- Being tested
- THE-630
- Keywords
- Gastrointestinal Stromal Tumor, GIST, KIT inhibitor, THE-630, THE630, THE 630, GIST TKI, GIST tyrosine kinase inhibitor, GIST treatments, GIST Imatinib relapse, GIST Sunitinib relapse, GIST Regorafenib relapse, GIST Ripretinib relapse, PDGFRA, KIT-mutant GIST, Advanced GIST
- Medical subject headings
- Gastrointestinal Stromal Tumors, Neoplasms, Connective Tissue, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
THE-630Drug
Oral THE-630 administered once daily in a continuous regimen
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Participants with unresectable or metastatic GIST who will receive orally administered THE-630. Receives: Drug: THE-630 |
| Expansion Cohort 1 | Experimental | Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. Receives: Drug: THE-630 |
| Expansion Cohort 2 | Experimental | Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. Receives: Drug: THE-630 |
| Expansion Cohort 3 | Experimental | Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. Receives: Drug: THE-630 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630
Measured: 28 days
Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630
The MTD is defined as the highest dose at which ≤1 of 6 DLT-assessment eligible patients experience a DLT within the first 28 days of treatment (end of Cycle 1).
Measured: 28 days
Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630
The RP2D was expected to be equal to the MTD or less than the MTD, if aspects of tolerability or efficacy not encompassed by the MTD determination suggested utilizing a lower dose.
Measured: 28 days
Expansion (Phase 2): Efficacy Assessment - For Each Expansion Phase Cohort (Cohorts 1, 2, and 3), Confirmed Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Measured: Up to 24 months after first dose
Secondary outcomes (26)
Dose Escalation (Phase 1): Plasma Pharmacokinetic (PK) Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Duration of Response (DOR), According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1
Measured: 16 weeks
Dose Escalation (Phase 1): Efficacy Assessment - Progression Free Survival (PFS), According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Overall Survival (OS)
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - DOR, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - DCR, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - CBR at 16 Weeks, According to Modified RECIST 1.1
Measured: 16 weeks
Expansion (Phase 2): Efficacy Assessment - PFS, According to Modified RECIST 1.1
Measured: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - OS
Measured: Up to 24 months after first dose
Expansion (Phase 2): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events as Assessed by NCI CTCAE v5.0
Measured: Up to 24 months after first dose
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Measured: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2021
- Study start3 Jan 2022
- Primary completion2 Feb 2024
- Study completion2 Feb 2024
Why it stopped: The Sponsor terminated the study due to early dose-limiting toxicities.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastrointestinal Stromal Tumors (GIST)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theseus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stew Kroll, Study director, Theseus Pharmaceuticals (a subsidiary of Concentra Biosciences)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05160168
- Sponsor's protocol ID
- THE630-21-101
- Status last verified
- Jun 2024
- First submitted
- 22 Nov 2021
- Last updated
- 5 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of the Safety, Pharmacokinetics and Anti-Tumor Activity of the Oral KIT Inhibitor THE-630 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
- ClinicalTrials.gov ID
- NCT05160168
- Acronym / sponsor ID
- THE630-21-101
- Conditions
- Gastrointestinal Stromal Tumors (GIST), Neoplasms, Connective Tissue, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms, Gastrointestinal Neoplasms
- Keywords
- Gastrointestinal Stromal Tumor, GIST, KIT inhibitor, THE-630, THE630, THE 630, GIST TKI, GIST tyrosine kinase inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor terminated the study due to early dose-limiting toxicities.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Theseus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- 2 Feb 2024 (actual)
- Study completion
- 2 Feb 2024 (actual)
- First posted
- 16 Dec 2021 (actual)
- Results
- Posted 5 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST).
Detailed description
The drug being tested in this study is called THE-630, an orally administered KIT tyrosine kinase inhibitor. The study will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The patient population of the initial dose escalation phase (Phase 1) of the trial will include patients with unresectable or metastatic GIST. Patients must have disease progression on or be intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib. The primary objective of the dose escalation phase is to determine the safety profile of oral THE-630, including the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).
Once a recommended dose has been determined in the escalation phase, the expansion phase (Phase 2) will enroll 3 cohorts of patients with unresectable or metastatic GIST defined by prior therapy:
- Cohort 1: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib (≥5th Line).
- Cohort 2: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting (3rd-4th Line).
- Cohort 3: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST (2nd Line).
The safety and tolerability of orally administered THE-630 will continue to be assessed in the expansion cohorts. However, the primary objective of the expansion component of the trial is to evaluate the anti-tumor activity of THE-630 in these GIST patient populations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: THE-630Participants with unresectable or metastatic GIST who will receive orally administered THE-630. |
| Expansion Cohort 1 | Experimental | Drug: THE-630Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. |
| Expansion Cohort 2 | Experimental | Drug: THE-630Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. |
| Expansion Cohort 3 | Experimental | Drug: THE-630Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST, who will receive orally administered THE-630 at the recommended Phase 2 dose based on the dose escalation phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Male or female patient ≥18 years of age.
- For Dose Escalation Phase Cohorts (Phase 1):
- For Expansion Phase Cohorts (Phase 2):
- Have at least 1 measurable lesion as defined by modified RECIST 1.1.
- Have archival or new tumor biopsy tissue available to submit for mutational testing. Patients without appropriate archival tissue available may be discussed with the study Medical Monitor and approved for enrollment on a case-by-case basis.
Key exclusion criteria (23 listed)
- Received systemic anticancer therapy (including cytotoxic chemotherapy, investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) less than 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study drug.
- Patients known to be both KIT and PDGFRA wild-type.
- Received radiotherapy within 14 days prior to the first dose of study drug.
- Major surgical procedure within 28 days of the first dose of study drug. Minor surgical procedures such as central venous catheter placement or minimally invasive biopsy are allowed.
- Have known untreated or active central nervous system metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| THE-630Oral THE-630 administered once daily in a continuous regimen | Drug | Dose Escalation, Expansion Cohort 1, Expansion Cohort 2, Expansion Cohort 3 |
Primary outcome
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630
Time frame: 28 days
Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630
Time frame: 28 days
The MTD is defined as the highest dose at which ≤1 of 6 DLT-assessment eligible patients experience a DLT within the first 28 days of treatment (end of Cycle 1).
Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630
Time frame: 28 days
The RP2D was expected to be equal to the MTD or less than the MTD, if aspects of tolerability or efficacy not encompassed by the MTD determination suggested utilizing a lower dose.
Expansion (Phase 2): Efficacy Assessment - For Each Expansion Phase Cohort (Cohorts 1, 2, and 3), Confirmed Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: Up to 24 months after first dose
26 secondary outcomes
Dose Escalation (Phase 1): Plasma Pharmacokinetic (PK) Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Duration of Response (DOR), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1
Time frame: 16 weeks
Dose Escalation (Phase 1): Efficacy Assessment - Progression Free Survival (PFS), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Dose Escalation (Phase 1): Efficacy Assessment - Overall Survival (OS)
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - DOR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - DCR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - CBR at 16 Weeks, According to Modified RECIST 1.1
Time frame: 16 weeks
Expansion (Phase 2): Efficacy Assessment - PFS, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Efficacy Assessment - OS
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events as Assessed by NCI CTCAE v5.0
Time frame: Up to 24 months after first dose
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stew Kroll study director
Theseus Pharmaceuticals (a subsidiary of Concentra Biosciences)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing THE-630 in people with Gastrointestinal Stromal Tumors (GIST) and Neoplasms, Connective Tissue, run by Theseus Pharmaceuticals at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (time frame: Up to 24 months after first dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2024.