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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)
EU CTIS ID: 2022-502087-21-00
What this study is testing
Dose Escalation (Phase 1): To determine the safety profile of oral THE-630, including the DLTs, MTD, and RP2D. Expansion (Phase 2): To determine the antitumor activity of oral THE-630 in patients with advanced GIST.
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male or female patient ≥ 18 years of age.
- Female patients of childbearing potential must agree to abstain from heterosexual intercourse or use a highly effective form of contraception with their sexual partners during the dosing period and for a period of at least 7 months after the end of treatment. 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 during the dosing period until at least 4 months after the last dose of study drug.
- All toxicities from prior therapy have resolved to ≤ grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (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. Note: Patients are not eligible if they are, for reasons other than the age of legal competence to give informed consent, incapable of giving informed consent according to the law of the country concerned.
- Willingness and ability to comply with scheduled visits and study procedures and do not have any contraindications to any of the study procedures.
- For Dose Escalation Phase Cohorts (Phase 1): a. Have histologically- or cytologically-confirmed unresectable or metastatic GIST. b. Have progressed on or are intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib.
You likely can't join if
- 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 OR have received medications that are potent inhibitors of the BCRP (refer to Appendix 5 for a list of these medications) 7 days prior to the first dose of study drug.
- 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.
See the full eligibility criteria
Who can join
- Male or female patient ≥ 18 years of age.
- Female patients of childbearing potential must agree to abstain from heterosexual intercourse or use a highly effective form of contraception with their sexual partners during the dosing period and for a period of at least 7 months after the end of treatment. 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 during the dosing period until at least 4 months after the last dose of study drug.
- All toxicities from prior therapy have resolved to ≤ grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (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. Note: Patients are not eligible if they are, for reasons other than the age of legal competence to give informed consent, incapable of giving informed consent according to the law of the country concerned.
- Willingness and ability to comply with scheduled visits and study procedures and do not have any contraindications to any of the study procedures.
- For Dose Escalation Phase Cohorts (Phase 1): a. Have histologically- or cytologically-confirmed unresectable or metastatic GIST. b. 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): a. Cohort 1: i. Have histologically- or cytologically confirmed unresectable or metastatic GIST. ii. Have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib. b. Cohort 2: i. Have histologically- or cytologically confirmed unresectable or metastatic GIST. ii. 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. c. Cohort 3: i. Have histologically- or cytologically confirmed unresectable or metastatic GIST. ii. Have progressed on or are intolerant to imatinib (including in the adjuvant setting). iii. 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. A tumor sample obtained after most recent prior systemic anticancer therapy is preferred. 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 following criteria: a. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) (<3.0 x ULN for patients with Gilbert syndrome), b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN (or ≤5 × ULN if liver function abnormalities are due to underlying malignancy), and c. Estimated (using Cockcroft-Gault formula or using the method standard for the institution) or measured creatinine clearance ≥60 mL/min.
- Adequate bone marrow function as defined by the following criteria: a. Absolute neutrophil count (ANC) ≥1.5 × 109/L, b. Platelet count ≥75 × 109/L, and c. Hemoglobin ≥9.0 g/dL.
- 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. a. Note: female patients of nonchildbearing potential (postmenopausal; hysterectomy; bilateral salpingectomy; or bilateral oophorectomy) do not require a pregnancy test.
What rules you out
- 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 OR have received medications that are potent inhibitors of the BCRP (refer to Appendix 5 for a list of these medications) 7 days prior to the first dose of study drug.
- 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.
- 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.
- Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to: a. Myocardial infarction (MI) within 6 months prior to the first dose of study drug b. Unstable angina within 6 months prior to first dose of study drug c. Symptomatic congestive heart failure (New York Heart Association classes II-IV) within 6 months prior to first dose of study drug d. Clinically significant, uncontrolled atrial arrhythmia (as determined by the Investigator) e. Any history of ventricular arrhythmia f. Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug g. 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.
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.