2025-524934-24-00招募中3 期
A Phase 3, Randomized, Multicenter, Open-Label Study of Velzatinib (GSK6042981) versus Imatinib in Participants with Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 302
- 试验地点
- 95
- 主要终点
- PFS, defined as time from the date of randomization to the date of disease progression, as assessed by BICR or death due to any cause, whichever occurs first.
研究概览
简要总结
To evaluate the efficacy (clinical activity) of velzatinib compared with imatinib in previously untreated participants with metastatic and/or unresectable GIST, as evidenced by PFS
研究设计
- 分配方式
- Na
- 主要目的
- Follow up
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
- •Has histologically or cytologically confirmed GIST that is metastatic and/or surgically unresectable.
- •Has not received prior systemic therapy for their metastatic and/or surgically unresectable GIST. NOTE: Participants may be enrolled if they received surgery for localized GIST, with or without neoadjuvant or adjuvant imatinib, and then recur with metastatic or localized unresectable disease and at least 6 months have passed since the last dose of imatinib, prior to the diagnosis of metastatic or surgically unresectable GIST.
- •Tumor tissue must be provided to the central laboratory. Tumor tissues may be archival (preferred) or obtained from a fresh biopsy acquired for standard of care (biopsies must be collected before randomization). Tissue samples can be submitted either before or after randomization. Tissue requirements will be detailed in the Laboratory Manual.
- •Participants must have ≥1 target lesion (TL)
- •Is willing to use adequate contraception [male and/or female participants]. o Contraceptive use by [male and/or female participants] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: • Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 30 days after the last dose of velzatinib and 30 days after the last dose of imatinib or as specified in local appendices, whichever is longer: • Refrain from donating fresh unwashed semen. PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), including any activity of passage of ejaculate to another person and agree to remain abstinent. OR • Must agree to use contraception/barrier as detailed below: • Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a partner who can become pregnant and is not currently pregnant. Female participants: • A female participant is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies: • Is a PONCBP as defined in the protocol. OR • Is a POCBP and using an acceptable contraceptive method, as described in the protocol, 30 days, prior to and during the study intervention period and for at least 30 days after the last dose of study intervention (for participants receiving velzatinib), or at least 15 days after the last dose of treatment (for participants receiving imatinib), or as specified in local appendices, whichever is longer. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). • A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 30 days before the first dose of study intervention (see Section of Pregnancy testing in full protocol). • If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after the study intervention are located in pregnancy Section of the protocol. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a person with an early undetected pregnancy.
- •Is capable of giving signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Has an ECOG performance status of ≤
- •Has adequate organ function as defined in Table
- •Note: A complete blood count test should be obtained without packed red blood cell transfusion or receipt of erythropoietin within 2 weeks of obtaining the sample. Table 5 Definitions for adequate organ function System Laboratory Value Hematologic ANC ≥1500/μL (≥1.5 x 10e9/L). Criteria must be met without erythropoietin dependency and without pRBC transfusion within previous 2 weeks. Platelets ≥90,000/μL (≥90 x 10e9/L). Criteria must be met without erythropoietin dependency and without pRBC transfusion within previous 2 weeks. Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be met without erythropoietin dependency and without pRBC transfusion within previous 2 weeks. Renal eGFR ≥30 mL/min (using CKD-EPI 2021 [Inker, 2021] formula or method standard for the institution). eGFR to be calculated using the CKD-EPI formula [Inker, 2021], or applicable country-specific formula and indexed to the individual body surface area. Coagulation INR or PT ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. aPTT ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
排除标准
- •Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of metastatic disease.
- •Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant’s safety, obtainment of informed consent, or compliance to the study procedures.
- •Has received radiotherapy within 14 days prior to first dose of study treatment.
- •Has received any live vaccine within 30 days of randomization. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live. If a COVID-19 vaccine is administered at any time, the date of COVID-19 vaccination must be entered in the eCRF.
- •Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including G-CSF, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before randomization.
- •Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of medical research before signing ICF.
- •Has a positive drug/alcohol screening assessment.
- •Has a known HIV infection AND meets at least one of the following criteria: • Has documented evidence of plasma HIV-1 RNA ≥50 c/mL within 3 months prior to or at screening. In the 3 to 12 months prior to screening, plasma HIV 1 RNA levels consistently <50 c/mL are required for enrollment; if multiple instances of plasma HIV-1 RNA values ≥50 c/mL occurred in the 3 to 12 months prior to screening, the participant is not eligible for enrollment unless, per the investigator’s assessment, the elevations were neither persistent nor associated with antiretroviral resistance; OR • Has not had CD4 cell counts measured in the past 12 months (i.e., at least two separate measurements taken a minimum of 28 days apart, one of which must be conducted at screening); OR • Has had any CD4 cell count values ≤200 cells/mm3 in the past 12 months; OR • Has had one or more changes in their combination antiretroviral therapy regimen (except for switches as allowed per details provided in protocol) or has received an antiretroviral therapy regimen that is inconsistent with locally recommended guidelines during the 3 months prior to screening; OR • Has a history of HIV-associated non-Hodgkin lymphoma within 5 years prior to screening or a history of HIV-associated invasive cervical cancer; OR • Has received treatment with an HIV 1 immunotherapeutic vaccine within 90 days of screening. NOTE: Participants with history of CDC Stage 3 disease (also known as AIDS defining disease [Centers for Disease Control and Prevention, 2014]) are eligible (provided all other applicable criteria are met) if the AIDS-defining disease has been treated and cured or is stable for at least 3 months prior to screening. Cutaneous Karposi’s Sarcoma not requiring systemic therapy is not exclusionary.
- •Is pregnant or breastfeeding.
- •Is unable to adhere to the protocol defined SoA, including requirements for the Follow-up Period of the study.
- •Has an ALT value >2.5x ULN or (for participants with documented liver metastases/tumor infiltration) has an ALT value >5x ULN
- •Has any clinically significant gastrointestinal abnormalities that may alter absorption, e.g., malabsorption syndrome or major resection of the stomach and/or bowels.
- •Has a total bilirubin value >1.5x ULN. NOTE: Participants with Gilbert’s syndrome can be included with a total bilirubin value >1.5x ULN, provided direct bilirubin is ≤1.5x ULN and participant otherwise meets entry criteria.
- •Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. NOTE: Stable noncirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones), hepatobiliary involvement of malignancy, or chronic stable HBV infection (in a participant for whom HDV infection has been excluded) or chronic HCV infection is acceptable if the participant otherwise meets entry criteria.
- •Evidence of chronic hepatitis B virus (HBV) infection with detectable viral load despite antiviral therapy with high resistance barrier.
- •12-lead ECG demonstrating mean QTc corrected by Fridericia’s formula >480msec at screening or history of long QT syndrome.. Note: Triplicate ECG to be performed no more than 2 minutes between each ECG if first ECG demonstrates> 470 msec.
- •Has had any major surgery (minor surgical procedures such as central venous catheter placement and tumor needle biopsy are not considered major surgical procedures) within 14 days of the first dose of study treatment or participants who have not fully recovered from surgery.
- •Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant. Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a) transplant was [>100 days] prior to screening, and b) the participant has no active infection(s) at the time of screening.
- •Has known allergy or hypersensitivity to velzatinib or imatinib, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
- •Has a history within 6 months prior of clinically significant or uncontrolled cardiac disease, unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure [NYHA, 1994], or clinically significant arrhythmia not controlled by standard of care therapy, ventricular arrhythmia, cerebrovascular accident or transient ischemic attack and uncontrolled hypertension.
- •Has untreated brain or CNS metastases or brain/CNS metastases that have progressed [e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases]. Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥2 weeks before randomization are not excluded from participation.
- •Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, (excluding e.g., alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy) or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
- •Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant’s safety).
研究组 & 干预措施
Imatinib mesylate, Imatinib mesylate
Comparator
干预措施: Imatinib mesylate (Drug)
结局指标
主要结局
PFS, defined as time from the date of randomization to the date of disease progression, as assessed by BICR or death due to any cause, whichever occurs first.
PFS, defined as time from the date of randomization to the date of disease progression, as assessed by BICR or death due to any cause, whichever occurs first.
次要结局
- Confirmed ORR , as assessed by BICR; ORR is defined as the percentage of participants with a confirmed CR or PR.
- OS, defined as the time from the date of randomization to the date of death due to any cause.
- Confirmed ORR by the investigator. PFS2, by local assessment. PFS assessed by the investigator. TTR by BICR and by the investigator. DOR by BICR and by the investigator.
- TSST is defined as the time from the date of randomization to the earliest date of second subsequent therapy or death due to any cause.
- Incidence and severity of TEAEs and SAEs; dose reductions and interruptions and discontinuation of study treatment due to toxicity. Changes in vital signs, electrocardiograms, and clinical laboratory parameters.
- Plasma concentrations of velzatinib.
- Change from baseline as assessed by the EORTC QLQ-C30 Physical & Role Functioning and HRQoL domains. TTCD in Physical & Role Functioning and HRQoL, defined as the time from the date of randomization to the first confirmed clinically meaningful deterioration on the Physical & Role Functioning & Global Health Status/QoL scales of the EORTC QLQ-C30
- Frequency and severity of symptomatic AEs as measured by the PRO-CTCAE. Level of bother of AEs/tolerability as measured by the FACT-GP5.
研究者
EU GSK Clinical Trials Call Center
Scientific
Glaxosmithkline Research & Development Limited
研究点 (95)
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