Исследование FiH по изучению безопасности, фармакокинетики и эффективности NaPi2b ADC TUB-040 у пациентов с ПРОК или р/р аденокарциномой НМРЛ (NAPISTAR1-01)
Первое исследование фазы I/IIa по повышению дозы и оптимизации у человека для изучения безопасности, переносимости, ФК и эффективности NaPi2b ADC TUB-040 у пациентов с платинорезистентным раком яичников высокой степени злокачественности (PROC) или р/р Аденокарцинома немелкоклеточного рака легких (НМРЛ)
The goal of this clinical study is to learn more about the study drug, TUB-040, including its safety, tolerability, pharmacokinetics, and preliminary efficacy, and to determine the best dose of TUB-040 in participants with ovarian cancer or non-small cell lung cancer (NSCLC).
The primary objectives of this study are:
Phase 1: To determine the safety and tolerability of TUB-040 and determine the maximum tolerated dose (MTD) or the identified dose for optimization (IDO).
Phase 2a: To assess safety of TUB-040, the preliminary efficacy of TUB-040, and to identify the recommended phase II dose (RP2D) for further development of TUB-040 .
Phase 2b: To determine the efficacy of TUB-040 in patients with PROC.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
- Фаза 1
Контакты и местонахождение
Контакты исследования
- Имя: Gilead Clinical Study Information Center
- Номер телефона: 1-833-445-3230 (GILEAD-0)
- Электронная почта: GileadClinicalTrials@gilead.com
Места учебы
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Leuven, Бельгия, 3000
- Рекрутинг
- UZ Leuven - PPDS
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Berlin, Германия, 13353
- Рекрутинг
- Charité- Universitaetsmedizin Berlin
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Cologne, Германия, 50937
- Рекрутинг
- University Hospital of Cologne
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Madrid, Испания, 28027
- Рекрутинг
- Clínica Universidad de Navarra - Madrid
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Madrid, Испания, 28223
- Рекрутинг
- NEXT Madrid, University Hospital Quironsalud Madrid
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Cluj-Napoca, Румыния, 40015
- Рекрутинг
- ARENSIA Exploratory Medicine, LLC
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London, Соединенное Королевство, SE1 9RT
- Активный, не рекрутирующий
- Guy's Hospital
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Alabama
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Birmingham, Alabama, Соединенные Штаты, 35294
- Рекрутинг
- University of Alabama at Birmingham
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Georgia
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Atlanta, Georgia, Соединенные Штаты, 30322
- Рекрутинг
- Winship Cancer Institute Emory University
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02215
- Рекрутинг
- Dana Farber Cancer Institute (DFCI)
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New Jersey
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East Brunswick, New Jersey, Соединенные Штаты, 08816
- Рекрутинг
- START New Jersey (Astera Cancer Center)
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New York
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New York, New York, Соединенные Штаты, 10011
- Рекрутинг
- Mount Sinai
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Ohio
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Cincinnati, Ohio, Соединенные Штаты, 45219
- Рекрутинг
- The Christ Hospital Physicians - Mt. Auburn
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Columbus, Ohio, Соединенные Штаты, 43210
- Рекрутинг
- Ohio State University CRS
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Oklahoma
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Oklahoma City, Oklahoma, Соединенные Штаты, 73104
- Рекрутинг
- Stephenson Cancer Center
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Oregon
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Medford, Oregon, Соединенные Штаты, 97504
- Рекрутинг
- Asante Rogue Region al Medical Center
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Texas
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Fort Worth, Texas, Соединенные Штаты, 76104
- Рекрутинг
- START Dallas Fort Worth
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Irving, Texas, Соединенные Штаты, 75039
- Рекрутинг
- NEXT Oncology Dallas
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Utah
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West Valley City, Utah, Соединенные Штаты, 84119
- Рекрутинг
- START Mountain Region
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Virginia
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Fairfax, Virginia, Соединенные Штаты, 22031
- Рекрутинг
- NEXT Virginia
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Kyiv, Украина, 01135
- Активный, не рекрутирующий
- ARENSIA Exploratory Medicine, LLC
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Key Inclusion Criteria (for all phases)
- Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
- Disease not amenable to curative intent treatment.
- Individuals have exhausted the standard of care treatment (SoC) with expected survival benefit and are not denied SoC with expected survival benefit by participating in the trial.
- Individuals with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
- Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
- Individuals must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
- Individuals must be willing to undergo a non-contrast high resolution computed tomography (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
- Adequate organ function
- Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤grade 1 (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic grade 2 peripheral sensory neuropathy after prior taxane therapy or anticancer treatment such as but not limited to immune oncology therapy (IOs)).
- Individuals of childbearing potential (FCBP) who are sexually active with a non-sterilized partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions until the end of exposure, plus 5 half-lives and 6 months add-on in the case of individuals assigned female at birth.
- In the opinion of the investigator, the individual must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
- The individual must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
- The individual must be willing to sign and date the informed consent form (ICF)
Key Exclusion Criteria (for all phases)
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The individual is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
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History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
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Individuals are not allowed to participate in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives of any investigational pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices.
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Individuals with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.
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Prior radiotherapy <2 weeks from trial inclusion.
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Major surgery within 21 days prior to signing the ICF, unless the individual is recovered at that time.
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Has a history of non-infectious interstitial lung disease/pneumonitis (ILD)/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
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Has an oxygen saturation of <93% on room air at rest.
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Has a QTcF >470 ms
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History of nephrotic syndrome
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Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
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Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the individual to the development of complications from the administration of protocol therapy.
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History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
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Documented other concurrent non-malignant comorbidities such as unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV).
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Any anti-tumor chemotherapy, systemic anti-cancer therapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticoid therapy.
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Concurrent use of strong inhibitors or strong inducers of CYP3A4
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Live vaccines within 30 days prior to study entry.
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Individuals with acute or chronic infections such as:
- Individuals who are HBsAg positive are eligible if they have received Hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.
- Individuals with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
- HIV infected individuals must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
- Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
- History of severe and recurrent infections per INV judgment.
- History of progressive multifocal leukoencephalopathy
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Последовательное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: Phase 1: Cohort 1: Dose Escalation in Platinum Resistant Ovarian Cancer (PROC)
Participants will receive escalating doses of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Экспериментальный: Phase 1: Cohort 2: Dose Escalation in R/R NSCLC of the adenocarcinoma subtype
Participants will receive escalating doses of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Экспериментальный: Phase 1: Cohort 3: PROC, Combination with Bevacizumab (BEV)
Participants will receive escalating doses of TUB-040 combined with BEV every 3 weeks until the disease progresses or the patient has to stop due to side effects. |
Administered IV
Другие имена:
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Экспериментальный: Phase 2a: Dose Optimization in PROC
Participants will receive two different dose levels of TUB-040 every 3 weeks until the disease progresses or the patient has to stop due to side effects. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
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Экспериментальный: Phase 2b: Dose Expansion in PROC
Patients will receive TUB-040 at the safe dose established during dose escalation until disease progression or unacceptable toxicity. |
Administered intravenous (IV) on day 1 of each 21-day treatment cycle |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
Временное ограничение: First dose date up to 30 days post last dose (Up to 3 years)
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First dose date up to 30 days post last dose (Up to 3 years)
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Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)
Временное ограничение: First dose up to 21 days
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First dose up to 21 days
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Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
Временное ограничение: Up to 3 years
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ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by BICR. |
Up to 3 years
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Временное ограничение: First dose date up to 30 days post last dose (Up to 3 years)
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First dose date up to 30 days post last dose (Up to 3 years)
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Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments
Временное ограничение: From enrollment until 30 days after last study drug
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From enrollment until 30 days after last study drug
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Phase 2a & 2b: Percentage of Participants Experiencing TEAEs
Временное ограничение: First dose date up to 30 days post last dose date (Up to 3 years)
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First dose date up to 30 days post last dose date (Up to 3 years)
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Phase 2a & 2b: Duration of Response (DOR) by BICR
Временное ограничение: Up to 3 years
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DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by BICR. |
Up to 3 years
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Phase 1, 2a & 2b: ORR by INV
Временное ограничение: Up to 3 years
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ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by Investigator (INV). |
Up to 3 years
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Phase 1, 2a & 2b: DOR by INV
Временное ограничение: Up to 3 years
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DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by INV. |
Up to 3 years
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Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV
Временное ограничение: Up to 3 years
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PFS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by INV. |
Up to 3 years
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Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV
Временное ограничение: Up to 3 years
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DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by INV. |
Up to 3 years
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Phase 2a & 2b: Progression-Free Survival (PFS) by BICR
Временное ограничение: Up to 3 years
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PFS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by BICR. |
Up to 3 years
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Phase 2a & 2b: Disease Control Rate (DCR) by BICR
Временное ограничение: Up to 3 years
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DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by BICR. |
Up to 3 years
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Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities
Временное ограничение: Up to 3 years
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Up to 3 years
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Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total Monoclonal Antibody (mAb), and Free Exatecan: Cmax
Временное ограничение: Up to 3 years
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Cmax is defined as the maximum observed drug concentration. |
Up to 3 years
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Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin
Временное ограничение: Up to 3 years
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The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived). |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax
Временное ограничение: Up to 3 years
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Tmax is defined as the time (observed time point) of Cmax. |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)
Временное ограничение: Up to 3 years
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AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
Up to 3 years
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Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (t1/2)
Временное ограничение: Up to 3 years
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t1/2 is defined as the terminal elimination half-life at steady state. |
Up to 3 years
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Phase 2a & 2b: Overall Survival (OS)
Временное ограничение: Up to 3 years
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OS is defined as the length of time from first dose until the date of death from any cause. |
Up to 3 years
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Phase 2a & 2b: Cancer Antigen (CA)-125 response according to Gynecological Cancer InterGroup (GCIG)
Временное ограничение: Up to 3 years
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Up to 3 years
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Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Gilead Study Director, Gilead Sciences
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Урогенитальные заболевания
- Генитальные заболевания
- Заболевания эндокринной системы
- Урогенитальные новообразования
- Новообразования по локализации
- Новообразования
- Женские урогенитальные заболевания
- Женские мочеполовые заболевания и осложнения беременности
- Заболевания дыхательных путей
- Заболевания половых органов, Женский
- Легочные заболевания
- Новообразования эндокринных желез
- Новообразования дыхательных путей
- Грудные новообразования
- Новообразования легких
- Заболевания яичников
- Заболевания придатков
- Генитальные Новообразования, Женщины
- Заболевания гонад
- Рак, Бронхогенный
- Бронхиальные новообразования
- Новообразования яичников
- Карцинома немелкоклеточного легкого
- Аминокислоты, пептиды и белки
- Белки
- Антитела, моноклональные, гуманизированные
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Бевацизумаб
Другие идентификационные номера исследования
- NAPISTAR 1-01
- 2024-511074-80 (Номер EudraCT)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .