A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors
20. dubna 2021 aktualizováno: Hoffmann-La Roche
A Phase II, Open-Label, Multicenter, Multicohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients With Solid Tumors
This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).
Přehled studie
Postavení
Postavení
Dokončeno
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Intervenční
Zápis (Aktuální)
Zápis
87
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Kortrijk, Belgie, 8500
- AZ Groeninge
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Seoul, Korejská republika, 03080
- Seoul National University Hospital
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Seoul, Korejská republika, 05505
- Asan Medical Center
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Seoul, Korejská republika, (0)6351
- Samsung Medical Center
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Seoul, Korejská republika, 120-752
- Yonsei Cancer Center
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Budapest, Maďarsko, 1122
- Orszagos Onkologiai Intezet
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Debrecen, Maďarsko, 4032
- Debreceni Egyetem Klinikai Kozpont
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Nyíregyháza, Maďarsko, 4400
- Jósa András Oktatókórház
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Heidelberg, Německo, 69120
- Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
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Tübingen, Německo, 72076
- Universitätsklinikum Tübingen; Klinik für Urologie
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London, Spojené království, EC1A 7BE
- Barts & London School of Med; Medical Oncology
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London, Spojené království, SW3 6JJ
- Royal Marsden Hospital - Fulham
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London, Spojené království, SW7 3RP
- The Royal Marsden
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District of Columbia
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Washington, District of Columbia, Spojené státy, 20007
- Georgetown University Medical Center
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Kansas
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Kansas City, Kansas, Spojené státy, 66209
- Kansas City - Menorah Medical Center
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New York
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Commack, New York, Spojené státy, 11725
- Memorial Sloan-Kettering Cancer Center
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New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering - Basking Ridge
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Tennessee
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Nashville, Tennessee, Spojené státy, 37203
- Sarah Cannon Research Institute
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
General Inclusion Criteria:
- Age ≥18 years
- Ability to comply with the study protocol, in the investigator's judgment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Life expectancy ≥3 months, as determined by the investigator
- Adequate hematologic and end-organ function
Cancer-Related Inclusion Criteria:
- Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.1.
- Availability to provide a representative tumor specimen biopsy
- Evidence of tumor progression on or after the last treatment regimen received and within 6 months prior to study enrollment
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab and within 3 months after the last dose of cobimetinib
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 3 months after the last dose of cobimetinib
Exclusion Criteria:
General Exclusion Criteria:
- Inability to swallow medications
- Malabsorption condition that would alter the absorption of orally administered medications
- Poor peripheral venous access
- Prior treatment with cobimetinib or a MEK inhibitor
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with investigational therapy within 14 days prior to initiation of study treatment
- Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks prior to initiation of study treatment
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, or any component of the cobimetinib formulation
- History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
- Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
- Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L], calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Active or untreated central nervous system (CNS) metastases
- Pregnancy or breastfeeding, or intending to become pregnant during the study
Exclusion Criteria based on Organ Function or Medical History
Cardiovascular
Patients who meet the following cardiovascular exclusion criterion will be excluded from study entry:
- Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or <50%, whichever is lower
Infections Patients who meet any of the following infection exclusion criteria will be excluded from study entry:
- Positive human immunodeficiency virus (HIV) test at screening
- Active hepatitis B virus (HBV) infection (chronic or acute)
- Active hepatitis C virus (HCV) infection
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
7
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: Cohort 1 - SCCHN - Treatment Naive
In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
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Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 2 - UC - Treatment Naive
In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
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Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 3 - RCC - Treatment Naive
In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
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Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 4 - SCCHN - Previous Treatment Exposure
In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
|
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 5 - UC - Previous Treatment Exposure
In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
|
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 6 - RCC - Previous Treatment Exposure
In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
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Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Ostatní jména:
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Experimentální: Cohort 7 - Biopsy Cohort
In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle.
The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1.
Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.
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Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.
Ostatní jména:
Only for participants in cohort 7, the first dose of atezolizumab of 840 mg will be given by IV infusion on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Objective Response Rate (ORR)
Časové okno: Up to approximately 31 months
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Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
CR was defined as disappearance of all lesions.
PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.
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Up to approximately 31 months
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Overall Survival (OS)
Časové okno: Up to approximately 31 months
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Overall survival was defined as the time from enrollment to death from any cause.
The median for OS is Kaplan-Meier estimate.
95% CI for median was computed using the method of Brookmeyer and Crowley.
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Up to approximately 31 months
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Progression-Free Survival (PFS)
Časové okno: Up to approximately 31 months
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PFS was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator(s), using RECIST v1.1, or to death from any cause, whichever occurs first.
Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
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Up to approximately 31 months
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Duration of Response (DOR)
Časové okno: Up to approximately 22 months
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DOR was defined as the time from the first occurrence of a documented, confirmed objective response to disease progression as determined by the investigator, using RECIST v1.1, or to death from any cause, whichever occurs first.
Objective response was defined as a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart.
CR was defined as disappearance of all lesions.
PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.
Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Presented here is median DOR at the time of primary analysis.
The median for the duration of response is Kaplan-Meier estimate.
95% CI for median was computed using the method of Brookmeyer and Crowley.
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Up to approximately 22 months
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Disease Control Rate (DCR)
Časové okno: At 16 weeks
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DCR was defined as the percentage of participants with a complete response (CR), a partial response (PR), or stable disease at 16 weeks as determined by the investigator using RECIST v1.1.
CR was defined as disappearance of all lesions.
PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.
Stable disease was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression.
Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
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At 16 weeks
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Number of Participants With Adverse Events
Časové okno: Up to approximately 31 months
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An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Preexisting conditions which worsen during a study are also considered as adverse events.
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Up to approximately 31 months
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Maximum Plasma Concentration (Cmax) of Cobimetinib
Časové okno: Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose
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Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
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Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose
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Minimum Plasma Concentration (Cmin) of Cobimetinib
Časové okno: Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose
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Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
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Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose
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Maximum Serum Concentration (Cmax) of Atezolizumab
Časové okno: 30 minutes following end of atezolizumab infusion on Day 15 of Cycle 3 (each cycle is 28 days)
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Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
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30 minutes following end of atezolizumab infusion on Day 15 of Cycle 3 (each cycle is 28 days)
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Minimum Serum Concentration (Cmin) of Atezolizumab
Časové okno: Prior to atezolizumab infusion on Day 1 of Cycles (each cycle is 28 days) 2, 4, 8, 12, and 16, Day 15 of Cycle 3
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Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
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Prior to atezolizumab infusion on Day 1 of Cycles (each cycle is 28 days) 2, 4, 8, 12, and 16, Day 15 of Cycle 3
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Number of Participants With Anti-drug Antibodies (ADAs)
Časové okno: Day 1 of Cycles (each cycle is 28 days) 1, 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion (up to approximately 31 months)
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Participants were considered to be ADA positive if they were missing data at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥0.60-titer units) than the titer of the baseline sample (treatment-enhanced ADA response).
Participants were considered to be ADA negative if they were missing data at baseline, had a post-baseline ADA result, and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
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Day 1 of Cycles (each cycle is 28 days) 1, 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion (up to approximately 31 months)
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
23. listopadu 2017
Primární dokončení (Aktuální)
Primární dokončení
25. června 2020
Dokončení studie (Aktuální)
Dokončení studie
25. června 2020
Termíny zápisu do studia
První předloženo
První předloženo
17. srpna 2017
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
24. srpna 2017
První zveřejněno (Aktuální)
První zveřejněno
28. srpna 2017
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
11. května 2021
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
20. dubna 2021
Naposledy ověřeno
Naposledy ověřeno
1. dubna 2021
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- WO39760
- 2017-000794-37 (Číslo EudraCT)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ano
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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