A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors
2021年4月20日 更新者：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).
調査の概要
研究の種類
介入
入学 (実際)
87
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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District of Columbia
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Washington、District of Columbia、アメリカ、20007
- Georgetown University Medical Center
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Kansas
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Kansas City、Kansas、アメリカ、66209
- Kansas City - Menorah Medical Center
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New York
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Commack、New York、アメリカ、11725
- Memorial Sloan-Kettering Cancer Center
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering Cancer Center
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering - Basking Ridge
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- Sarah Cannon Research Institute
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London、イギリス、EC1A 7BE
- Barts & London School of Med; Medical Oncology
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London、イギリス、SW3 6JJ
- Royal Marsden Hospital - Fulham
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London、イギリス、SW7 3RP
- The Royal Marsden
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Heidelberg、ドイツ、69120
- Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
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Tübingen、ドイツ、72076
- Universitätsklinikum Tübingen; Klinik für Urologie
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Budapest、ハンガリー、1122
- Orszagos Onkologiai Intezet
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Debrecen、ハンガリー、4032
- Debreceni Egyetem Klinikai Kozpont
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Nyíregyháza、ハンガリー、4400
- Jósa András Oktatókórház
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Kortrijk、ベルギー、8500
- AZ Groeninge
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Seoul、大韓民国、03080
- Seoul National University Hospital
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Seoul、大韓民国、05505
- Asan Medical Center
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Seoul、大韓民国、(0)6351
- Samsung Medical Center
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Seoul、大韓民国、120-752
- Yonsei Cancer Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
他の名前：
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.
他の名前：
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実験的：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.
他の名前：
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.
他の名前：
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実験的：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.
他の名前：
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.
他の名前：
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実験的：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.
他の名前：
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.
他の名前：
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実験的：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.
他の名前：
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.
他の名前：
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実験的：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.
|
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.
他の名前：
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.
他の名前：
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実験的：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.
他の名前：
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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Objective Response Rate (ORR)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Survival (OS)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
|
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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2017年11月23日
一次修了 (実際)
2020年6月25日
研究の完了 (実際)
2020年6月25日
試験登録日
最初に提出
2017年8月17日
QC基準を満たした最初の提出物
2017年8月24日
最初の投稿 (実際)
2017年8月28日
学習記録の更新
投稿された最後の更新 (実際)
2021年5月11日
QC基準を満たした最後の更新が送信されました
2021年4月20日
最終確認日
2021年4月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
固形腫瘍の臨床試験
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AstraZeneca積極的、募集していないAdv Solid Malig - H&N SCC、ATM Pro / Def NSCLC、胃がん、乳がん、卵巣がんアメリカ, フランス, イギリス, 韓国