A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors
2021년 4월 20일 업데이트: 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).
연구 개요
연구 유형
중재적
등록 (실제)
87
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Seoul, 대한민국, 03080
- Seoul National University Hospital
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Seoul, 대한민국, 05505
- Asan Medical Center
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Seoul, 대한민국, (0)6351
- Samsung Medical Center
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Seoul, 대한민국, 120-752
- Yonsei Cancer Center
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Heidelberg, 독일, 69120
- Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
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Tübingen, 독일, 72076
- Universitätsklinikum Tübingen; Klinik für Urologie
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District of Columbia
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Washington, District of Columbia, 미국, 20007
- Georgetown University Medical Center
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Kansas
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Kansas City, Kansas, 미국, 66209
- Kansas City - Menorah Medical Center
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New York
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Commack, New York, 미국, 11725
- Memorial Sloan-Kettering Cancer Center
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New York, New York, 미국, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, 미국, 10065
- Memorial Sloan Kettering - Basking Ridge
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Tennessee
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Nashville, Tennessee, 미국, 37203
- Sarah Cannon Research Institute
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Kortrijk, 벨기에, 8500
- AZ Groeninge
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London, 영국, EC1A 7BE
- Barts & London School of Med; Medical Oncology
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London, 영국, SW3 6JJ
- Royal Marsden Hospital - Fulham
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London, 영국, SW7 3RP
- The Royal Marsden
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Budapest, 헝가리, 1122
- Orszagos Onkologiai Intezet
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Debrecen, 헝가리, 4032
- Debreceni Egyetem Klinikai Kozpont
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Nyíregyháza, 헝가리, 4400
- Jósa András Oktatókórház
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
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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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
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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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Objective Response Rate (ORR)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Overall Survival (OS)
기간: 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)
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2017년 11월 23일
기본 완료 (실제)
2020년 6월 25일
연구 완료 (실제)
2020년 6월 25일
연구 등록 날짜
최초 제출
2017년 8월 17일
QC 기준을 충족하는 최초 제출
2017년 8월 24일
처음 게시됨 (실제)
2017년 8월 28일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2021년 5월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2021년 4월 20일
마지막으로 확인됨
2021년 4월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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