Clinical trial NCT03264066: A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors
Official title: A Phase II, Open-Label, Multicenter, Multicohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-08-28
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 31 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 31 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 31 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 22 months
measure: Disease Control Rate (DCR)
timeFrame: At 16 weeks
measure: Number of Participants With Adverse Events
timeFrame: Up to approximately 31 months
measure: Maximum Plasma Concentration (Cmax) of Cobimetinib
timeFrame: Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose
measure: Minimum Plasma Concentration (Cmin) of Cobimetinib
timeFrame: Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose
measure: Maximum Serum Concentration (Cmax) of Atezolizumab
timeFrame: 30 minutes following end of atezolizumab infusion on Day 15 of Cycle 3 (each cycle is 28 days)
measure: Minimum Serum Concentration (Cmin) of Atezolizumab
timeFrame: 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
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: 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)
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Kansas City
country: United States
facility: Kansas City - Menorah Medical Center
state: Kansas
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering - Basking Ridge
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Heidelberg
country: Germany
facility: Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen; Klinik für Urologie
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Nyíregyháza
country: Hungary
facility: Jósa András Oktatókórház
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center
city: London
country: United Kingdom
facility: Barts & London School of Med; Medical Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
city: London
country: United Kingdom
facility: The Royal Marsden
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: