A Study to Investigate the Efficacy and Safety of Cobimetinib plus Atezolizumab in Patients with Solid Tumors

Phase 1

Conditions: Solid tumors
MedDRA version: 20.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-000794-37-GB

Lead Sponsor: F. Hoffman-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 250

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. For patients with SCCHN or RCC, histologic samples are required. For patients with UC, cytological or histologic samples are acceptable.
- 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. Women must refrain from donating eggs during this same period.
- 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 166
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

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
- For patients in Cohorts 1, 2, and 3 only: 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 or hypersensitivity to any anti–PD-1/PD-L1 therapy
- 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 mmol/L, calcium > 12 mg/dL, or corrected calcium greater than the ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Active or untreated 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 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of cobimetinib plus atezolizumab by objective response rate (ORR);Secondary Objective: To evaluate the efficacy of cobimetinib plus atezolizumab by OS, PFS, DOR and DCR<br>To evaluate the safety of cobimetinib plus atezolizumab<br>To characterize cobimetinib and atezolizumab pharmacokinetics<br>To evaluate the immune response to atezolizumab<br>;Primary end point(s): 1. Objective response;Timepoint(s) of evaluation of this end point: 1. Up to 3 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Overall survival<br>2. Progression-free survival<br>3. Duration of response (DOR)<br>4. Disease control rate (DCR)<br>5. Occurrence and severity of adverse events, with severity determined according to the NCI CTCAE v4.0<br>6. Change from baseline in targeted vital signs<br>7. Change from baseline in targeted clinical laboratory test results<br>8. Plasma concentration of cobimetinib at specified timepoints<br>9. Serum concentration of atezolizumab at specified timepoints<br>10. Presence of ADAs during the study relative to the presence of ADAs at baseline<br>;Timepoint(s) of evaluation of this end point: 1-7. Up to 3 years<br>8. Day 15 of Cycle 3<br>9-10. Day 1 (Cohorts 1-6 only), Day 15 (Cohort 7 only) of Cycle 1; Day 1 of Cycles 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion<br>

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