E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Solid tumors are masses of abnormal tissue growth that originate in organs or soft tissues and do not include fluid areas and cysts |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of cobimetinib plus atezolizumab by objective response rate (ORR) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of cobimetinib plus atezolizumab by OS, PFS, DOR and DCR
To evaluate the safety of cobimetinib plus atezolizumab
To characterize cobimetinib and atezolizumab pharmacokinetics
To evaluate the immune response to atezolizumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Overall survival
2. Progression-free survival
3. Duration of response (DOR)
4. Disease control rate (DCR)
5. Occurrence and severity of adverse events, with severity determined according to the NCI CTCAE v4.0
6. Change from baseline in targeted vital signs
7. Change from baseline in targeted clinical laboratory test results
8. Plasma concentration of cobimetinib at specified timepoints
9. Serum concentration of atezolizumab at specified timepoints
10. Presence of ADAs during the study relative to the presence of ADAs at baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-7. Up to 3 years
8. Day 15 of Cycle 3
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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Germany |
Hungary |
Korea, Republic of |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will end when all patients enrolled have been followed until death, withdrawal of consent, loss to follow-up, or the Sponsor decides to end the trial, whichever occurs first. Patients may continue study treatment until the development of progressive
disease, unacceptable toxicity, and/or withdrawal of consent. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |