Solid Tumors
Conditions
Brief summary
This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered at a fixed dose as specified via IV infusion.
DRUGCobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Solid tumor that is metastatic, locally advanced or recurrent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy greater than or equal to (\>/=) 12 weeks * Measurable disease, as defined by RECIST v 1.1 * Adequate hematologic and end organ function * Use of highly effective contraception * Histological tumor tissue specimen * Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer: * Metatastic colorectal cancer * Non-small cell lung cancer * Melanoma
Exclusion criteria
Cancer-Specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase |
| Phase I: Maximum Tolerated Dose of Cobimetinib | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase |
| Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Minimum Concentration (Cmin) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years) | — |
| Plasma Cmax of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | — |
| Plasma Cmin of Cobimetinib | Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | — |
| Area Under the Concentration-Time Curve (AUC) of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | — |
| Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years) | — |
| Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | — |
| Duration of OR, as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | — |
| Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | — |
| Overall Survival (OS) | Baseline up to death due to any cause (up to approximately 3.5 years) | — |
| Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Baseline up to 3.5 years (detailed time frame is provided in the description) | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 \[cycle length=42 days\]; thereafter every 12 weeks until progressive disease \[PD\] or death due to any cause, whichever occurs first \[up to approximately 3.5 years\]) |
| Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) | Baseline up to approximately 3.5 years | — |
| Serum Maximum Concentration (Cmax) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days) | — |
Countries
Australia, Canada, Germany, Singapore, South Korea, United States
Outcome results
None listed