Description:
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.
Title
- Brief Title: Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors
- Official Title: A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
GP28363
- SECONDARY ID:
2013-003329-27
- NCT ID:
NCT01988896
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Atezolizumab | MPDL3280 | Dose-Escalation: Cobimetinib, Atezolizumab |
| Cobimetinib | GDC-0973 | Dose-Escalation: Cobimetinib, Atezolizumab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose-Escalation: Cobimetinib, Atezolizumab | Experimental | Participants will receive single dose of 800 milligrams (mg) of atezolizumab IV infusion on Day 1, 15 and 29 of Cycle 1 (cycle length=42 days [14-day run-in period + 28-day concomitant dosing period]), thereafter with atezolizumab IV dosing every 2 weeks (q2w) in all subsequent treatment cycles (28 days each). Combination with cobimetinib will begin on Cycle 1 Day 15 and will be given at increasing dose levels during Stage 1. During Stage 1, cobimetinib will be administered once daily (QD) orally for 21 consecutive days out of 28 days (21/7 dosing schedule) at a starting dose of 20 mg with escalation of 20 mg until the maximum tolerated dose (MTD; not more than 60 mg) for the two-drug combination. | |
| Dose-Expansion: Cobimetinib, Atezolizumab | Experimental | Participants will receive single dose of 800 mg of atezolizumab IV infusion q2w in all subsequent treatment cycles (28 days each). Participants will receive cobimetinib at the selected recommended RP2D on Days 1-14 of each 28-day cycle during Stage 2. | |
Eligibility Criteria
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 Exclusion Criteria:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3
weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 28 days prior to enrollment
- Known active or untreated central nervous system (CNS) metastases
- Leptomeningeal disease
- Uncontrolled tumor-related pain or uncontrolled pleural effusion, pericardial
effusion, or ascites requiring recurrent (once monthly or more frequently) drainage
procedures
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy or denosumab
General Medical Exclusion Criteria:
- Pregnant and lactating women
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cell or
any component of the atezolizumab formulation
- History of autoimmune disease
- Participants with prior allogeneic stem cell or solid organ transplantation
- Positive test for human immunodeficiency virus (HIV)
- Participants with active hepatitis B, hepatitis C, or tuberculosis
- Severe infections within 4 weeks prior to Cycle 1 Day 1
- Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1
- Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
- Significant cardiovascular disease
- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day
1 or anticipation of need for a major surgical procedure during the course of the
study
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
Exclusion Criteria Unique to Cobimetinib:
- History of prior significant toxicity from another mitogen-activated protein kinase
(MEK) pathway inhibitor requiring discontinuation of treatment
- Allergy or hypersensitivity to components of the cobimetinib formulations
- History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>)
450 milliseconds at screening
- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
(LLN) or below 50%, whichever is lower, as determined by echocardiogram or Multi Gated
Acquisition Scan (MUGA) scan
- History of or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment, central serous
chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular
degeneration
- History of malabsorption syndrome or other condition that would interfere with enteral
absorption
Exclusion Criteria Related to Medications:
- Prior treatment with clusters of differentiation (CD) 137 agonists or immune
checkpoint blockade therapies, systemic immunostimulatory agents, or systemic
immunosuppressive medications
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs) |
| Time Frame: | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) |
| Time Frame: | Baseline up to approximately 3.5 years |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Maximum Concentration (Cmax) of Atezolizumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Minimum Concentration (Cmin) of Atezolizumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Cmax of Cobimetinib |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Cmin of Cobimetinib |
| Time Frame: | Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Area Under the Concentration-Time Curve (AUC) of Cobimetinib |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
| Time Frame: | Baseline up to 3.5 years (detailed time frame is provided in the description) |
| Safety Issue: | |
| 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]) |
| Measure: | Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1 |
| Time Frame: | 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]) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of OR, as Determined by Investigator Using RECIST v1.1 |
| Time Frame: | 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]) |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1 |
| Time Frame: | 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]) |
| Safety Issue: | |
| Description: | |
| Measure: | Overall Survival (OS) |
| Time Frame: | Baseline up to death due to any cause (up to approximately 3.5 years) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
December 17, 2019
