A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Solid Tumors
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 153
- Locations
- 21
- Primary Endpoint
- Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
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
Arms & Interventions
Dose-Escalation: Cobimetinib, Atezolizumab
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.
Intervention: Atezolizumab
Dose-Escalation: Cobimetinib, Atezolizumab
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.
Intervention: Cobimetinib
Dose-Expansion: Cobimetinib, Atezolizumab
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.
Intervention: Atezolizumab
Dose-Expansion: Cobimetinib, Atezolizumab
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.
Intervention: Cobimetinib
Outcomes
Primary Outcomes
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
Phase I: Maximum Tolerated Dose of Cobimetinib
Time Frame: 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
Time Frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Secondary Outcomes
- Overall Survival (OS)(Baseline up to death due to any cause (up to approximately 3.5 years))
- 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))
- 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))
- 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))
- Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)(Baseline up to approximately 3.5 years)
- 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 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]))