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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01988896




Registration number
NCT01988896
Ethics application status
Date submitted
14/11/2013
Date registered
20/11/2013
Date last updated
17/12/2019

Titles & IDs
Public title
Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors
Scientific title
A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
2013-003329-27
Secondary ID [2] 0 0
GP28363
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Cobimetinib

Experimental: 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.

Experimental: 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.


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered at a fixed dose as specified via IV infusion.

Treatment: Drugs: Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Primary outcome [2] 0 0
Phase I: Maximum Tolerated Dose of Cobimetinib
Timepoint [2] 0 0
Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Primary outcome [3] 0 0
Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab
Timepoint [3] 0 0
Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Secondary outcome [1] 0 0
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)
Timepoint [2] 0 0
Baseline up to approximately 3.5 years
Secondary outcome [3] 0 0
Serum Maximum Concentration (Cmax) of Atezolizumab
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Serum Minimum Concentration (Cmin) of Atezolizumab
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Plasma Cmax of Cobimetinib
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Plasma Cmin of Cobimetinib
Timepoint [6] 0 0
Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)
Secondary outcome [7] 0 0
Area Under the Concentration-Time Curve (AUC) of Cobimetinib
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [8] 0 0
Baseline up to 3.5 years (detailed time frame is provided in the description)
Secondary outcome [9] 0 0
Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1
Timepoint [9] 0 0
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])
Secondary outcome [10] 0 0
Duration of OR, as Determined by Investigator Using RECIST v1.1
Timepoint [10] 0 0
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])
Secondary outcome [11] 0 0
Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1
Timepoint [11] 0 0
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])
Secondary outcome [12] 0 0
Overall Survival (OS)
Timepoint [12] 0 0
Baseline up to death due to any cause (up to approximately 3.5 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cancer-Specific

- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/11/2019
Sample size
Target
Accrual to date
Final
153
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Germany
State/province [14] 0 0
Freiburg
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01988896
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01988896