Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

Solid Tumors Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT01988896
• Other study ID #: GP28363
• Secondary ID: 2013-003329-27
• Status: Completed
• Phase: Phase 1
• Start date: December 27, 2013
• Est. completion date: November 4, 2019

Study information

• Verified date: December 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: November 4, 2019
• Est. primary completion date: November 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a fixed dose as specified via IV infusion.
• Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre-East Melbourne	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Canada	CHUM Hôpital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
Germany	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden
Germany	Universitaetsklinikum Freiburg	Freiburg
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Singapore	National University Hospital; Cancer Center	Singapore
United States	Texas Oncology, P.A.	Arlington	Texas
United States	Beth Israel Deaconess Med Ctr; Neurology/MS Center	Boston	Massachusetts
United States	Massachusets General Hospital Clinical Trial Network and Institute	Boston	Massachusetts
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Rocky Mountain Cancer Center - Denver	Denver	Colorado
United States	SCRI-Tennessee Oncology	Nashville	Tennessee
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Sloan Kettering Cancer Center; Pediatric Hematology/Oncology	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
United States	Compass Oncology	Portland	Oregon
United States	University of Washington Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase I: Maximum Tolerated Dose of Cobimetinib		Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Primary	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	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)
Secondary	Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)		Baseline up to approximately 3.5 years
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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 (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])	Baseline up to 3.5 years (detailed time frame is provided in the description)
Secondary	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])
Secondary	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])
Secondary	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])
Secondary	Overall Survival (OS)		Baseline up to death due to any cause (up to approximately 3.5 years)