Clinical trial NCT02410512: A Study to Assess the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab (Also Known as MPDL3280A or Anti-PD-L1) in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-04-07
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This Phase Ib, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of the combination of MOXR0916 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy has proven to be ineffective or intolerable or is considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care. Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Life expectancy of at least 12 weeks
* Adequate hematologic and end organ function
* Histologic documentation of locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy is ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is recognized standard of care
* Tumor specimen availability
* Measurable disease according to RECIST v1.1

Exclusion Criteria:

* Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
* Malignancies other than disease under study within 5 years prior to D1 of C1
* Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
* History of leptomeningeal disease
* History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
* History of autoimmune disease
* Positive human immunodeficiency virus test result
* Active hepatitis B, hepatitis C, or tuberculosis
* Severe infection within 4 weeks prior to D1 of C1
* Prior allogeneic bone marrow or solid organ transplantation
* Significant cardiovascular disease
* Known clinically significant liver disease

Primary outcomes:
measure: Number of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted
measure: Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0
timeFrame: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to 3 years)
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD) of MOXR0916
timeFrame: Up to 1 year
measure: Recommended Phase II Dose (RP2D) of MOXR0916
timeFrame: Up to 1 year
measure: Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Number of Cycles Received with MOXR0916
timeFrame: Baseline until treatment discontinuation (up to 3 years)
measure: Dose Intensity of MOXR0916
timeFrame: Baseline until treatment discontinuation (up to 3 years)
measure: Area under the Concentration-Time Curve (AUC) of MOXR0916
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Serum Maximum Observed Concentration (Cmax) of MOXR0916
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Serum Minimum Observed Concentration (Cmin) of MOXR0916
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Clearance (CL) of MOXR0916
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Volume of Distribution at Steady State (Vss) of MOXR0916
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Serum Cmax of Atezolizumab
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Serum Cmin of Atezolizumab
timeFrame: Up to 120 days after the treatment discontinuation visit
measure: Percentage of Participants with Objective Response Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Baseline until disease progression (up to 3 years)
measure: Duration of Objective Response (DOR) Determined Using RECIST v1.1
timeFrame: From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)
measure: Progression-Free Survival (PFS) Determined Using RECIST v1.1
timeFrame: Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)
measure: Percentage of Participants with Objective Response Determined Using Modified RECIST
timeFrame: Baseline until disease progression (up to 3 years)
measure: DOR Determined Using Modified RECIST
timeFrame: From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)
measure: PFS Determined Using Modified RECIST
timeFrame: Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)
measure: Overall Survival (OS)
timeFrame: Baseline until death (up to 3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bisgrove
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: University Of Chicago Medical Center; Section Of Hematology/Oncology
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Can Ins
state: Massachusetts
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: UZ Gent
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System/Severance Hospital
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: