Clinical trial NCT02794571: Safety and Pharmacokinetics (PK) of Escalating Doses of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Locally Advanced or Metastatic Tumors
Official title: A Phase Ia/Ib Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Patients With Locally Advanced or Metastatic Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced/Metastatic Tumors
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-09
Enrollment: 518
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of tiragolumab alone or in combination with atezolizumab and/or other anti-cancer therapies in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.


Eligibility criteria: Inclusion Criteria:

* Adults 18 years of age or older
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy at least 12 weeks
* Adequate hematologic and end organ function
* Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
* Confirmed availability of representative tumor specimens
* Measurable disease according to RECIST Version 1.1

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 Day 1 of Cycle 1
* Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
* Leptomeningeal disease
* History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on Screening chest computed tomograph (CT) scan
* History of autoimmune disease
* Positive human immunodeficiency virus (HIV) test
* Active hepatitis B or C, or tuberculosis
* Severe infection within 4 weeks prior to randomization
* Prior allogeneic bone marrow or solid organ transplant
* Significant cardiovascular disease
* Known clinically significant liver disease

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: From Baseline to the end of Cycle 1 (up to 21 days)
measure: Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
timeFrame: From Baseline up to 90 days after last dose of study treatment or until initiation of another systemic anti-cancer therapy (up to approximately 8 years)
measure: Number of Cycles with Tiragolumab
timeFrame: From Baseline to last dose (up to approximately 8 years)
measure: Phase Ia and Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Phase Ib: Percentage of Participants with ADAs to Atezolizumab
timeFrame: Day 1 up to 8 years
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) of Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Maximum Serum Concentration (Cmax) of Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Minimum Serum Concentration (Cmin) of Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Clearance (CL) of Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Volume of Distribution at Steady State (Vss) of Tiragolumab
timeFrame: Day 1 up to 8 years
measure: Cmax of Atezolizumab
timeFrame: Day 1 up to 8 years
measure: Cmin of Atezolizumab
timeFrame: Day 1 up to 8 years
measure: Plasma Concentration of Cisplatin
timeFrame: Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
measure: Plasma Concentration of Carboplatin
timeFrame: Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
measure: Plasma Concentration of Pemetrexed
timeFrame: Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
measure: Plasma Concentration of Paclitaxel
timeFrame: Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
measure: Plasma Concentration of Etoposide
timeFrame: Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
measure: Plasma Concentration of Capecitabine
timeFrame: Pre-dose (5 min) on Day 1 of Cycle 1 and post-dose (2 hours) on Day 1 of Cycle 3 (cycle length 21 days)
measure: Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: From Baseline until disease progression (up to 8 years)
measure: Duration of Objective Response (DOR) According to RECIST Version 1.1
timeFrame: From Baseline until disease progression (up to 8 years)
measure: Progression-Free Survival (PFS) According to RECIST Version 1.1
timeFrame: From Baseline until disease progression (up to 8 years)
measure: Overall survival (OS) According to RECIST Version 1.1
timeFrame: Baseline until death from any cause (up to approximately 8 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre; St Vincents Hospital
state: New South Wales
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonie CLCC Bordeaux
city: Lyon
country: France
facility: Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO L'Hospitalet; Servicio de oncologia medica
state: Barcelona
city: Sant Andreu de La Barca
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de oncología
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: