A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03563716
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 135
- ECOG Performance Status of 0 or 1
- Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology
- No prior systemic treatment for locally advanced unresectable or metastatic NSCLC
- Tumor PD-L1 expression
- Measurable disease, as defined by RECIST v1.1
- Life expectancy >=12 weeks
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Cancer-Specific Exclusions:
- Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to screening
- History of leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumor-related pain
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome
General Medical Exclusions:
- Pregnant and lactating women
- Significant cardiovascular disease
- Severe infections within 4 weeks prior to randomization
- Major surgical procedure other than for diagnosis within 4 weeks prior to randomization
Treatment-Specific Exclusions:
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of autoimmune disease
- Prior allogeneic bone marrow transplantation or solid organ transplantation
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis
- Administration of a live, attenuated vaccine within 4 weeks prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tiragolumab + Atezolizumab Tiragolumab Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle. Placebo + Atezolizumab Placebo Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle. Placebo + Atezolizumab Atezolizumab Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle. Tiragolumab + Atezolizumab Atezolizumab Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From baseline until a total of 80 PFS events have occurred (up to approximately 11 months) PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Objective Response Rate (ORR) From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months) ORR, defined as a complete response (CR) or partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events Up to 6 years An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Duration of Objective Response (DOR) Up to 6 years DOR, defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Serum Concentrations of Tiragolumab Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days) Serum Concentrations of Atezolizumab Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days) Overall Survival (OS) Up to 6 years OS, defined as the time from randomization to death from any cause.
Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
Trial Locations
- Locations (30)
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Arizona Oncology Associates, PC - HAL
🇺🇸Tempe, Arizona, United States
SCRI Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - NORTH - SCRI - PPDS
🇺🇸Saint Petersburg, Florida, United States
Illinois Cancer Specialists
🇺🇸Arlington Heights, Illinois, United States
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
HCA Midwest Health
🇺🇸Kansas City, Missouri, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Northwest Cancer Specialists - Vancouver
🇺🇸Vancouver, Washington, United States
ICO Paul Papin
🇫🇷Angers, France
Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
🇫🇷Bordeaux, France
Institut De Cancerologie De L'Ouest
🇫🇷Saint Herblain, France
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Institute of Lung Diseases Vojvodina
🇷🇸Sremska Kamenica, Južnobanatski Okrug, Serbia
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Clinical Hospital Center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Hospital Univ Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Complejo Hospitalario Universitario Insular?Materno Infantil
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Madrid, Spain
Centro Medico Quironsalud Sagrado Corazon
🇪🇸Sevilla, Spain
Taipei Medical University ?Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
National Cheng Kung University Hospital
🇨🇳North Dist., Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan, Taiwan