Clinical trial NCT03563716: A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase II, Randomized, Blinded, Placebo-Controlled Study of Tiragolumab, An Anti-TIGIT Antibody, In Combination With Atezolizumab In Chemotherapy-Naïve Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-20
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)
measure: Progression Free Survival (PFS)
timeFrame: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
Secondary outcomes:
measure: Duration of Objective Response (DOR)
timeFrame: Up to 6 years
measure: Overall Survival (OS)
timeFrame: Up to 6 years
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 6 years
measure: Serum Concentrations of Tiragolumab
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
measure: Serum Concentrations of Atezolizumab
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
measure: Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Kansas City
country: United States
facility: HCA Midwest Health
state: Missouri
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver
state: Washington
city: Angers
country: France
facility: ICO Paul Papin
city: Bordeaux
country: France
facility: Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
city: Saint Herblain
country: France
facility: Institut De Cancerologie De L'Ouest
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Sremska Kamenica
country: Serbia
facility: Institute of Lung Diseases Vojvodina
state: Južnobanatski Okrug
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Badalona
country: Spain
facility: Hospital Univ Germans Trias i Pujol
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular?Materno Infantil
state: LAS Palmas
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Sevilla
country: Spain
facility: Centro Medico Quironsalud Sagrado Corazon
city: New Taipei City
country: Taiwan
facility: Taipei Medical University ?Shuang Ho Hospital
city: North Dist.
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Cho BC, Abreu DR, Hussein M, Cobo M, Patel AJ, Secen N, Lee KH, Massuti B, Hiret S, Yang JCH, Barlesi F, Lee DH, Ares LP, Hsieh RW, Patil NS, Twomey P, Yang X, Meng R, Johnson ML. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022 Jun;23(6):781-792. doi: 10.1016/S1470-2045(22)00226-1. Epub 2022 May 13.