A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03563716
• Other study ID #: GO40290
• Secondary ID: 2018-000280-81
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 10, 2018
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: March 31, 2025
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab
Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.
• Tiragolumab
Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
• Placebo
Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux
France	Centre Georges François Leclerc; Service Pharmacie, Bp 77980	Dijon
France	Hopital Nord AP-HM; Service Clinique des bronches allergies et sommeil	Marseille
France	Institut De Cancerologie De L'Ouest; Medical Oncology	Saint Herblain
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Hospital Center Bezanijska Kosa; Physical Medicine and Rehabilitation	Beograd-zemun
Serbia	Institute of Lung Diseases Vojvodina	Sremska Kamenica
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Univ Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Complejo Hospitalario Universitario Insular?Materno Infantil	Las Palmas de Gran Canaria	LAS Palmas
Spain	Clinica Universitaria Navarra (Madrid)	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario de Malaga ? Hospital General; Servicio de Neurologia	Malaga
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Centro Medico Quironsalud Sagrado Corazon	Sevilla
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Taiwan	Taipei Medical University ?Shuang Ho Hospital	New Taipei City
Taiwan	National Cheng Kung University Hospital; Internal Medicine	North Dist.
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	HCA Midwest Health	Kansas City	Missouri
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Illinois Cancer Care	Peoria	Illinois
United States	SCRI Florida Cancer Specialists North; Research Office North Region.	Saint Petersburg	Florida
United States	Arizona Oncology Associates, PC - HAL	Tempe	Arizona
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Serbia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	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.	From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)
Primary	Progression Free Survival (PFS)	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).	From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
Secondary	Duration of Objective Response (DOR)	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).	Up to 6 years
Secondary	Overall Survival (OS)	OS, defined as the time from randomization to death from any cause.	Up to 6 years
Secondary	Percentage of Participants With Adverse Events	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.	Up to 6 years
Secondary	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)
Secondary	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)
Secondary	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)