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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03563716
• Collaborator: (none)
• Enrollment: 135
• Locations: 41
• Arms: 2
• Anticipated Duration (Months): 50.7
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Atezolizumab; Drug: Tiragolumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 10, 2018
• Actual Primary Completion Date: Jun 30, 2019
• Anticipated Study Completion Date: Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo + 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.	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.; Other Names: Tecentriq ; Drug: Placebo; Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Experimental: Tiragolumab + 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.	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.; Other Names: Tecentriq ; Drug: Tiragolumab; Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: MTIG7192A

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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).

Secondary Outcome Measures

1. Duration of Objective Response (DOR) [Up to 5 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).

2. Overall Survival (OS) [Up to 5 years]

   OS, defined as the time from randomization to death from any cause.

3. Percentage of Participants With Adverse Events [Up to 5 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.

4. 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), at treatment discontinuation visit (up to 5 years).]

5. 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), at treatment discontinuation visit (up to 5 years).]

6. 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), at treatment discontinuation visit (up to 5 years).]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC - HAL	Tempe	Arizona	United States	85284
2	SCRI Florida Cancer Specialists South	Fort Myers	Florida	United States	33916
3	SCRI Florida Cancer Specialists North; Research Office North Region.	Saint Petersburg	Florida	United States	33705
4	Illinois Cancer Specialists	Arlington Heights	Illinois	United States	60005
5	Illinois Cancer Care	Peoria	Illinois	United States	61615
6	University of Kansas Medical Center	Westwood	Kansas	United States	66205
7	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
8	HCA Midwest Health	Kansas City	Missouri	United States	64132
9	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
10	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
11	Northwest Cancer Specialists - Vancouver	Vancouver	Washington	United States	98684
12	ICO Paul Papin; Oncologie Medicale.	Angers		France	49055
13	Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux		France	33076
14	Centre Georges François Leclerc; Service Pharmacie, Bp 77980	Dijon		France	21000
15	Hopital Nord AP-HM; Service Clinique des bronches allergies et sommeil	Marseille		France	13015
16	Institut De Cancerologie De L'Ouest; Medical Oncology	Saint Herblain		France	44115
17	Chungbuk National University Hospital	Cheongju-si		Korea, Republic of	28644
18	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
19	Seoul National University Hospital	Seoul		Korea, Republic of	03080
20	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
21	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
22	Asan Medical Center	Seoul		Korea, Republic of	05505
23	Clinical Center of Serbia	Belgrade		Serbia	11000
24	University Hospital Medical Center Bezanijska kosa	Belgrade		Serbia	11080
25	Institute of Lung Diseases Vojvodina	Sremska Kamenica		Serbia	21204
26	Hospital Univ Germans Trias i Pujol	Badalona	Barcelona	Spain	8916
27	Complejo Hospitalario Universitario Insular-Materno Infantil	Las Palmas de Gran Canaria	LAS Palmas	Spain	35016
28	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid	Spain	28220
29	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra	Spain	31008
30	Hospital General Universitario de Alicante	Alicante		Spain	03010
31	Hospital Universitari Vall d'Hebron; Oncology	Barcelona		Spain	08035
32	Clinica Universitaria Navarra (Madrid)	Madrid		Spain	28036
33	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
34	Hospital Regional Universitario de Malaga - Hospital General; Servicio de Neurologia	Malaga		Spain	29010
35	Centro Medico Quironsalud Sagrado Corazon	Sevilla		Spain	41013
36	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
37	Taipei Medical University -Shuang Ho Hospital	New Taipei City		Taiwan	23561
38	National Cheng Kung University Hospital; Internal Medicine	North Dist.		Taiwan	70403
39	Taipei Veterans General Hospital	Taipei City		Taiwan	112
40	National Taiwan University Hospital	Taipei		Taiwan	10002
41	Chang Gung Memorial Hospital - Linkou	Taoyuan		Taiwan	333

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 6, 2020

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03563716
• Other Study ID Numbers: GO40290; 2018-000280-81
• First Posted: Jun 20, 2018
• Last Update Posted: Jun 1, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Atezolizumab

Study Results

Participant Flow

Recruitment Details	Participants were recruited at study sites in 6 countries.
Pre-assignment Detail	Eligible patients with previously untreated, locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC) were randomized 1:1 to receive either placebo plus atezolizumab or tiragolumab plus atezolizumab.

Arm/Group Title	Placebo + Atezolizumab	Tiragolumab + Atezolizumab
Arm/Group Description	Participants received 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 placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.	Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion 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.
Period Title: Overall Study
STARTED	68	67
COMPLETED	0	0
NOT COMPLETED	68	67

Baseline Characteristics

Arm/Group Title	Placebo + Atezolizumab	Tiragolumab + Atezolizumab	Total
Arm/Group Description	Participants received 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.	Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion 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.	Total of all reporting groups
Overall Participants	68	67	135
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.0 (9.9)	65.8 (10.4)	66.4 (10.1)
Sex: Female, Male (Count of Participants)
Female	20 29.4%	28 41.8%	48 35.6%
Male	48 70.6%	39 58.2%	87 64.4%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	0 0%	1 1.5%	1 0.7%
Not Hispanic or Latino	63 92.6%	60 89.6%	123 91.1%
Not Stated	5 7.4%	4 6%	9 6.7%
Unknown	0 0%	2 3%	2 1.5%
Race/Ethnicity, Customized (Count of Participants)
Asian	23 33.8%	18 26.9%	41 30.4%
White	40 58.8%	42 62.7%	82 60.7%
Multiple	1 1.5%	0 0%	1 0.7%
Unknown	4 5.9%	7 10.4%	11 8.1%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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.
Time Frame	From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all participants randomized in the study.

Arm/Group Title	Placebo + Atezolizumab	Tiragolumab + Atezolizumab
Arm/Group Description	Participants received 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.	Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion 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.
Measure Participants	68	67
Number (95% Confidence Interval) [percentage of participants]	16.2 23.8%	31.3 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Atezolizumab, Tiragolumab + Atezolizumab
	Comments	Stratified analysis based on PD-L1 immunohistochemistry (IHC) 22C3 pharmDx, tumor histology status, and tobacco history.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.57
	Confidence Interval	(2-Sided) 95%; 1.07 to 6.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for odds ratio was constructed using the Wald method.

2. Primary Outcome

Title	Progression Free Survival (PFS)
Description	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).
Time Frame	From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)

Outcome Measure Data

Analysis Population Description

ITT population included all participants randomized in the study.

Arm/Group Title	Placebo + Atezolizumab	Tiragolumab + Atezolizumab
Arm/Group Description	Participants received 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.	Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion 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.
Measure Participants	68	67
Median (95% Confidence Interval) [months]	3.58	5.42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Atezolizumab, Tiragolumab + Atezolizumab
	Comments	Stratified analysis based on PD-L1 IHC 22C3 pharmDx, tumor histology status, and tobacco history.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were estimated by Cox regression.

3. Secondary Outcome

Title	Duration of Objective Response (DOR)
Description	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).
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS, defined as the time from randomization to death from any cause.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Serum Concentrations of Tiragolumab
Time Frame	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Serum Concentrations of Atezolizumab
Time Frame	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Time Frame	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to primary completion date (approximately 11 months)
Adverse Event Reporting Description	The safety population included all participants who received at least one dose of study medication.
Arm/Group Title	Placebo + Atezolizumab		Tiragolumab + Atezolizumab
Arm/Group Description	Participants received 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.		Participants received atezolizumab at a fixed dose of 1200 mg administered by IV infusion 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.
All Cause Mortality
	Placebo + Atezolizumab		Tiragolumab + Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/68 (29.4%)		15/67 (22.4%)
Serious Adverse Events
	Placebo + Atezolizumab		Tiragolumab + Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/68 (35.3%)		23/67 (34.3%)
Cardiac disorders
Atrial fibrillation	0/68 (0%)	0	1/67 (1.5%)	1
Cardio-respiratory arrest	1/68 (1.5%)	1	0/67 (0%)	0
Myocarditis	1/68 (1.5%)	1	0/67 (0%)	0
Tachycardia	1/68 (1.5%)	1	0/67 (0%)	0
Endocrine disorders
Adrenal haemorrhage	1/68 (1.5%)	1	0/67 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/68 (1.5%)	1	0/67 (0%)	0
Colitis	0/68 (0%)	0	1/67 (1.5%)	1
Constipation	0/68 (0%)	0	1/67 (1.5%)	1
General disorders
Asthenia	1/68 (1.5%)	1	0/67 (0%)	0
Multiple organ dysfunction syndrome	1/68 (1.5%)	1	0/67 (0%)	0
Pain	1/68 (1.5%)	1	0/67 (0%)	0
Pyrexia	1/68 (1.5%)	1	1/67 (1.5%)	1
Hepatobiliary disorders
Hepatitis	0/68 (0%)	0	1/67 (1.5%)	1
Immune-mediated hepatitis	1/68 (1.5%)	1	0/67 (0%)	0
Infections and infestations
Cytomegalovirus colitis	1/68 (1.5%)	1	0/67 (0%)	0
Epstein-Barr virus infection	0/68 (0%)	0	1/67 (1.5%)	1
Influenza	0/68 (0%)	0	2/67 (3%)	2
Lung infection	1/68 (1.5%)	1	0/67 (0%)	0
Pleural infection bacterial	0/68 (0%)	0	1/67 (1.5%)	1
Pneumonia	4/68 (5.9%)	5	5/67 (7.5%)	5
Respiratory tract infection	1/68 (1.5%)	1	0/67 (0%)	0
Skin infection	0/68 (0%)	0	1/67 (1.5%)	1
Upper respiratory tract infection	1/68 (1.5%)	1	0/67 (0%)	0
Urinary tract infection	0/68 (0%)	0	1/67 (1.5%)	1
Injury, poisoning and procedural complications
Infusion related reaction	0/68 (0%)	0	1/67 (1.5%)	1
Investigations
Alanine aminotransferase increased	1/68 (1.5%)	1	0/67 (0%)	0
Aspartate aminotransferase increased	1/68 (1.5%)	1	0/67 (0%)	0
Lipase increased	0/68 (0%)	0	1/67 (1.5%)	1
Metabolism and nutrition disorders
Decreased appetite	1/68 (1.5%)	1	0/67 (0%)	0
Hyperglycaemia	1/68 (1.5%)	1	0/67 (0%)	0
Hyponatraemia	0/68 (0%)	0	1/67 (1.5%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/68 (1.5%)	1	0/67 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pericardial effusion malignant	0/68 (0%)	0	1/67 (1.5%)	1
Nervous system disorders
Cerebrovascular accident	1/68 (1.5%)	2	0/67 (0%)	0
Encephalopathy	0/68 (0%)	0	1/67 (1.5%)	1
Neurotoxicity	1/68 (1.5%)	1	0/67 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/68 (1.5%)	1	0/67 (0%)	0
Autoimmune nephritis	0/68 (0%)	0	1/67 (1.5%)	1
Hydronephrosis	1/68 (1.5%)	1	0/67 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/68 (1.5%)	1	0/67 (0%)	0
Dyspnoea	1/68 (1.5%)	1	1/67 (1.5%)	1
Haemoptysis	0/68 (0%)	0	1/67 (1.5%)	1
Interstitial lung disease	1/68 (1.5%)	1	0/67 (0%)	0
Pleural effusion	0/68 (0%)	0	4/67 (6%)	4
Pneumonia aspiration	1/68 (1.5%)	1	0/67 (0%)	0
Pneumothorax	0/68 (0%)	0	1/67 (1.5%)	1
Pulmonary embolism	2/68 (2.9%)	2	0/67 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/68 (1.5%)	1	0/67 (0%)	0
Vascular disorders
Pelvic venous thrombosis	1/68 (1.5%)	1	0/67 (0%)	0
Phlebitis	0/68 (0%)	0	1/67 (1.5%)	1
Vena cava thrombosis	1/68 (1.5%)	1	0/67 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo + Atezolizumab		Tiragolumab + Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/68 (85.3%)		60/67 (89.6%)
Blood and lymphatic system disorders
Anaemia	4/68 (5.9%)	4	7/67 (10.4%)	7
Endocrine disorders
Hypothyroidism	4/68 (5.9%)	4	4/67 (6%)	4
Gastrointestinal disorders
Abdominal pain	3/68 (4.4%)	6	4/67 (6%)	5
Constipation	9/68 (13.2%)	9	9/67 (13.4%)	9
Diarrhoea	10/68 (14.7%)	11	9/67 (13.4%)	12
Nausea	7/68 (10.3%)	9	4/67 (6%)	4
Vomiting	6/68 (8.8%)	7	4/67 (6%)	5
General disorders
Asthenia	17/68 (25%)	18	17/67 (25.4%)	19
Fatigue	9/68 (13.2%)	9	15/67 (22.4%)	18
Oedema peripheral	3/68 (4.4%)	3	7/67 (10.4%)	10
Pyrexia	9/68 (13.2%)	12	8/67 (11.9%)	9
Infections and infestations
Respiratory tract infection	5/68 (7.4%)	7	2/67 (3%)	2
Upper respiratory tract infection	4/68 (5.9%)	4	5/67 (7.5%)	5
Injury, poisoning and procedural complications
Infusion related reaction	7/68 (10.3%)	17	18/67 (26.9%)	22
Investigations
Alanine aminotransferase increased	6/68 (8.8%)	6	3/67 (4.5%)	3
Amylase increased	2/68 (2.9%)	2	4/67 (6%)	9
Aspartate aminotransferase increased	5/68 (7.4%)	5	5/67 (7.5%)	5
Blood creatinine increased	4/68 (5.9%)	4	1/67 (1.5%)	2
Lipase increased	2/68 (2.9%)	2	4/67 (6%)	7
Weight decreased	3/68 (4.4%)	3	4/67 (6%)	4
Metabolism and nutrition disorders
Decreased appetite	12/68 (17.6%)	12	11/67 (16.4%)	11
Hypercalcaemia	4/68 (5.9%)	4	0/67 (0%)	0
Hypokalaemia	1/68 (1.5%)	1	4/67 (6%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	6/68 (8.8%)	7	11/67 (16.4%)	14
Back pain	2/68 (2.9%)	2	6/67 (9%)	6
Musculoskeletal chest pain	4/68 (5.9%)	4	2/67 (3%)	2
Musculoskeletal pain	6/68 (8.8%)	7	4/67 (6%)	4
Myalgia	4/68 (5.9%)	4	3/67 (4.5%)	3
Pain in extremity	2/68 (2.9%)	2	5/67 (7.5%)	5
Nervous system disorders
Dizziness	2/68 (2.9%)	2	5/67 (7.5%)	5
Headache	5/68 (7.4%)	5	4/67 (6%)	5
Psychiatric disorders
Insomnia	4/68 (5.9%)	4	6/67 (9%)	6
Respiratory, thoracic and mediastinal disorders
Cough	7/68 (10.3%)	8	6/67 (9%)	6
Dyspnoea	13/68 (19.1%)	15	9/67 (13.4%)	10
Haemoptysis	5/68 (7.4%)	5	5/67 (7.5%)	6
Productive cough	7/68 (10.3%)	7	3/67 (4.5%)	3
Rhinorrhoea	5/68 (7.4%)	6	4/67 (6%)	4
Skin and subcutaneous tissue disorders
Pruritus	8/68 (11.8%)	12	13/67 (19.4%)	13
Rash	6/68 (8.8%)	7	13/67 (19.4%)	14
Rash maculo-papular	1/68 (1.5%)	1	6/67 (9%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.