A Study of Tiragolumab, an Anti-TIGIT Antibody, in Combination with Atezolizumab Compared with Placebo in Combination with Atezolizumab (an Anti-PD-L1 Antibody) in Patients with Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 May 2020 → 30 Dec 2025

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2022-502482-17-00

EudraCT number

2019-002925-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacokinetic

1. To evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the progression-free survival (PFS) and overall survival (OS) in the primary analysis population

Secondary objectives 5

1. 1. To evaluate the efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab on the basis of the Investigator assessed PFS and OS in the secondary analysis population, confirmed objective response rate (ORR), duration of response (DOR), PFS rate at 6 months and 12 months, OS rate at 12 months and 24 months, time to confirmed deterioration and global health status/quality of life
2. 2. To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with placebo plus atezolizumab
3. 3. To characterize pharmacokinetics of tiragolumab and atezolizumab
4. 4. To evaluate the immune response to tiragolumab plus atezolizumab
5. 5. To evaluate the impact of health status utility scores of patients treated with tiragolumab plus atezolizumab compared with placebo plus atezolizumab

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Age ≥ 18 years and Eastern Cooperative Oncology Group Performance Status of 0 or 1.
2. 2. Histologically or cytologically documented locally advanced or recurrent NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic Stage IV non-squamous or squamous NSCLC. No prior systemic treatment for metastatic NSCLC.
3. 3. Tumor PD-L1 expression as determined by PD-L1 IHC assay TPS >= 50% as determined by 22C3 pharmaDx assay TC3 or IC3 as determined by the VENTANA PD-L1 Assay (SP142), or TC >= 50% as determined by the investigational VENTANA PD-L1 CDx Assay (SP263) of tumor tissue.
4. 4. Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
5. 5. Adequate hematologic and end-organ function.

Exclusion criteria 6

1. 1. Known mutation in the EGFR gene or an ALK fusion oncogene.
2. 2. Symptomatic, untreated, or actively progressing central nervous system metastases.
3. 3. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis.
4. 4. History of malignancies other than NSCLC within 5 years, with the exception of malignancies with a negligible risk of metastasis or death treated with expected curative outcome.
5. 5. Positive test result for human immunodeficiency virus (HIV). Active hepatitis B or hepatitis C infection.
6. 6. Treatment with investigational therapy within 28 days prior to initiation of study treatment. Prior treatment with CD137 agonists or immune checkpoint blockade therapies. Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to initiation of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. PFS as determined by the investigator according to RECIST v1.1 in the primary analysis population
2. 2. Overall Survival (OS) in the primary analysis population

Secondary endpoints 13

1. 1. Investigator assessed PFS according to RECIST v1.1 in the secondary analysis population
2. 2. OS in the secondary analysis population
3. 3. Confirmed ORR as determined by the investigator according to RECIST v1.1
4. 4. DOR for patients with confirmed ORR as determined by the investigator according to RECIST v1.1
5. 5. PFS rate at 6 months and 12 months as determined by the investigator according to RECIST v1.1
6. 6. OS rate at 12 months and 24 months
7. 7. Time to confirmed deterioration (TTCD) in patient-reported physical functioning and global health status/quality of life, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer
8. 8. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0
9. 9. Severity for CRS will also be determined according to the ASTCT CRS consensus grading scale
10. 10. Serum concentrations of tiragolumab and atezolizumab at specified timepoints
11. 11. Prevalence of ADAs to tiragolumab at baseline and incidence of ADAs to tiragolumab during the study
12. 12. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study
13. 13. Change in EQ-5D-5L index-based and visual analog scale (VAS) scores at specified timepoints during the study (including post-progression)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel Town

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 7

Locations

8 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 62 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications