A Study of Tiragolumab in Combination with Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients with Previously Untreated Advanced Non-Squamous 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

17 Dec 2020 → 20 Nov 2025

Decision date (initial)

2024-06-07

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

2022-502031-20-00

EudraCT number

2020-002851-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Efficacy

To evaluate the efficacy of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) on the basis of confirmed objective response rate (ORR) and progression-free survival (PFS), as assessed by investigators according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) (Phase 2) and to evaluate the efficacy of Arm A compared with Arm B on the basis of PFS, as determined by the investigator according to RECIST v1.1, and overall survival (OS) (Phase 3)

Secondary objectives 5

1. 1. To evaluate the efficacy of Arm A compared with Arm B on the basis of OS, duration of response (DOR), and time to confirmed deterioration (TTCD) in patient-reported physical functioning and global health status/quality of life (GHS/QoL) (Phase 2)
2. 2. To evaluate the efficacy of Arm A compared with Arm B on the basis of PFS, as determined by an independent review facility according to RECIST v1.1, PFS and OS in patients with PD-L1 expression at TC ≥ 50% and TC ≥ 1% cut-off, PFS rate at 6 months and 12 months, OS rate at 12 months and 24 months, confirmed ORR, DOR, and TTCD in patient-reported physical functioning and GHS/QoL (Phase 3)
3. 3. To evaluate the safety of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin
4. 4. To characterize the pharmacokinetics of tiragolumab and atezolizumab
5. 5. To evaluate the immune response to tiragolumab and atezolizumab

Conditions and MedDRA coding

Non-squamous non-small cell lung cancer (NSCLC)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
2. 2. Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
3. 3. No prior systemic treatment for metastatic non-squamous NSCLC
4. 4. Known tumor PD-L1 status
5. 5. Measurable disease, as defined by RECIST v1.1
6. 6.Negative HIV test and Serology test negative for active hepatitis B virus and active hepatitis C virus at screening

Exclusion criteria 6

1. 1. Patients with NSCLC which harbors a mutation in the EGFR gene or an ALK fusion oncogene
2. 2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
3. 3. Active or history of autoimmune disease or immune deficiency
4. 4. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
5. 5. History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death
6. 6. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4 (CTLA4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)
2. 2. Investigator-Assessed Progression-free survival (PFS) (Phase 2 and Phase 3)
3. 3. Overall survival (Phase 3)

Secondary endpoints 13

1. 1. Overall survival (Phase 2)
2. 2. PFS as determined by an independent review facility (IRF) (Phase 3)
3. 3. PFS and OS in patients with PD L1 expression at TC ≥50% and TC ≥1% cut-off, as determined by central testing with Ventana PD-L1 (SP263) assay (Phase 3)
4. 4. PFS at 6 months and 12 months (Phase 3)
5. 5. OS rate at 12 months and 24 months (Phase 3)
6. 6. Confirmed ORR (Phase 3)
7. 7. Duration of response for patients with a confirmed objective response, defined as the time from first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (Phase 2 and Phase 3)
8. 8. Time to confirmed deterioration (TTCD) in patient-reported physical functioning and global health status/quality of life (GHS/QoL), as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain, as measured through the use of the EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13) (Phase 2 and Phase 3)
9. 9. Percentage of Participants with Adverse Events (AEs) (Phase 2 and Phase 3)
10. 10. Frequency of patients’ response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item EORTC IL46 (Phase 2 and Phase 3)
11. 11. Serum concentrations of tiragolumab and atezolizumab (Phase 2 and Phase 3)
12. 12. Percentage of participants with anti-drug antibodies (ADAs) to tiragolumab (Phase 2 and Phase 3)
13. 13. Percentage of participants with ADAs to atezolizumab (Phase 2 and Phase 3)

Investigational products

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

Test 2

Comparator 1

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 8

Locations

6 EU/EEA countries · 30 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

Summary of results Art. 37(4) CTR

Documents 74 files

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

Application history

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