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.

• Register: EUCTR
• Last refreshed on: 24 August 2021
• Main ID: EUCTR2020-002851-39-BE
• Date of registration: 23/11/2020
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: 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.
• Scientific title: A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 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.
• Date of first enrolment: 02/02/2021
• Target sample size: 200
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002851-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Hong Kong, Italy, Korea, Republic of, New Zealand, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
• No prior systemic treatment for metastatic non-squamous NSCLC
• Known tumor PD-L1 status
• Measurable disease, as defined by RECIST v1.1
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• Serology test negative for active hepatitis B virus or active hepatitis C virus at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
• Patients with NSCLC which harbors a mutation in the EGFR gene or an ALK fusion oncogene
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active peumonitis
• 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
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the patient may receive during the study
• Known targetable c-ROS oncogene 1 (ROS1) or BRAFV600E genomic aberration.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-small cell lung cancer (NSCLC)
MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: tiragolumab
Product Code: RO7092284/F03-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TIRAGOLUMAB
CAS Number: 1918185-84-8
Current Sponsor code: RO7092284
Other descriptive name: MTIG7192A, anti-TIGIT, aTIGIT, PRO400402, 4.1D3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: TECENTRIQ®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A, Anti-PDL1, Anti-PD-L1, aPDL1, PRO#303280
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: Keytruda
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: RO7223188
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Main Objective: • 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).

Primary end point(s): 1. Investigator-Assessed Confirmed Objective Response Rate (ORR)
2. Investigator-Assessed Progression-free survival (PFS).

Timepoint(s) of evaluation of this end point: 1-2. Up to 5 years.

Secondary Objective: • 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 overall survival, duration of response and time to confirmed deterioration in patient-reported physical functioning and global health status/quality of life (GHS/QoL), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain
• To evaluate the safety 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)
• To characterize the pharmacokinetics of tiragolumab and atezolizumab
• To evaluate the immune response to tiragolumab and atezolizumab.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-5. Up to 5 years
6-8. Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation (up to 5 years).

Secondary end point(s): 1. Overall survival
2. 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)
3. 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)
4. Percentage of Participants with Adverse Events (AEs)
5. Frequency of patients’ response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item EORTC IL46
6. Serum concentrations of tiragolumab and atezolizumab
7. Percentage of participants with anti-drug antibodies (ADAs) to tiragolumab
8. Percentage of participants with ADAs to atezolizumab.

Secondary ID(s)

2020-002851-39-DE

NCT04619797

BO42592

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 02/02/2021
Contact: