A clinical study comparing Tiragolumab plus Atezolizumab and chemotherapy with Pembrolizumab and chemotherapy in patients with untreated advanced non-small cell lung cancer
Descrizione riassuntiva dello studio
The aim of this study is to compare the positive and negative effects of Tiragolumab plus Atezolizumab (Tecentriq®) plus chemotherapy with those of placebo plus Pembrolizumab (Keytruda®) and chemotherapy in patients with NSCLC. In this study, the participant receives either Tiragolumab plus Tecentriq® plus chemotherapy (Group A) or placebo plus Keytruda® and chemotherapy (Group B). This is a ‘placebo-controlled’ clinical study, meaning that one of the groups receives a drug without active ingredients (a so-called ‘placebo’). A placebo is used to show that the doctor or the patients do not influence the study results. Neither the patient nor the investigator knows the treatment group or can choose it. However, the investigator can find out which group a patient is in if safety is at risk. All study participants are randomly assigned (like flipping a coin) to one of the two treatment groups. The probability that the patient is assigned to one group or the other is equal. Both groups start the study with the ‘induction phase’ and then continue after 3 months with the ‘maintenance phase’. A total of 300 patients are expected to participate in this study, about 20 of them in Switzerland.
(BASEC)
Intervento studiato
The combination therapy of Tecentriq®, Tiragolumab, and chemotherapy will be compared to the combination therapy of Keytruda®, placebo, and chemotherapy. Tiragolumab is an antibody (a protein produced by the body's immune system) that blocks a specific signaling pathway (TIGIT signaling pathway), which is important for camouflaging cancer cells from the immune system. Thus, Tiragolumab may help enhance the immune system and stop or reverse tumor growth. Tiragolumab is not yet approved by health authorities. Tecentriq®, like Keytruda®, also antibodies, enable the destruction of cancer cells by the immune system through their immune-stimulating effect. Tecentriq® is approved in combination with chemotherapy and Keytruda® is approved in combination with chemotherapy by health authorities worldwide for the treatment of patients with NSCLC. Pemetrexed, Cisplatin, and Carboplatin are chemotherapeutics that are routinely used in the treatment of lung cancer. The specific combination of Tiragolumab in combination with Tecentriq® and chemotherapy is experimental. This means that these combinations have not yet been approved by any health authority for the treatment of cancer or any other disease. It is believed that the combination of these three agents (Tecentriq®, Tiragolumab, and chemotherapy) may enhance anti-cancer activity due to the complementary mechanisms of action of each agent. The study consists of an ‘induction phase’ and a ‘maintenance phase’. In the induction phase, patients in each group receive the following treatments every 3 weeks over 4 treatment cycles: ● Group A: Tecentriq®, administered as an intravenous infusion, followed by Tiragolumab, administered as an intravenous infusion, followed by chemotherapy (first Pemetrexed and then either Carboplatin or Cisplatin, both administered as intravenous infusions) ● Group B: Keytruda®, administered as an intravenous infusion, followed by placebo, administered as an intravenous infusion, followed by chemotherapy (first Pemetrexed and then either Carboplatin or Cisplatin, both administered as intravenous infusions). After the induction phase is complete, patients begin the maintenance phase. In this part of the study, patients in both groups no longer receive Carboplatin or Cisplatin during chemotherapy. However, all other treatments remain the same: ● Group A: Tecentriq®, administered as an intravenous infusion, followed by Tiragolumab, administered as an intravenous infusion, followed by chemotherapy (Pemetrexed, administered as an intravenous infusion) ● Group B: Keytruda®, administered as an intravenous infusion, followed by placebo, administered as an intravenous infusion, followed by chemotherapy (Pemetrexed, administered as an intravenous infusion). The status of the cancer will be checked approximately every 11 months every 6 weeks and then every 9 weeks. Patients continue to receive the study treatment as long as the cancer does not worsen or your doctor decides that continuing treatment does not provide any benefit to the participants. All participants are free to discontinue this treatment at any time. After the last dose, the doctor will follow up with the patients approximately every 3 months in the hospital or by phone as long as they agree.
(BASEC)
Malattie studiate
A ‘non-small cell lung cancer’ or NSCLC, which is locally advanced (i.e., it has spread in the lung and to the lymph nodes in the middle chest area), inoperable (i.e., it cannot be surgically removed) and has not been previously treated.
(BASEC)
You can participate in this study if you have been diagnosed with locally advanced, inoperable, or metastatic NSCLC. • You must not have received any medications for the treatment of advanced NSCLC prior • You must not have tumors with a mutation in the EGFR or ALK gene (EGFR = epidermal growth factor, ALK = anaplastic lymphoma kinase) • If you received treatment for a previous diagnosis of NSCLC, it must have been at least 12 months ago. (BASEC)
Criteri di esclusione
You cannot participate in this study if any of the following criteria apply to you: • You have tumors with a mutation in the EGFR or ALK gene • You have central nervous system metastases • You have been diagnosed with an active or previous autoimmune disease or immunodeficiencies. (BASEC)
Luogo dello studio
Aarau, Chur, Zurigo
(BASEC)
Sponsor
NA
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Clinical Trials
+41 61 715 43 91
switzerland.clinical-research@clutterroche.comRoche Pharma (Schweiz) AG
(BASEC)
Informazioni generali
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
switzerland.clinical-research@clutterroche.com(ICTRP)
Informazioni scientifiche
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
switzerland.clinical-research@clutterroche.com(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
17.11.2020
(BASEC)
ID di studio ICTRP
EUCTR2020-002851-39 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A PHASE II/III, 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 PREVIOUS (BASEC)
Titolo accademico
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. - NA (ICTRP)
Titolo pubblico
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. (ICTRP)
Malattie studiate
Non-small cell lung cancer (NSCLC)
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervento studiato
Trade Name: Pemetrexed
Product Name: Pemetrexed
Product Code: [NA]
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: PEMETREXED
CAS Number: 137281-23-3
Current Sponsor code: NA
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 500-
Trade Name: CISPLATINO TEVA ITALIA - 1MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 100 ML
Product Name: Cisplatin
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: CISPLATIN
Current Sponsor code: NA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Trade Name: CARBOPLATINO AHCL - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 15 ML
Product Name: Carboplatin
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: CARBOPLATINO
Current Sponsor code: NA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
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
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?
Product Name: Atezolizumab
Product Code: [RO5541267]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal (ICTRP)
Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)
Disegno dello studio
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 (ICTRP)
Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes
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
? 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
(ICTRP)
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.
Endpoint primari e secondari
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).;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.;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. (ICTRP)
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 (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.;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). (ICTRP)
Data di registrazione
20.05.2021 (ICTRP)
Inclusione del primo partecipante
22.12.2020 (ICTRP)
Sponsor secondari
non disponibile
Contatti aggiuntivi
Trial Information Support Line-TISL, global.rochegenentechtrials@roche.com, Genentech Inc. c/o F. Hoffmann-La Roche Ltd (ICTRP)
ID secondari
BO42592, 2020-002851-39-DE (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002851-39 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile