Description:
This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and
etoposide (CE) compared with placebo plus atezolizumab and CE in participants with
chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants
will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1),
LDH (</= upper limit of normal [ULN] vs. > ULN), and presence or history of brain metastasis
(yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment
regimens during induction phase:-
- Arm A: Tiragolumab plus atezolizumab plus CE
- Arm B: Placebo plus atezolizumab plus CE
Following the induction phase, participants will continue maintenance therapy with either
atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).
Title
- Brief Title: A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
- Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
GO41767
- SECONDARY ID:
2019-003301-97
- NCT ID:
NCT04256421
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Tiragolumab | MTIG7192A | Tiragolumab + Atezolizumab + CE |
Atezolizumab | Tecentriq | Placebo + Atezolizumab + CE |
Carboplatin | | Placebo + Atezolizumab + CE |
Etoposide | | Placebo + Atezolizumab + CE |
Placebo | | Placebo + Atezolizumab + CE |
Purpose
This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and
etoposide (CE) compared with placebo plus atezolizumab and CE in participants with
chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants
will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1),
LDH (</= upper limit of normal [ULN] vs. > ULN), and presence or history of brain metastasis
(yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment
regimens during induction phase:-
- Arm A: Tiragolumab plus atezolizumab plus CE
- Arm B: Placebo plus atezolizumab plus CE
Following the induction phase, participants will continue maintenance therapy with either
atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).
Trial Arms
Name | Type | Description | Interventions |
---|
Tiragolumab + Atezolizumab + CE | Experimental | Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. | - Tiragolumab
- Atezolizumab
- Carboplatin
- Etoposide
|
Placebo + Atezolizumab + CE | Active Comparator | Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3. | - Atezolizumab
- Carboplatin
- Etoposide
- Placebo
|
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed extensive-stage small cell lung cancer
(ES-SCLC)
- No prior systemic treatment for ES-SCLC
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST v1.1)
- Adequate hematologic and end-organ function
- Treatment-free for at least 6 months since last chemo/radiotherapy, among those
treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC
Exclusion Criteria:
- Symptomatic or actively progressing central nervous system (CNS) metastases
- Malignancies other than small cell lung cancer (SCLC) within 5 years prior to
randomization, with the exception of those with a negligible risk of metastasis or
death treated with expected curative outcome
- 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 pneumonitis on screening
chest computed tomography (CT) scan
- Positive test result for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
- Severe infection at the time of randomization
- Treatment with any other investigational agent within 28 days prior to initiation of
study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-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 prior to randomization
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Investigator-Assessed Progression Free Survival (PFS) in the Primary Population |
Time Frame: | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | PFS in the Intent-To-Treat (ITT) Population |
Time Frame: | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | OS in the ITT Population |
Time Frame: | From randomization to death from any cause (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed Confirmed Objective Response Rate (ORR) in the Primary Population |
Time Frame: | From randomization up to 50 months |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed Confirmed ORR in the ITT Population |
Time Frame: | From randomization up to 50 months |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed Duration of Response (DOR) in the Primary Population |
Time Frame: | From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first ( up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed DOR in the ITT Population |
Time Frame: | From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first ( up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the Primary Population |
Time Frame: | 6 months, 12 months |
Safety Issue: | |
Description: | |
Measure: | Investigator-Assessed PFS Rates at 6 Months and 12 Months in the ITT Population |
Time Frame: | 6 months, 12 months |
Safety Issue: | |
Description: | |
Measure: | Overall Survival Rates at 12 Months and 24 Months in the Primary Population |
Time Frame: | 12 months, 24 months |
Safety Issue: | |
Description: | |
Measure: | Overall Survival Rates at 12 Months and 24 Months in the ITT Population |
Time Frame: | 12 months, 24 months |
Safety Issue: | |
Description: | |
Measure: | Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the Primary Population |
Time Frame: | From randomization until the first confirmed clinically meaningful deterioration up to 50 months |
Safety Issue: | |
Description: | TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome. |
Measure: | TTCD Assessed Using EORTC QLQ-C30 Score in the ITT Population |
Time Frame: | From randomization until the first confirmed clinically meaningful deterioration up to 50 months |
Safety Issue: | |
Description: | TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome. |
Measure: | Percentage of Participants With Adverse Events |
Time Frame: | Up to 50 months |
Safety Issue: | |
Description: | |
Measure: | Minimum Serum Concentration (Cmin) of Tiragolumab |
Time Frame: | Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 50 months). |
Safety Issue: | |
Description: | |
Measure: | Cmin of Atezolizumab |
Time Frame: | Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Maximum Serum Concentration (Cmax) of Tiragolumab |
Time Frame: | Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Cmax of Atezolizumab |
Time Frame: | Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab |
Time Frame: | Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With ADAs to Atezolizumab |
Time Frame: | Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 12, 2021