Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
- Conditions
- Small Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT04665856
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this multicenter study in China is to evaluate the safety and efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with untreated extensive-stage small cell lung cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 123
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Histologically or cytologically confirmed Extensive-Stage Small Cell Lung Cancer (ES-SCLC) per the modified Veterans Administration Lung Study Group (VALG) staging system
- No prior systemic treatment for ES-SCLC
- For participants who have received prior chemoradiotherapy for limited-stage SCLC must have had treatment with curative intent and a treatment-free interval of at least 6 months between the last dose/cycle of chemotherapy, thoracic radiotherapy, or chemoradiotherapy and the diagnosis of ES-SCLC
- Measurable diseases as defined by RECIST v1.1
- Submission of a pre-treatment tumor tissue sample
- Adequate hematologic and end-organ function
- Participants not receiving therapeutic anticoagulation with International Normalized Ratio (INR) and Activated Clotting Time (aPTT) </= 1.5 x ULN
- Participants receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative Human Immunodeficiency Virus (HIV) test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: negative total hepatitis B core antibody (HBcAb) and/or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test
- Negative Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgM test or negative EBV polymerase chain reaction (PCR) test at screening
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
- Symptomatic or actively progressing central nervous system (CNS) metastases
- Spinal cord compression
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled or symptomatic hypercalcemia
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease, or current alcohol abuse
- Malignancies other than SCLC within 5 years prior to randomization
- Active or history of autoimmune disease or immune deficiencies
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computer Tomography (CT) scan
- Known active tuberculosis, Current treatment with anti-viral therapy for HBV or HCV
- Severe chronic or active infection
- Treatment with therapeutic oral or IV antibiotics
- Significant cardiovascular disease
- Major surgical procedure other than for diagnosis
- Prior allogeneic bone marrow transplantation or solid organ transplant
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition
- Administration of a live, attenuated vaccine
- Prior treatment with CD137 agonists, T-cell co-stimulating, or immune checkpoint blockade therapies
- Treatment with systemic immunostimulatory agents
- Treatment with systemic immunosuppressive medications
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to Chinese Hamster Ovary (CHO) cell products or to any component of the tiragolumab or atezolizumab formulations
- History of allergic reactions to carboplatin or etoposide
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or within 90 days after the final dose of tiragolumab or for 6 months after the final dose of carboplatin or etoposide.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Atezolizumab + Carboplatin and Etoposide Tiragolumab Matching Placebo Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Tiragolumab + Atezolizumab + Carboplatin and Etoposide Tiragolumab Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Placebo + Atezolizumab + Carboplatin and Etoposide Atezolizumab Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Tiragolumab + Atezolizumab + Carboplatin and Etoposide Atezolizumab Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Tiragolumab + Atezolizumab + Carboplatin and Etoposide Carboplatin Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Tiragolumab + Atezolizumab + Carboplatin and Etoposide Etoposide Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Placebo + Atezolizumab + Carboplatin and Etoposide Carboplatin Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Placebo + Atezolizumab + Carboplatin and Etoposide Etoposide Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles
- Primary Outcome Measures
Name Time Method Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS) Up to 32.3 months PFS was defined as time from randomization to the first occurrence of disease progression (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).
Overall Survival (OS) in the PAS Up to 32.3 months OS was defined as the time from the date of randomization to the date of death from any cause.
- Secondary Outcome Measures
Name Time Method Investigator-Assessed DOR in the FAS Up to 32.3 months DOR was defined as the time interval from the date of the first occurrence of a confirmed objective response until the first date of PD as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first. DOR was evaluated for participants who had an objective response of CR or PR. CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS Month 6, Month 12 PFS = time from randomization to the first occurrence of PD, per investigator per RECIST v1.1/ death from any cause, whichever occurs first. PFS rate at 6 and 12 = the percentage of participants who have not experienced PD per investigator per RECIST v1.1/ death from any cause at 6 and 12 months. PD =at least a 20% increase in the sum of diameters of target lesions, taking as reference the SOD at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (K-M) method was used to estimate PFS rate. Percentages have been rounded off. Abbreviation used in Statistical Analysis section - Event Free Rate - EFR. The event free rate (for example the inv-PFS free rate of 10.24% at 12-months) used the K-M approach to estimate, which accounts for the censoring, the specific nature of time-to-event data. Naive calculation based on patient proportion will introduce bias.
Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS Month 6, Month 12 PFS was defined as time from randomization to the first occurrence of PD, as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurs first. PFS rate at 6 months and 12 months defined as the percentage of participants who have not experienced PD as determined by the investigator according to RECIST v1.1 or death from any cause at 6 and 12 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate PFS rate. Percentages have been rounded off. The event free rate used the K-M approach to estimate, which accounts for the censoring, the specific nature of time-to-event data. Naive calculation based on patient proportion will introduce bias.
Overall Survival Rate at 12 Months and 24 Months in the PAS Month 12, Month 24 OS was defined as the time from the date of randomization to the date of death from any cause. OS rate at 12 months and 24 months was defined as the percentage of participants who did not experience death from any cause at 12 months and 24 months. Percentages have been rounded off.
Overall Survival Rates at 12 Months and 24 Months in the FAS Month 12, Month 24 OS was defined as the time from the date of randomization to the date of death from any cause. OS rate at 12 months and 24 months was defined as the percentage of participants who did not experience death from any cause at 12 months and 24 months. Percentages have been rounded off.
Percentage of Participants With Adverse Events Up to 66 months An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
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 PAS Up to approximately 66 months TTCD Assessed Using EORTC QLQ-C30 Score in the FAS Up to approximately 66 months Maximum Plasma Concentration (Cmax) of Tiragolumab Cycle 1 Day 1, 30 mins post end of infusion (EOI) (cycle length= 21 days) Only sparse pharmacokinetic samples were collected in this study. With the focus on only Cmax and Cmin, there are no additional PK timepoints not reported
Minimum Plasma Concentration (Cmin) of Tiragolumab Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days) Cmax of Atezolizumab Cycle 1 Day 1, 30 mins post EOI (cycle length= 21 days) Cmin of Atezolizumab Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days) Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 49 months) Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS Up to 32.3 months ORR was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart as assessed by investigator according to RECIST v.1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters in the absence of CR. Percentages have been rounded off.
PFS in the FAS Up to 32.3 months PFS was defined as time from randomization to the first occurrence of PD, as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
OS in the FAS Up to 32.3 months OS was defined as the time from the date of randomization to the date of death from any cause.
Investigator-Assessed Confirmed ORR in the FAS Up to 32.3 months ORR was defined as the percentage of participants with either a confirmed CR or PR on two consecutive occasions ≥4 weeks apart as assessed by investigator according to RECIST v.1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters in the absence of CR. Percentages have been rounded off.
Investigator-Assessed Duration of Response (DOR) in the PAS Up to 32.3 months DOR was defined as the time interval from the date of the first occurrence of a confirmed objective response until the first date of PD as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first. DOR was evaluated for participants who had an objective response of CR or PR. CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Trial Locations
- Locations (16)
Beijing Cancer Hospital
🇨🇳Beijing, China
Beijing Chest Hospital
🇨🇳Beijing, China
the First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, China
the First Hospital of Jilin University
🇨🇳Changchun, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The 1st Affiliated Hospital of Nanchang Unversity
🇨🇳Nanchang, China
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