Phase 3
N=403
A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
Small Cell Lung Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02763579 ↗Enrolled (actual)
403
Serious AEs
37.0%
Results posted
Jun 2019
Primary outcome: Primary: Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population — 4.3; 5.2 Months — p=0.0170
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug); Carboplatin (Drug); Etoposide (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population |
4.3; 5.2 | 0.0170 sig |
| PRIMARY Duration of Overall Survival (OS) in the Global Population |
10.3; 12.3 | 0.0069 sig |
| SECONDARY Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population |
76.7; 74.1 | — |
| SECONDARY Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population |
3.1; 4.1 | 0.0063 sig |
| SECONDARY PFS Rate at 6 Months and at 1 Year in Global Population |
22.39; 30.86; 5.35; 12.62 | 0.0593 |
| SECONDARY OS Rate at 1 Year and 2 Years in the Global Population |
38.23; 51.69; NA; NA | 0.0095 sig |
| SECONDARY Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population |
NA; 20.3; NA; NA; NA; NA | 0.3604 |
| SECONDARY Percentage of Participants With at Least One Adverse Event in the Global Population |
96.4; 100.0 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population |
2.0; 18.6 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population |
389 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population |
NA; 80.6; 138; 186; 196; 221 | — |
| SECONDARY Plasma Concentration of Carboplatin in the Global Population |
NA; NA; 13300; 11200; 7200; 6860 | — |
| SECONDARY Plasma Concentration of Etoposide in the Global Population |
NA; NA; 17000; 19400; 11100; 12600 | — |
Summary
This randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin + etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the induction phase followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system)
- No prior systemic treatment for ES-SCLC
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Measurable disease, as defined by 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
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation
- Malignancies other than 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
- Pregnant or lactating women
- History of autoimmune disease
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Positive test result for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
- Severe infections at the time of randomization
- Significant cardiovascular disease
- Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody
- History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation.
Data sourced from ClinicalTrials.gov (NCT02763579). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.