A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

Hoffmann-La Roche503 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

503

Conditions

Small Cell Lung Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).

Time frame: Baseline until PD or death, whichever occurs first (up to approximately 23 months)

Duration of Overall Survival (OS) in the Global Population

OS is defined as the time from randomization to death from any cause.

Time frame: Baseline until death from any cause (up to approximately 23 months)

Secondary Outcomes

Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.

Time frame: Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first.

Time frame: First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

PFS Rate at 6 Months and at 1 Year in Global Population

PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively.

Time frame: 6 months, 1 year

OS Rate at 1 Year and 2 Years in the Global Population

OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively.

Time frame: 1 year, 2 years

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

TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant.

Time frame: Baseline until deterioration per symptom subscale (up to approximately 23 months)

Percentage of Participants With at Least One Adverse Event in the Global Population

The percentage of participants with at least one adverse event in the global population.

Time frame: Baseline until up to 90 days after end of treatment (up to approximately 49 months)

Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population

The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.

Time frame: Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population

Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.

Time frame: Post-dose Day 1 of Cycle 1 (cycle length = 21 days)

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population

Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.

Time frame: Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)

Plasma Concentration of Carboplatin in the Global Population

Plasma concentration of carboplatin in the Global population.

Time frame: Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

Plasma Concentration of Etoposide in the Global Population

Plasma concentration of etoposide in the Global Population.

Time frame: Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)