A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)

Hoffmann-La Roche453 enrolled

Overview

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

453

Conditions

Non-Small-Cell Lung

Interventions

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab will be administered as intravenous (IV) infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle (every 3 weeks) for 4 cycles during the neoadjuvant treatment phase Atezolizumab will be administered as IV infusion at a dose of 1200 milligrams (mg) every 3 weeks for 16 cycles during the post-operative adjuvant phase

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the AJCC/UICC staging system * Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent * Adequate pulmonary and cardiac function to undergo surgical resection * Measurable disease as defined by RECIST v1.1 * Adequate hematologic and end organ function * Negative HIV test at screening * Negative for active HBV and HCV at screening * Adequate tissue for PD-L1 IHC assessment Exclusion criteria: * NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma * Mixed NSCLC and small cell lung cancer histology * Any prior therapy for lung cancer * Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated expected curative outcome * Non-squamous NSCLC histology with activating ALK and EGFR mutation * Pregnant or lactating women * History of autoimmune disease * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active of active pneumonitis on screening chest Computed Tomography (CT) scan * Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody * Severe infection within 4 weeks prior to randomization * Significant history of cardiovascular disease

Locations (122)

Arizona Oncology

Tucson, Arizona, United States

USC Norris Cancer Center

Los Angeles, California, United States

The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange

Orange, California, United States

UC Davis Cancer Center

Sacramento, California, United States

Scripps Clinic

San Diego, California, United States

Outcomes

Primary Outcomes

Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)

IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.

Time frame: Up to approximately 96 months

Secondary Outcomes

Pathological Complete Response (pCR)

pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor and all sampled lymph nodes as assessed by central and local pathology laboratory.

Time frame: At time of surgery

Major Pathological Response (MPR)

MPR is defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory.

Time frame: At time of surgery

Objective Response (OR)

Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1

Time frame: Prior to surgery, up to approximately 84 days

Overall Survival (OS)

OS is defined as the time from randomization to death from any cause during the course of the study.

Time frame: Up to approximately 96 months

Investigator-Assessed EFS

EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first.

Time frame: Up to approximately 96 months

Disease-Free Survival (DFS)

DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up

Time frame: Up to approximately 96 months

2-Year and 3-Year OS

The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively.

Time frame: Up to approximately 96 months

2-Year and 3-Year Independent Review Facility-Assessed EFS

EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility.

Time frame: Up to approximately 96 months

2-Year and 3-Year Investigator-Assessed EFS

EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator.

Time frame: Up to approximately 96 months

Change from baseline in HRQoL scores

Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments

Time frame: Up to approximately 96 months

Percentage of Participants With Adverse Events (AEs)

Time frame: Up to approximately 96 months

Number and Severity of Surgical Related Adverse Events

Time frame: Up to approximately 96 months

Number of Surgical Delays

Number of surgical delays.

Time frame: Up to approximately 96 months

Length of Surgical Delays

Length of surgical delays.

Time frame: Up to approximately 96 months

Number of Operative and Post-Operative Complications

Number of operative and post-operative complications.

Time frame: Up to approximately 96 months

Reasons for Surgical Cancellations

Reasons for surgical cancellations.

Time frame: Up to approximately 96 months

Minimum Observed Serum Atezolizumab Concentration (Cmin)

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Time frame: Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 96 months)

Maximum Observed Serum Atezolizumab Concentration (Cmax)

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Time frame: Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months)

Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab