NCT03456063

Completed

Phase 3

A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Hoffmann-La Roche119 sites in 7 countries453 target enrollmentApril 24, 2018

InterventionsAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Nab-paclitaxel Pemetrexed Carboplatin Cisplatin Gemcitabine Placebo Comparator

DrugsAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Placebo Comparator Nab-paclitaxel Pemetrexed Carboplatin Cisplatin Gemcitabine

Overview

Phase: Phase 3
Intervention: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Conditions: Non-Small-Cell Lung
Sponsor: Hoffmann-La Roche
Enrollment: 453
Locations: 119
Primary Endpoint: Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

April 24, 2018

End Date

December 31, 2025

Last Updated

3 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Arm A: Atezolizumab + platinum-based chemotherapy

Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab

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

Arm A: Atezolizumab + platinum-based chemotherapy

Intervention: Nab-paclitaxel

Arm A: Atezolizumab + platinum-based chemotherapy

Intervention: Pemetrexed

Arm A: Atezolizumab + platinum-based chemotherapy

Intervention: Carboplatin

Arm A: Atezolizumab + platinum-based chemotherapy

Intervention: Cisplatin

Arm A: Atezolizumab + platinum-based chemotherapy

Intervention: Gemcitabine

Arm B: Placebo + platinum-based chemotherapy

Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery

Intervention: Placebo Comparator

Arm B: Placebo + platinum-based chemotherapy

Intervention: Nab-paclitaxel

Arm B: Placebo + platinum-based chemotherapy

Intervention: Pemetrexed

Arm B: Placebo + platinum-based chemotherapy

Intervention: Carboplatin

Arm B: Placebo + platinum-based chemotherapy

Intervention: Cisplatin

Arm B: Placebo + platinum-based chemotherapy

Intervention: Gemcitabine

Outcomes

Primary Outcomes

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

Time Frame: Up to approximately 96 months

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.

Secondary Outcomes

Objective Response (OR)(Prior to surgery, up to approximately 84 days)
Length of Surgical Delays(Up to approximately 96 months)
Investigator-Assessed EFS(Up to approximately 96 months)
2-Year and 3-Year OS(Up to approximately 96 months)
Change from baseline in HRQoL scores(Up to approximately 96 months)
Percentage of Participants With Adverse Events (AEs)(Up to approximately 96 months)
Number and Severity of Surgical Related Adverse Events(Up to approximately 96 months)
Number of Surgical Delays(Up to approximately 96 months)
Maximum Observed Serum Atezolizumab Concentration (Cmax)(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))
Pathological Complete Response (pCR)(At time of surgery)
Major Pathological Response (MPR)(At time of surgery)
Overall Survival (OS)(Up to approximately 96 months)
Disease-Free Survival (DFS)(Up to approximately 96 months)
2-Year and 3-Year Independent Review Facility-Assessed EFS(Up to approximately 96 months)
2-Year and 3-Year Investigator-Assessed EFS(Up to approximately 96 months)
Number of Operative and Post-Operative Complications(Up to approximately 96 months)
Reasons for Surgical Cancellations(Up to approximately 96 months)
Minimum Observed Serum Atezolizumab Concentration (Cmin)(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))
Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab(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))