A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Adjuvant Platinum-Doublet Chemotherapy, With or Without Atezolizumab, in Patients Who Are ctDNA Positive After Complete Surgical Resection of Stage IB to Select IIIB Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Carcinoma, Non-Small Cell Lung
- Sponsor
- Hoffmann-La Roche
- Primary Endpoint
- ctDNA Clearance Rate at 6 Months
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase II, multicenter, double-blind, randomized study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab in combination with platinum-doublet chemotherapy followed by atezolizumab compared with adjuvant placebo in combination with platinum-doublet chemotherapy followed by placebo in patients with Stage IB to IIIB (T3N2) NSCLC following surgical resection who are positive for ctDNA.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Complete resection (R0) and pathologically confirmed Stage IB to select IIIB NSCLC (8th edition)
- •Submission of pre-surgery blood sample and surgically resected tumor tissue slides or block
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Normal life expectancy excluding lung cancer mortality risk
- •Positive ctDNA status in plasma confirmed by central laboratory testing after surgical resection and prior to start of adjuvant therapy.
Exclusion Criteria
- •Resected NSCLC with positive margins (R1 or R2)
- •NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma
- •Mixed NSCLC and SCLC histology
- •Any prior therapy for lung cancer, including neoadjuvant therapy, or radiotherapy
- •NSCLC with an activating EGFR mutation or ALK fusion oncogene
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Arms & Interventions
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Paclitaxel
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Atezolizumab
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Carboplatin
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Cisplatin
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Pemetrexed
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Gemcitabine
Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance
Intervention: Paclitaxel
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Placebo
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Carboplatin
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Cisplatin
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Pemetrexed
Arm B: Placebo + platinum-doublet followed by placebo maintenance
Intervention: Gemcitabine
Outcomes
Primary Outcomes
ctDNA Clearance Rate at 6 Months
Time Frame: Randomization up to 6 months
ctDNA clearance rate at 6 months after randomization, defined as the proportion of participants with undetectable ctDNA at 6 months in the post-operative ctDNA+ participants.
Disease-Free Survival (DFS)
Time Frame: Randomization up to approximatly 159 months
Disease-free survival (DFS), as assessed by the investigator, and defined as the time from randomization to the date of occurrence of any of the following, whichever occurs first: First documented local or distant recurrence of non-small cell lung cancer (NSCLC) after an integrated assessment of radiographic data, biopsy sample results (if available), and clinical status; Occurrence of new primary NSCLC (non-small cell lung cancer); Death from any cause in the post-operative ctDNA+ participants
Secondary Outcomes
- ctDNA Clearance Rate at 12 Months(Randomization up to 12 months)
- Overall ctDNA Clearance Rate(Randomization up to approximately 159 months)
- Duration of ctDNA Clearance(Up to approximatly 159 months)
- DFS Rate(Randomization to 2 years and 3 years)
- Percentage of Pariticipants with Adverse Events(Randomization up to approximatly 159 months)
- Overall ctDNA Clearance Rate in the PD-L1 TC>=1% Population(Randomization up to approximately 159 months)
- Overall survival (OS)(Randomization to death from any cause (up to approximately 159 months))
- OS Rate(Randomization to 2 years and 3 years)
- Time to Confirmed Deterioration (TTCD) in Patient-Reported Functioning and Global Health (GHS)/Quality of Life (QoL)(Up to approximately 159 months)